Introduction

Cancer is a formidable worldwide health concern and remains a substantial contributor to worldwide mortality. Cancer can be defined as the uncontrolled division or growth of cells that can easily evade and destroy their surroundings and can also spread to other parts of the body. The grim statistics on cancer-related deaths underscore its profound impact on individuals and societies. According to the 2020 report from the World Health Organization’s Global Cancer Observatory, malignancies hold the unenviable position of being the foremost cause of global mortality. Carcinoma cells, responsible for this devastating disease, exhibit marked morphological abnormalities, including pleomorphism, loss of cellular polarity, and anaplasia, characteristics that enable their aggressive spread to distant anatomical sites.1 More than 200 distinct cancer forms have been identified worldwide to date. The WHO projects a worrisome 25% increase in cancer-related fatalities from 2020 to 2030, underscoring the pressing need for effective prevention and treatment strategies.2 Despite advancements in medical science, cancer remains an imposing challenge and continues to be one of the world’s most deadly diseases, casting a heavy burden on both individuals and communities.3

It is possible to treat early-stage cancers surgically, but it is challenging to eradicate all neoplasms through surgery alone. In most cases, adjunctive therapies such as chemotherapy or radiotherapy are indispensable.1 The primary strategy for achieving a cure lies in the early diagnosis of cancer, a task facilitated through various diagnostic modalities, including X-ray,4 Endoscopy,2 Colonoscopy, Ultrasonography, Blood Serum analysis, etc.5 Despite advancements in therapeutic agents over the decades, issues persist with their non-targeted distribution throughout the body. This inherent lack of precise targeting, limited bioavailability, rapid excretion, and substantial toxicity necessitate the administration of high dosages to attain the desired therapeutic concentration at the intended site.6 Consequently, refining drug delivery mechanisms to facilitate specificity and reduce adverse effects remains a critical focus in oncological research.7 In this regard, due to their site-specific delivery and biomimetic nature, biomimetic nanoparticles have recently garnered significant interest in cancer therapy. Over the past few decades, these nanoparticles (NPs) have undergone substantial cutting-edge research, especially for cancer, trauma, cardiovascular disease, acute kidney injury, rheumatoid arthritis, etc. NPs are tiny particles that range between 1 and 100 nm.8 Biomimetic nanoparticles are a novel frontier in the fight against cancer. These nanoparticles were meticulously crafted to mimic the complex operations of biological systems, adopting nature’s elegance as their primary design influence. Biomimetic nanoparticles hold the potential to make cancer therapy a more targeted and successful attempt by mimicking physiological processes, including cell targeting and drug transport.1 The latest methods for preparing biomimetic materials include 3D printing, electrospinning, biological templating, and surface coating.9 These preparation processes aim to mimic the functional and biological properties. Recent progress focuses on advanced fabrication of these biomimetic nanomaterials for tissue engineering, drug delivery, and the development of scaffolds.10 The development of these methods focuses on multi-scale design of nanostructures and integration with native cells or tissues for specific applications.

The limitations of conventional therapies, such as rapid clearance by the immune system and poor drug targeting, can be overcome by using new technologies.11 And one of them includes the use of cellular components to mimic the natural cellular structures. Biomimicking offers improved biocompatibility and reduced toxicity, which allows efficient drug delivery to disease-specific targeted sites.12 Immune evasion provides an extended circulation time and allows the biomimetic nanoparticles to reach the target site.13 The surface modification with the cell membrane enables the nanoparticle to mimic the self-recognition on the cell surface, leading to more precise drug delivery, and a similar biostructure also makes the biomimetic nanoparticles more compatible with biological systems and reduces the potential toxic side effects associated with conventional nanoparticles.14 These abilities provide a significant enhancement in the therapeutic efficacy of the drug carrier and overcome biological barriers. Biomimetic nanoparticles act as an interlink between the synthetic materials and the complex biological environment, making a sophisticated mechanism for the development of a particular and compelling drug delivery system.15

Thus, biomimetic nanoparticles offer a diverse array of applications, including targeted drug delivery, photothermal therapy, gene delivery, antimicrobial treatments, vaccines, tissue engineering, and the monitoring of the phenotypic evolution of cancer cells, all while minimizing undesirable immune responses.16 One of the key strategies in developing these nanoparticles involves camouflaging them with cell membranes, which opens innovative avenues for research. Red blood cell-coated nanoparticles, for instance, exhibit an improved half-life. This biomimetic approach allows nanoparticles to evade the immune system’s surveillance and effectively express their targeting properties. Additionally, surfaces engineered with nanoparticles that have natural ligands or plasma membranes obtained from cancer cells significantly improve drug specificity by attaching to specific biological markers on the surface of cancer cells (Figure 1). However, challenges like robust clinical translation and ensuring biocompatibility of purified cell membranes for clinical application remain unresolved.17

Figure 1 Schematic illustration of a biomimetic nanoparticle encapsulated antineoplastic agent and its surface functionalization for targeting cancer cells to site-specific cargo release.

This review explores the nature of biomimetic nanoparticles, how they revolutionize cancer therapy by mimicking biological activities, and provides targeting and immunomodulatory strategies. Exploring the latest advancements in biomimetic nanoparticles synthesized from natural cells and shedding light on their potential in cancer therapy management. The collaborative information about the basics and recent development of biomimetic nanoparticles, their immune response, and their clinical translation in cancer treatment and diagnosis will help the researchers, scientists and young individuals to exploit the advanced developments of this field. This review also offers an insight into how these innovative technologies may reshape the landscape of cancer treatment, providing more targeted and effective therapeutic options.

