Nanomedicine refers to the application of nanotechnology to diagnose, treat, and prevent various diseases. Nanomedicine frequently demonstrates superior efficacy compared to conventional therapeutic, or diagnostic agents, attributable to their size (typically in 10–100 nm), extensive specific surface area, and versatility in surface functionalization (Zhang et al., 2020). By encapsulating or attaching cargo, nanocarriers can improve the pharmacokinetic profile, toxicity, and therapeutic or diagnostic efficiency of delivered agents (Nguyen-Trinh et al., 2022, Vong et al., 2012). According to the type and structure of the delivery platforms, nanomedicines can be categorized into nanocrystal, polymeric, lipid, and inorganic nanoparticles (NPs) (Fig. 1).

Since many nano-formulations are recognized as foreign objects, they may be quickly adsorbed by biological molecules, including plasma proteins, antibodies, or complement components, resulting in opsonization and expedited elimination via reticuloendothelial system and mononuclear phagocytic system (MPS). In addition, the non-targeted NPs may cause systemic distribution, resulting in impairing the accumulation of NPs in disease sites, reducing therapeutic efficiency, and causing adverse effects. Alternation on the surface is an essential method contributing NPs to overcome the vast variability of biological barriers and illness conditions. Coating agents of NPs can be mainly classified according to their functions, including improving circulation time, resulting in increasing the accumulation and penetration in pathogen areas via enhanced permeability and retention (EPR) effect (passive targeting) and site-specific accumulation (active targeting).

It is important to deliver therapeutic and diagnostic agents to disease sites. Recent advancements have produced stimuli-responsive NPs designed to target disease microenvironments, using both passive and active targeting methods while negotiating related biological hurdles. In addition to these approaches, the stratergies for controlled cargo release at the specific disease sites are quite important especially in the case of highly toxic anti-tumor drugs to prevent their adverse effects on healthy tissues. After accumulating diseased tissues either by passive or active targeting, these nanocarriers can undergo structural transitions for regulated drug release upon stimulation by either exogenous or endogenous stimuli. In this chapter, we will focus on some advanced strategies for improving circulation time and site-specific accumulation of drugs via surface modifications of NPs. Several approaches to design smart NPs that respond to internal and external stimuli for controlling the drug release also be reviewed. Futhermore, recently approved nanomedicines are also updated and discussed.