Cancer: Development, Immune Response and Its Clinical Aspects Development of Cancer Cells

The disease of cancer is characterised by abnormal cell proliferation with the ability to infiltrate or spread to other sections of the body.5 Symptoms include unusual bleeding, a persistent cough, a lump, weight loss, and a change in bowel habits, which should be investigated promptly.18 The hormones or other chemicals released by the tumor cause some systemic symptoms of cancer, like paraneoplastic disorder, which consists of hypercalcemia, causing altered mental status, constipation, dehydration, and hyponatremia, causing altered mental status along with headache and seizures. The process by which the cancer cells migrate to different body parts is called metastasis. A metastatic tumor is a cancer that has migrated beyond its original location, whereas a primary tumor is a cancer that has not spread to other parts of the body.6 The immune cells of the body, such as CD8+ T cells and natural killer cells, identify the tumor cells in the initial stage and fight to eliminate them from the body.19 While the others, such as macrophages, neutrophils, and B cells, not only help to counter the tumor progression but also support and promote its growth. With this, tumor cells can also escape the immune response by avoiding immunorecognition and initiating an immune-suppressive tumor microenvironment (TME).19

The uncontrolled growth of cancer cells leads to a proliferation of irregularities that disrupt various cellular regulatory mechanisms, adversely impacting the patient’s immune system.7 Cancer treatments, such as chemotherapy and radiation therapy, can harm the bone marrow, leading to a reduction in blood cell production. Consequently, the immune system becomes weaker, and the body is less able to fight infections. The origin of cancer comprises both the disease itself and the external agents that induce disruptions within the body. The precise cause of cancer is still unknown, even after years of research. However, new developments in cytogenetics and molecular biology give hope that the underlying causes of cancer may eventually be understood. The second component of cancer causation is challenging to understand and involves a complex interaction of variables that are related to the growth of human cancer. Ionizing radiation stands out as one of the most widely recognized causes of cancer in humans. Notably, ionizing radiation emerges as a prominently acknowledged contributor to cancer in humans among these factors.

Immune Response

Cancer cells can spread out from where they started, infiltrating neighboring tissues and developing masses at other parts of the body, known as tumors. Tumors are particularly dangerous when the tissues and organs essential for the organism’s overall survival are damaged. In genetically altered cells, tumors form when a single cell within a healthy population has a genetic mutation that enhances its proclivity to multiply when it should be resting. In hyperplasia, the altered cell and its descendants appear normal, but they reproduce excessively. After years, one in a million of these cells suffers another mutation that further loosens controls on cell growth. The abnormal growth of cells is said to be malignant when genetic changes allow it to invade underlying tissue and shed cells into the blood or lymph. Cancer also weakens our immune system, which is crucial for fighting cancer. It spreads into the bone marrow and reduces the amount of blood cells (mainly in leukaemia or lymphoma), thus weakening the immunity to eradicate the cancer cells.20 Sometimes, the cancer treatment itself temporarily affects the immune system, which also includes some immunotherapies like monoclonal antibodies, vaccines, cytokines, and CAR T-cell therapy.20 Burnet and Thomas gave the immunological surveillance theory, suggesting the recognition of malignant cells by assessing the presence of tumor-associated antigens or tumor-specific antigens.21 But these cancer cells learned and adapted to survive by evading the immune system. Indoleamine 2,3-dioxygenase, an immunomodulatory enzyme, is a significant factor in malignant cell growth and immune suppression. Inhibiting this enzyme may overcome the effects of traditional chemotherapeutic treatments. Immunity not only helps to eradicate the cancer development or proliferation but also enhances its progression in some cases, eg, Chronic gastritis caused by Helicobacter pylori can be associated with gastric cancer.21 Thus, failure in the elimination of a foreign substance may further lead to malignant progression and cancer expansion.

Clinical Aspects

Cancer treatment encompasses a multifaceted range of clinical approaches, including advanced diagnostic techniques, standardized staging systems, diverse treatment procedures, and comprehensive patient care. Continuous evolution in cancer’s clinical management emphasizes multidisciplinary collaboration, precise medication, and patient-centred support services to optimize the treatment outcomes. Diagnostic approaches, such as biomarker identification and imaging technology, involve the detection of genetic mutations, protein levels, and circulating tumor DNA (ctDNA), which provides valuable information to identify malignancies at various stages. Several traditional and novel biomarkers expanded the capabilities of tumor diagnosis. Traditional tumor marker examples include AFP, PSA, CA-125, and CEA markers for liver, prostate, ovarian, and colorectal cancer, respectively.22 Whereas microRNA, synthetic biomarkers, circulating nucleosomes, and tumor cells are examples of novel biomarkers.23

Standardized staging systems, primarily the TNM system, can help to guide the prognosis and treatment of tumors. The TNM staging system is an internationally accepted standard for the classification of cancer, regulated by the American Joint Committee on Cancer and the Union for International Cancer Control.24 T describes the primary tumor size and local tissue invasion, N indicates the involvement of lymph nodes, and M determines the distant metastatic spread. The TNM classification collaboratively describes the overall cancer stages from 0 to IV.25 Furthermore, the treatment procedures and clinical approaches include surgery, chemotherapy, radiation, targeted therapy, and immunotherapy, depending on cancer type, stage, and patient-related factors.26 Modern surgical approaches involve the removal of the tumor with minimal invasive techniques.27 Advances in chemotherapy focus on improving side effects, including nausea, fatigue, hair loss, and immunosuppression, with optimized drug combinations.28 And, radiation therapy for tumor shrinkage before surgery and sometimes post-operatively to eliminate the residual cancer cells.29 Still, with such effective available treatment options, more precise, safer, and patient-oriented advanced therapies are needed. Targeted therapy, immunotherapy, and combination therapies are some of the most recently used advanced techniques.30 Unlike chemotherapy’s broad cellular effect, targeted therapy offers the use of a specific drug targeting a specific molecular pathway to inhibit cancer cell survival.4 Thus, offering a personalized treatment with potentially reduced side effects. Immunotherapy boosts the patient’s immune system against cancer, and recent clinical trials also demonstrate improvements in cancer patients with 67% shrinkage in metastatic non-small cell lung cancer, better than 50% shrinkage with standard therapy.31 Another example showed that pembrolizumab immunotherapy after bowel cancer surgery eliminates the signs of cancer in over 50% of patients.32 And, combination therapies mean the integrated use of multiple treatment procedures instead of relying on a single approach to maximize the therapeutic efficacy while managing the toxic profile of therapies.33

Participation in cancer treatment trials has improved, with 7.1% of cancer patients enrolling in treatment trials. However, NCI-designated cancer centres alone achieved 21.6% enrolments, while only 4.1% enrolments were achieved by community programs.34 Overall, 21.9% of cancer patients participate in at least one or more clinical research study, contributing 12.9% in biorepository studies, 7.3% in registry studies, 3.6% in genetic studies, and 2.8% in quality of life research studies.34 Active participation of physicians and availability of digital platforms can serve as a streamlined tool for identification and acceleration of clinical trial recruitment. Studies also demonstrated that around 73% of cancer patients learn about clinical trial opportunities through their physician or healthcare provider.35 Cancer survivors also experience some of its long-term effects that include persistent fatigue, chronic pain, musculoskeletal problems, cognitive dysfunction, depression, and fear of recurrence.36 These long-term survival challenges present physical and psychosocial effects even after the completion of treatment. Studies showed that breast cancer survivors experience the lowest functioning levels, which hampers their quality of life as compared to prostate cancer survivors, who have high functioning with minimal symptoms.37 Therefore, clinical research is necessary to form and enhance the clinical guidelines, leading to improved patient-centred care, safety, and quality of life.

Biomimetic Nanoparticles

The architecture and functionalities of these NPs are intended to resemble those of real biological entities.38,39 Their application in medicine is quite promising, especially in therapeutic drug delivery systems based on biomimetic nanoparticles. These systems can change how individuals treat and identify illnesses.40 Biomaterials that can replicate the biological characteristics and functions of natural cells are integrated or synthesized into the surface of an emerging class of nanoparticles known as biomimetic nanoparticles.41 They possess a greater biocompatibility, higher site-specific targeting, better bioavailability, and minimal side effects.42 In medicine, the three parts of bionic refer to: Directly extracting, isolating, and purifying endogenous chemicals from people, animals, or microorganisms; Creating goods that are comparable to the endogenous substances in terms of their composition and operation; and that resemble the disease’s microenvironment.43 Since they are more effective at targeting and retaining cargo, biomimetic nanoparticles have been used as drug delivery vehicles for many years.44 Whereas, non-targeted cargo can impact healthy cells or organs rather than the desired site.45 In recent times, nanotechnology and nanoscience have been widely applied in biomedical research.46 Due to its ability to resist phagocytosis, it successfully passed as an endogenous molecule and achieved prolonged blood circulation.47 Although nanoparticles have become a promising drug delivery system, there are several factors that hamper their capacity. To overcome them, nanocarriers are being cloaked with different types of cell modifications. It helps the vehicle to bypass the cell membrane and reach the target site. And, for the development of cancer therapy, biomimetic nanoparticles have been proven to be an innovative drug delivery platform for enhancing the drug payload and biocompatibility.48

Developing appropriate carriers is crucial in achieving high targeted efficiency and low overall toxicity.49,50 Enhancing the accumulation of chemotherapeutic agents at the targeted locations can improve therapeutic effectiveness in certain areas and reduce drug resistance.44 To increase the therapeutic efficacy at targeted sites and minimize drug resistance, it is essential to develop suitable carriers that can improve the accumulation of chemotherapy agents at targeted locations.51 Biomimetic nanoparticles, such as cell membrane-coated, RBC-coated, stem cell-coated, and platelet-coated carriers, can help achieve this goal.52 The liposomal drug carrier has also proven to be an effective delivery vehicle. Its phospholipid bilayer can generate a nanostructure that imitates natural cells, but the instability caused by the absence of a fully developed membrane structure continues to be a significant drawback.53 Rather than that, nanoparticles with surface modification by incorporating natural ligands or a cancer-derived plasma membrane significantly increase the drug’s specificity by attaching to specific biological markers found on the membranes of cancer cells.41,53 To date, several nanoparticle-based drugs have been formulated to counter cancer.54–57 Nanotechnology and nanomedicine have a very high scope in biomedical research and applications.43 Nanoparticle-embedded drugs have better affinity to reach the target site and provide therapeutic effects.58 From the literature, it is clear that biomimetic functionalization of nanoparticles and other materials can resolve many biomedical conditions.59 A comparative overview of biomimetic nanoparticulate platforms representing their drug-encapsulation strategies, tumor-targeting features, in vivo models, and therapeutic outcomes is presented in Table 1. Studies have also mentioned that coating nanocarriers with modified membranes helps prolong blood circulation and enhances tumor tissue penetration.38,41,55

Table 1 Comparative Summary of Various Biomimetic Nanoparticulate Platforms, Highlighting Drug Encapsulation Strategies, Tumour-Targeting Properties, in vivo Models and Corresponding Therapeutic Outcomes

Red Blood Cell-Coated Nanoparticles

RBC-coated nanoparticles’ excellent payload efficiency, biocompatibility, deformability, and deterrability make them one of the most potent biomimetic drug carriers.94,95 RBC-membrane camouflaged nanoparticles have been demonstrated to possess a significantly improved capability for evasion from the mononuclear phagocytic system.96 Designing nanoparticles for in vivo medicinal uses requires determining their hemocompatibility.60 This, in turn, enhances the delivery of therapeutics to the tumor location, thereby alleviating systemic undesired effects. And, due to the highly flexible RBC structure, cells can move through relatively small capillary networks, including factors such as cell surface-to-volume ratio, cell content viscosity, and membrane viscoelasticity. Glycocalyx, a thick polysaccharide covering on the surface of RBCs, is crucial for immunological escape properties and cell stability. These complex polysaccharides on the cell surface are comparable to a hydrophilic coating in achieving spatial stability. In contrast, the stabilized RBC-NP surface can effectively block further membrane interactions. Even in the presence of extra RBCs, this stabilizing mechanism ensures the formation of a monolayer film coating. From the literature, it was found that nanoparticles modified with RBC membrane show high affinity towards the specific site and have high drug loading capacity.97 The RBC membrane-coated nanoparticles have an improved half-life, making them a more accepted modification type of cargo vehicles.98 The preparation of RBC camouflaged nanocarriers can be carried out through both physical and chemical methods.41 Firstly, the desired type of nanovesicle is prepared, which is further coated with the RBC membrane.99 The techniques used to carry it out include the cell membrane-templated polymerization, microfluidic electroporation, co-extrusion, etc.

In response to the rising issue of lung metastasis, a group of researchers developed the M@AP nanoplatform to activate immune cells in the spleen, thereby enhancing anti-carcinogenic activity.100 Furthermore, quantitative analysis of M@AP nanoparticles revealed their ability to directly damage local tumor cells and stimulate immune cells to generate cytokines, thereby presenting cellular damage against tumor cells. In B16-F10 tumor-bearing mice, the in vivo anti-tumor activity was examined. The observed levels of CD4 and CD8 in M@AP (Light+) were approximately 40% higher than those of the other groups. Similarly, RBC membrane-coated (TPC-PTX) nanoparticles were synthesized for synergistic chemo- and photodynamic therapy (PDT). It involved a combination of chemotherapy and photodynamic therapy, thereby enhancing anti-cancer therapeutic activity and light-triggered drug release, which reduces systemic toxicity. After 23 hours, it also showed a difference of ~4.6-fold higher absorption when loaded with PTX2-TK.

Moreover, to overcome the barrier of internalization in breast cancer treatment, RBC-4T1@DOX/CS-NPs were prepared and evaluated for cellular toxicity effects and in vitro nanoparticle uptake in cells. The drug loading efficiency of the mentioned nanoparticle was evaluated for doxorubicin (DOX), which showed a positive result of 72–73% loading of the drug. Thus, the prepared nanoparticle showed notable cellular uptake and cellular damage in the 4T1 breast cancer cell line.99 Similarly, molybdenum disulfide nanocomposites-RBC were prepared by another researcher’s group for breast cancer treatment. The in vivo fluorescence imaging and in vivo photothermal imaging test of molybdenum disulfide nanocomposites-RBC nanoparticle confirmed the promoted accumulation of carrier materials at the tumor site after RBC membrane modification. The in vivo analysis also showed that the nanocomposite loaded with Adriamycin hydrochloride/DOX has over 98% drug loading capacity and provided better efficacy.101 Despite having high potential, RBC-coated biomimetic nanoparticles face several challenges. Scalability and reproducibility tend to be the main concerns in the manufacturing of biomimetic nanoparticles.64

Nanoparticles coated with RBC membrane, believed to have very low immunogenicity, may be prone to an immune response.102 By encapsulating porous magnetic biomimetic nanoparticles in salvianolic acid B, researchers developed a biomimetic approach for synergistically targeting triple-negative breast cancer.103 The PMNP-SAB@RTM is prepared through altering the tumor-associated fibroblast membrane and red blood cell membrane (RBCM) (Figure 2A). The maximum encapsulation efficiency rate of SAB was found to be approximately 97.28%, with the mass ratio of 1:2 for SAB to PMNPs. Additionally, in vitro assays on the 4T1 cell line and in vivo studies showed reduced cell viability and the overcoming of tumor-associated physical barriers upon the application of magnetic field, respectively. This enhances drug penetration, increases tumor cell apoptosis and necrosis, and suppresses cell proliferation more effectively than the drug alone, demonstrating strong synergistic antitumor effects.

Figure 2 (A) Schematic representation of the synthesis of PMNP-SAB@RTM. Reproduced with permission from Cheng N, Zhou Q, Jia Z et al. Functionalized biomimetic nanoparticles loaded with salvianolic acid B for synergistic targeted triple-negative breast cancer treatment Material Today Bio.103 Copyright 2025, Elsevier. (B) Illustration of CLSM imaging with DiI labeling nanocarriers (red) and DAPI staining nuclei (blue), scale bar 100μm. Reproduced with permission from Miao Y, Yang Y, Guo L et al. Cell Membrane-Camouflaged Nanocarriers with Biomimetic Deformability of Erythrocytes for Ultralong Circulation and Enhanced Cancer Therapy. ACS Nano.104 Copyright 2022, American Chemical Society. (C) Fluorescence intensity analysis of nanocarrier distribution in tumor 4T1 cells (*** for p<0.001). Reproduced with permission from Miao Y, Yang Y, Guo L et al. Cell Membrane-Camouflaged Nanocarriers with Biomimetic Deformability of Erythrocytes for Ultralong Circulation and Enhanced Cancer Therapy. ACS Nano.104 Copyright 2022, American Chemical Society. (D) Tumor-targeted delivery of Dox and CDDP (cisplatin) via iRGD-TRP-PK1-engineered RBCVs in an HN4 cell-derived xenograft (CDX) model. Reproduced with permission from Bai S, Wang Z, Zhang Yet al iRGD-TRP-PK1-modified red blood cell membrane vesicles as a new chemotherapeutic drug delivery and targeting system in head and neck cancer. Theranostics.105 Copyright 2025, Creative Commons Attribution Non-Commercial License 4.0 (CC BY-NC).

Conventional drug delivery systems have several limitations, including a short systemic circulation time and poor tumor accumulation of conventional nanocarriers used in cancer therapy. Apart from this, most nanocarriers are rapidly cleared from the bloodstream by the mononuclear phagocyte system, which limits their ability to reach tumor sites effectively. Additionally, their rigid structures often hinder their ability to navigate through narrow capillaries and tumor vasculatures. To overcome these limitations, designing a deformable, erythrocyte membrane-camouflaged nanocarrier that mimics the natural flexibility and immune-evasive properties of RBC, can prolong circulation time and improve tumor targeting efficiency. RBC membrane camouflage nanocarriers accelerate circulation and enhance cancer therapy.104 In CLSM findings, RBC membrane-coated elastic poly (ethylene glycol) diacrylate hydrogel nanoparticles displayed a visible fluorescence signal; however, RBC-SNVs and RBC-HNPs only displayed low-level fluorescence in the central tumor area throughout the entire tumor (Figure 2B and C), and very little fluorescence by PEG-Lipo was visible in the tumor tissue’s periphery. The intensity of fluorescence emitted by RBC-ENPs within the tumor showed an approximately 1.8-, 2.4-, and 13.8-fold increase compared with RBC-SNVs, RBC-HNPs, and PEG-Lipo, respectively. Thus, the findings encourage future research to focus on optimizing the deformability and targeting specificity of these biomimetic nanocarriers to enhance their clinical applicability in personalized cancer therapy.104

Recently, RBCVs modified with iRGD-TRP-PK1 were also engineered to function as a targeted vehicle for anticancer drug delivery in head and neck tumors.105 Notably, the RBCVs functionalized with iRGD-TRP-PK1 displayed a characteristic ring-like formation on their outer layer. Following drug encapsulation, noticeable dark spots appeared within the vesicles, indicating successful drug loading. And the loading efficiencies for cisplatin and DOX were found to be 58.63% and 64.34%, respectively. Therapeutic efficacy via in vivo model showed notably higher accumulation of formulation in tumor tissues for all iRGD-TRP-PK1–functionalized vesicle groups compared to controls (Figure 2D), indicating that the DOX or cisplatin-loaded RBCVs conjugated with iRGD-TRP-PK1 have the highest drug targeting ability than other groups. Overall, the iRGD-TRP-PK1-RBCVs represent a significant advancement in targeted chemotherapeutic delivery, offering enhanced efficacy and safety profiles for the treatment of head and neck cancers.

Platelet Membrane-Coated NPs

Platelets exhibit distinct surface moieties responsible for modulating their adhesion to various disease-relevant substrates, involving vascular damage, immune evasion, and pathogen interactions.106 Due to the extensive bio-interfacing properties of platelets, drug carriers that imitate platelets have been created to selectively deliver drug payloads in disease areas for increased therapeutic effectiveness.107 Platelets are essential for hemostasis and wound healing, and their membranes contain a wealth of bioactive molecules that can be capitalized on for therapeutic purposes.108 Platelet membrane-coated nanoparticles tend to possess tumor-homing and circulating tumor cells targeting and metastasis-targeting properties during multiple steps in the metastatic cascade.67 They also possess a variety of surface moieties with broad bio-interfacing capabilities, which are used for targeting various diseased tissues.109 Due to their ability to detect and react to changes in blood flow and endothelial cell disturbance, platelets serve as sentinels of vascular integrity.110 Platelet-membrane-coated nanoparticles have recently been demonstrated to have better biological characteristics than other nanoparticles, as well as to protect nanoparticles against rapid blood clearance and immune system activation.111 When a tissue is injured, platelets quickly create fibrin to clot the bleeding.112 They do act as a temporary scaffold for inflammatory cells, and store cytokines, chemokines, and growth factors that help to initiate the early stages of repair, including the activation of neutrophils functioning as the body’s initial defence mechanism against microbes.113 Indeed, during 12–24 hours of damage, neutrophils make up around 50% of all the cells in the wound, but macrophages take over after 3–5 days.114 The fragmentation of megakaryocytes initiates the biogenesis of platelets, which are enucleated cells. Platelets are currently the focus of numerous research groups worldwide due to their immense potential to alter our fundamental understanding of how various diseases originate. And, due to their involvement during cancer progression, angiogenesis, along with metastasis, platelets are a significant area of study interest in the current scenario.115

Platelet vesicles were used to modify the surface of cuprous oxide nanoparticles with TBP-2 cuproptosis sensitization system (PTC) via the extrusion method.116 This surface modification of PTC, additionally, improves circulation time and cancer targeting, along with the release of copper ions, hydrogen peroxide, and inhibition of copper efflux. This biomimetic PTC system promotes GSH consumption and cell membrane damage through type-1 photodynamic therapy, thereby leading to cuproptosis in tumor cells. In vivo results demonstrated the higher presence, higher growth inhibition and tumor necrosis by the group treated with PCL and light therapy. Also, the group has higher concentration of central memory T cells with minimal or no hepatorenal toxicity.

Direct receptor binding or protein-mediated receptor bridging (such as von Willebrand factor or fibrinogen) are the two ways that platelet-cancer cell interactions can take place. For instance, the C-type lectin-like receptor 2, which binds with podoplanin located at the surface of tumor cells, is a key platelet receptor involved in cancer spread.117 Platelet membrane-coated superparamagnetic oxide nanoparticles loaded with paclitaxel showed a synergistic effect, enhancing cancer treatment through combined chemotherapy and magnetic hyperthermia (Figure 3A).118 The drug release of Paclitaxel loaded SPIONP/PTX/PM was 1.4-fold higher than others at pH 5.5. However, confocal microscopy combined with flow cytometry study findings reveal an increase in uptake of cells in SPION/PTX/PM NPs. Furthermore, Quantitative evaluation of haemolytic activity for various samples, expressed as mean ± SD with three independent measurements (n = 3), indicates that alginate-coated magnetic iron oxide NPs exhibit lower haemolysis than other treated samples (Figure 3B and C). In vivo study findings suggest that the SPION/PTX/PM formulation under AMF treatment revealed the maximum inhibition of tumor growth, which was about 92.14%.

Figure 3 (A) Schematic representation of SPION/PTX/PM NPs using the co-extrusion process. Reproduced with permission from Tavakoli M, Maghsoudian S, Rezaei-Aderiani A et al. Synergistic effects of paclitaxel and platelet-superparamagnetic iron oxide nanoparticles for targeted chemo-hyperthermia therapy against breast cancer. Colloids Surfaces B Biointerfaces.118 Copyright 2025, Elsevier. (B) Mean fluorescent intensity (MFI) of control, SPION NPs, and SPION/PM NPs against MCF-7 cells (** for p<0.01). Reproduced with permission Tavakoli M, Maghsoudian S, Rezaei-Aderiani A et al. Synergistic effects of paclitaxel and platelet-superparamagnetic iron oxide nanoparticles for targeted chemo-hyperthermia therapy against breast cancer. Colloids Surfaces B Biointerfaces.118 Copyright 2025, Elsevier. (C) Quantitative evaluation of hemolysis induced by SPION/PTX/PM NPs, phosphate buffer solution, and Triton X-100 (Positive control) group. Reproduced with permission from Tavakoli M, Maghsoudian S, Rezaei-Aderiani A et al. Synergistic effects of paclitaxel and platelet-superparamagnetic iron oxide nanoparticles for targeted chemo-hyperthermia therapy against breast cancer. Colloids Surfaces B Biointerfaces.118 Copyright 2025, Elsevier. (D) Captured photographs of the tumor dissection of the BALB/c mice model after 14 days. Reproduced with permission from Luo X, Cao J, Yu J et al. Regulating Acidosis and Relieving Hypoxia by Platelet Membrane-Coated Nanoparticle for Enhancing Tumor Chemotherapy. Front Bioeng Biotechnol.69 Copyright 2022, Frontiers. The Authors. (E) TEM imaging of (i) copper-doped nanoparticles (PDA@Cu NPs), (ii) Platelet cell membrane-coated nanoparticles (PC@PDA@Cu NPs). Reproduced with permission from Xin L, Ning S, Wang H, Shi R. Tumor Microenvironment Responsive and Platelet Membrane Coated Polydopamine Nanoparticles for Cancer Radiosensitization by Inducing Cuproptosis Int J Nanomedicine.119 Copyright 2025, The Authors. (F) Elemental composition of PDA@Cu NPs. Reproduced with permission from Xin L, Ning S, Wang H, Shi R. Tumor Microenvironment Responsive and Platelet Membrane Coated Polydopamine Nanoparticles for Cancer Radiosensitization by Inducing Cuproptosis. Int J Nanomedicine.119 Copyright 2025, The Authors.

Addressing the major problems of acidosis and hypoxia in tumors during cancer therapy, a group of scientists formulated an Hb-LOX-DOX-ZIF8 system, camouflaged with platelet membrane nanoparticles, which accelerates chemotherapeutic strategy through modulation of acidosis and alleviation of hypoxia.69 The particle size and zeta potential of ZIF8-based and H-L-D-Z@PM nanoparticles were about 447nm and 964 nm, and 18.7mV and −3.35 mV, respectively. The in vivo study was performed in a 4T1 tumor-induced BALB/c mouse model, and among all treatment groups, the H-L-D-Z@PM nanoparticles-treated group exhibited the smallest tumor size and lowest tumor weight (Figure 3D). Most of these nanoparticles were found within the mononuclear phagocyte system, connected to the phagocyte system (such as the liver and spleen). These observations showed that PM coating significantly increases the tumor accumulation efficiency of H-L-D-Z@PM nanoparticles. The application of lactate oxidase effectively increases oxidative stress and sufficiently reduces intra-tumoral lactate. Meanwhile, used haemoglobin increased the catalytic activity of lactate oxidase, relieved hypoxia, and mediated O2 transport. These nanoparticles had strong biocompatibility and the capacity to actively target tumors due to the coated PM.69

Transmission electron microscopy (TEM) image of PDA@Cu and PDA@Cu/PM revealed that the nanoparticles were spherical, and after coating with platelet membrane, a thin film boundary appeared. The XPS analysis of PDA@Cu validates the presence of Cu, N, and C elements, and these elements are dispersed throughout the NPs (Figure 3E and F).119 Furthermore, antitumor activity was assessed in the 4T1 tumor-bearing mouse model by injecting PCM NPs through the tail vein method. Quantification of copper was measured using ICP-AES, and PC+RT therapy validates that this approach was most efficient among all treatment groups. The amalgamation of Cu + RT leads to severe curoptosis, further accelerates the in vitro immunogenic cell death effect, and enhances dendritic cell maturation. Platelet integrin GPIIb/IIIa, also known as αIIbβ3 integrin, stands out among platelet-cancer cell interactions because it promotes cancer spread through direct and indirect pathways.

Cancer Cell Membrane-Coated Nanoparticles

Modification of nanoparticles using a coating technique via a biological cell is one of the most essential and advanced techniques for targeting a specific cancerous tissue.120 This technique helps in improved targeting when compared to other cell membranes via prolonged systemic circulation and target delivery to the tumor cell.73 On the other hand, immune escape is one of the crucial aspects of these nanoparticles due to the presence of membrane proteins (CD47, E-cadherin, Thomsen-Friedenreich antigens, galectin-3, N-cadherin, and EpCAM). When compared to the other membrane donors, cancer cells can self-target homologous cells, making them robust and straightforward to culture in large numbers.121 Due to the cancer cell membrane coating, nanoparticles can adhere uniformly to early cancer cells, extending their blood circulation and reducing systemic clearance, which further improves tumor targeting.72 Above all, this membrane-coated nanoparticle can target primary tumors and metastatic nodules with the ability of self-recognition within cancer cells.121 Implementation of the biomimetic nanoparticles approach for cancer targeting has revolutionized anticancer therapy, with high therapeutic efficacy, lower toxicity, and relative biosafety.

Many studies have been conducted to advance cancer cell membrane-coated nanoparticles for the efficient delivery of drugs.122–124 Notably, the rise of multidrug resistance in esophageal cancer has negatively impacted the effectiveness of chemotherapy, and this has led to a decreased survival rate of patients. To subdue these issues, a group of researchers developed PEG-TE10@PLGA@DOX-Cur nanoparticles to successfully limit the growth of DOX-resistant esophageal cancer through targeting cells of TE10 and TE10/DOX cells xenografted tumor.73 The solvent evaporation approach was used to synthesize DOX and curcumin-loaded biodegradable poly (lactic-co-glycolic acid) nanoparticles, followed by the addition of TE10 cancerous cell membrane and DSPE-PEG to make them biomimetic nanoparticles. It has been found that the utilization of poly (lactic-co-glycolic acid) as an encapsulating polymer has successfully retarded the leakage of cargo from the membrane. Further, the results of the cytotoxicity study of PLGA@Cur+DOX on TEX10/DOX cells have shown less toxicity, and the cell viability was about 90% when compared to the TE10-PLGA@Cur+DOX and PEG-TE10-PLGA@Cur+DOX nanoparticles. Curcumin and DOX have shown a potent anti-tumor effect when used together in vitro. Additionally, in vivo findings reveal that the anti-tumor effect of PEG-TE10-PLGA@Cur+DOX was better than that of TE10-PLGA@Cur+DOX. This was found to be due to the surface modifications of these nanoparticles with PEG, which results in prolonged blood circulation and prevents their early excretion. On the other hand, the anti-tumor effect of PLGA@Cur+DOX is only better than the control group (p<0.05), indicating the possible use of PLGA in sustained release of cargos.

Similarly, DOX-loaded polylactic glycolic acid nanoparticles were developed through the double emulsion solvent evaporation method to inhibit the development of Hepatocellular carcinoma.70 The results indicated that comparing CC/PLGA/DOX to free DOX, the former showed strong tumor suppression and greater safety. The results showed quick distribution of free DOX throughout the body and elimination within 24 hours. In contrast, DOX, when combined with PLGA/DOX and CC/PLGA/DOX, takes a much longer time for its elimination. In vivo results showed that the anti-tumor effect of free DOX was low when compared to the control group. The tumor reduction rate of PLGA/DOX coating is lower than that of CC/PLGA/DOX, with rates of 20.1% and 52.0%, respectively.

Metformin, an FDA-approved antidiabetic agent, with cancer cell-membrane-coated liposome (TMFL) was used by researchers to inhibit the postoperative recurrence of breast cancer.125 TMFL, under the light irradiation produce singlet oxygen, promotes immunogenic cancer cell death and promotes T cell immunity. The group treated with TMFL and light irradiation during the in vivo study showed the highest inhibition of cancer cells, along with the maturation of dendritic cells to produce a strong anti-cancer immune memory response.

According to the data of Cancer Statistics 2022, the most common cancer in women, accounting for 30% of the total, is breast cancer.126 Although Paclitaxel is a standard treatment for breast cancer, cancer cell membrane nanoparticles can be a good alternative to paclitaxel due to their high hydrophobicity and low tumor selectivity.127 Excellent biocompatibility and built-in targeting modalities of human serum albumin nanoparticles make it an ideal carrier for chemotherapeutic agents.127 4T1 cancer cells were attached with HSA-PTX to enhance their anti-cancer effect and biocompatibility. Compared to HSA-PTX, CM-HSA-PTX exhibited a reduced cell survival rate due to the coating of 4T1 cancer cells. CM-HSA-PTX provides homologous targeting due to its excellent stability in serum, storage, and dilution stability; thus, more PTX might enter the cell and exert its anti-cancer effects.

Another disease is Pancreatic ductal adenocarcinoma, which is one of the most hostile cancers, and the survival rate of 5 years is only 9%.128 Due to the poor treatment outcomes at the progression of the disease and the sensitivity of traditional chemotherapeutic agents, cancer cell membrane nanoparticles are also used for disease treatment. This disease requires ROS-based therapies like photodynamic, chemodynamic, and sonodynamic to overcome the challenges faced through pancreatic ductal adenocarcinoma.129 ROS causes the demise of a cancer cell’s mitochondria by interfering with the electron transport chains.130 The nanoparticle was prepared through the fabrication of core-shell nanoparticles firstly with ZnxMn1-xS (abbreviated as ZMS) and further coated with the pancreatic cancer cell membrane BxPC-3.129 BUC@ZMS core-shell nanostructure has proven to be an efficient therapy for reducing the GSH expression linked to pancreatic ductal adenocarcinoma and showed enhanced blood circulation with a tumor retention effect. It was proposed to work on the principle of ROS accumulation that leads to the death of pancreatic cancer cells, as this therapy for pancreatic ductal adenocarcinoma looks promising. The results of the cytotoxicity study done on BxPC-3 cells reveal that when the concentration of the drug was beyond 100µg/mL, the cell viability of BUC@ZMS and UC@ZMS was found to be ~65% and ~79% respectively.

One of the research focuses on visualization and multi-modeling imaging, magnetic resonance imaging, fluorescence imaging, and photoacoustic imaging altogether for the disease progression. A549 lung cancer cells were coated with nanoparticles to promote their diagnostic efficiency.131 PP@ICGNPs having a cancer cell membrane coating allow them to potentially accumulate at tumor-specific sites. Inhibition of tumor development was attained after AM-PP@ICGNPs administration in a mouse model during in vivo studies. Gastric cancer is considered the prevalent cancer across the world, where Platinum has been selected as the first-line chemotherapy drug for GC patients.126,132 So, the Manganese-coated mesoporous silica nanoparticle shows time-dependent biodegradable behavior. CCM@Mn@MSN-Pt(IV) shows homologous targeting abilities with suitable size distribution and enhanced biocompatibility, and so has in vitro a more substantial impact on the immune regulation.132 Biosafety was checked for the CMnMPt by measuring the cytotoxicity in normal cells, and it was found that when applied to cancer cells, CMnMPt NPs showed selective cytotoxicity, whereas normal cells were only mildly affected.

Figure 4 (A) Schematic illustration of the construction and evaluation of biomimetic SU-OE@Dox NPs. Reproduced with permission from Zhang J, Yang Q, Zhang Y et al. Cancer cell membrane-coated sulindac-ortho ester nanoprodrug for inhibiting COX-2 expression and chemo-photothermal synergistic antitumor therapy. Int J Pharm.133 Copyright 2025, Elsevier. (B) Graphical representation of tumor profiles of different groups of mice from the antitumor study (*** for p<0.001). Reproduced with permission from Zhang J, Yang Q, Zhang Y et al. Cancer cell membrane-coated sulindac-ortho ester nanoprodrug for inhibiting COX-2 expression and chemo-photothermal synergistic antitumor therapy. Int J Pharm.133 Copyright 2025, Elsevier. (C) (i) SEM image showing stacked block-like structures of MXene (scale bar: 300 nm). (ii) TEM imaging of MXene blocks (scale bar: 100 nm). (iii) TEM imaging of dispersed MXene sheets (scale bar: 100 nm). Reproduced with permission from Yao Y, Zhang J, Huang K et al. Engineered CAF-cancer cell hybrid membrane biomimetic dual-targeted integrated platform for multi-dimensional treatment of ovarian cancer. J Nanobiotechnology.134 Copyright 2025, The Authors. Creative Commons Attribution Non-Commercial License 4.0 (CC BY-NC). (D) Biodistribution of M-G-P/P and M-G-P/P@CM in lung tumor-bearing mice at various time intervals. Reproduced with permission from Yang K, Zhang C, Wang Z et al. CRISPR-dCas9-Mediated PTEN Activation via Tumor Cell Membrane-Coated Nanoplatform Enhances Sensitivity to Tyrosine Kinase Inhibitors in Nonsmall Cell Lung Cancer. ACS Appl Mater Interfaces.135 Copyright 2025, American Chemical Society.

Sulindac dimer linked via an ortho-ester bond and co-assembled with DOX forms a pH-sensitive nanodrug. These SU-OE@DOX NPs camouflages with the tumor cell membrane for inhibiting COX-2 expression and chemo-photo thermal synergistic anticancer therapy.133 The prepared biomimetic nanoparticle enhances H22 cellular uptake via homologous targeting and effectively alleviates macrophage internalization. The Biomimetic nanodrugs use sulindac-ortho ester small molecule prodrugs for cancer cell membrane targeting: A synergistic chemo-phototherapy approach analyzed in both in vitro and in vivo (Figure 4A). Combining NIR-range irradiation, the nanoparticles also induce heat, enabling photothermal therapy. The cell viability of SU-OE@DOX NPs incubated with H22 cells dropped from 83% to 20%. In contrast, the H22 cell survival after exposure to free DOX H22 cells dropped decreased from 88% at 16 μg/mL to 32% at 0.5 μg/mL, which indicates significant dose-dependent cytotoxicity. Apart from this, antitumor activity was performed in a mouse model via the intravenous route, demonstrating that HM@I/NPs treated with NIR laser exhibit the highest remarkable antitumor activity, as shown in the graph (Figure 4B). The dual approach of chemotherapy and photothermal therapy worked synergistically to significantly inhibit tumor growth in animal models, with minimal side effects, underscoring the potential of this strategy for effective and targeted cancer treatment.133

Another approach of research in biomimetic nanoparticles for cancer treatment includes cancer-associated factor (CAF) and cancer cell membrane (CCM) hybrid membrane biomimetic nanoparticles loaded with carboplatin (CBP) and siRNA (PH20/CCM@PMCS), a cancer-associated combined targeted multidimensional treatment for ovarian cancer. In SEM and TEM images, MXene appears as stacked layers, whereas after extended sonication, the TEM images display a well-dispersed morphology of MXene sheets (Figure 4C). Furthermore, the entrapment efficiency of CBP and siRNA was 82.98% and 71.79%, and the drug loading capacity was 71.34% and 1.75%, respectively. The DLS analysis detected that after loading the CBP, the surface charge of PH20/CCM@PMCS was −13.3 ± 4.3 mV, and this negatively charged nanoparticle enhances the blood circulation time of NPs.134

A tumor cell membrane-coated nanoplatform to deliver CRISPR-dCas9 for targeted activation of the PTEN tumor suppressor gene in non-small cell lung cancer (NSCLC) was analyzed by research scientists to combat cancer. Reactivation of PTEN expression enhances the sensitivity of cancer cells to tyrosine kinase inhibitors (TKIs), which helps to eradicate drug resistance.135 However, both in vitro and in vivo experiments demonstrated significant tumor growth inhibition, improved apoptosis, and increased therapeutic efficacy when combined with TKIs. This approach offers a promising gene-based strategy to boost the effectiveness of targeted therapies in NSCLC. Indocyanine (ICN) dye was used to mark the drug carrier to visualize the drug distribution within the animals. It was found that M-G-P/P and M-G-P/P@CM were distributed in the tumor sites, liver, and lung, and their fluorescence intensity remained strong for 48 hours (Figure 4D). Additionally, long-term safety, immune response, and scalability of the tumor cell membrane-coated nanoplatform remain to be fully evaluated before clinical translation. The limitation of the study is the potential off-target effects and delivery efficiency challenges associated with the CRISPR-dCas9 system in complex in vivo environments.135

Exosome Membrane-Coated NPs

Exosome membrane-coated nanoparticles, or Exo-NPs, have emerged as a groundbreaking approach in cancer treatment by leveraging exosomes’ natural ability to transport drugs precisely and selectively. This novel strategy leverages the inherent qualities of exosomes to address challenges associated with traditional cancer therapy methods.136 One of the key benefits of Exo-NPs in tumor therapy lies in their ability to achieve targeted drug delivery. The surface proteins on exosome membranes can be tailored to interact with specific receptors overexpressed on cancer cells, enabling precise localization of therapeutic payloads and minimizing damage to healthy tissues.137 Exosome membrane-coated nanoparticles are uniquely positioned to navigate the complex biological barriers encountered in cancer treatment. Their biomimetic nature allows them to exploit endogenous cellular uptake mechanisms and facilitate efficient penetration through the TME, thus enhancing drug delivery to cancer cells. Exo-NPs offer a framework for customized cancer treatment by enabling the combination of specific targeting ligands and therapeutic agents tailored to the molecular profile of individual cancers.138 This precision medicine approach may reduce side effects while improving treatment outcomes.

Recently, researchers addressed limitations in ultrasound diagnosis and drug delivery by developing exosome-fused microbubbles.139 These exosome membrane-coated microbubbles exhibit enhanced stability and active targeting capabilities. And, under ultrasound exposure, they display favorable targeting properties to their original cells. Also, loading of the photosensitizer chlorin e6 into exosome-fused microbubbles resulted in improved therapeutic efficacy for enhanced photodynamic therapy and cancer immunotherapy. This innovative platform represents a novel ultrasound image-guided drug delivery system, thus overcoming conventional limitations and enabling dual-mode therapy. As discussed above, cancer treatment has undergone significant improvements and modernizations using biomimetic nanoparticles. Among them, exosome membrane-coated biomimetic nanoparticles have been a prominent approach in targeting cancerous cells.75 Its biocompatibility, stability, and ability to act a