Cancer continues to pose a major global health burden, with the World Health Organization (WHO) reporting approximately ten million fatalities in 2020 alone. This staggering figure underscores its status as the second most prevalent cause of mortality worldwide [1]. This alarming statistic highlights the pressing need for more effective and targeted cancer therapies. Among the emerging anticancer agents, β-Lapachone, a naturally occurring o-naphthoquinone derived from the lapacho tree (Handroanthus impetiginosus), has shown considerable promise against a range of cancers, including ovarian, colon, lung, prostate, melanoma, pancreatic, and breast cancers [2].

The anticancer activity of β-Lapachone is primarily mediated through its interaction with the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which is overexpressed in various tumour types [3,4]. This interaction triggers a futile redox cycle that generates reactive oxygen species (ROS), leading to extensive DNA damage and selective apoptosis in cancer cells [5]. Despite its potent anticancer properties, the clinical application of β-Lapachone has been hindered by significant side effects, including nausea, vomiting, and neuropathy, which are primarily due to its non-specific distribution and off-target toxicity [6,7]. To address these challenges, advanced drug delivery systems, such as nanoparticle-based carriers [8,9], liposomes [10], and polymeric micelles [11], are being explored. These platforms aim to improve the therapeutic index of β-Lapachone by enhancing its bioavailability, targeting specificity, and controlled release, thereby maximizing its anticancer efficacy while minimizing systemic toxicity and adverse effects [[12], [13], [14], [15], [16], [17]].

The limitations of conventional chemotherapy, particularly the non-selectivity of anticancer drugs and their associated toxicity to healthy tissues, have driven extensive research into advanced drug delivery systems. Traditional methods are often plagued by issues such as hepatotoxicity, immunogenicity, and poor bioavailability [[18], [19], [20], [21]]. In response, nanotechnology has emerged as a promising avenue for addressing these challenges. Nanoparticles, with their high surface area and ability to penetrate cellular barriers, offer a revolutionary approach to targeted drug delivery [[22], [23], [24], [25], [26]]. Since their discovery in 1985 by Kroto et al. [27], nanostructures have garnered significant attention for their potential as drug nanocarriers. Among these, boron nitride (BN) nanoclusters are particularly notable due to their exceptional physicochemical properties, including high chemical and thermal stability, wide bandgap, and non-toxicity, making them ideal candidates for medical applications. Specifically, B12N12 nanoclusters have been identified as promising nanocarriers for drug delivery [[28], [29], [30], [31]]. Numerous theoretical studies on the interactions between drug molecules and both pure and doped B12N12 clusters indicate that these clusters exhibit enhanced sensing capabilities for drug molecules. Therefore, B12N12 clusters can be proposed as effective nanocarriers, potentially advancing drug delivery applications [[32], [33], [34], [35]]. In a previous study, Zhang et al. [32] investigated the application of transition metal-decorated B12N12 nanoclusters as potential carriers for nitrosourea drug delivery systems using density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. Their results demonstrated that drug adsorption onto the nanoclusters led to a notable decrease in the HOMO-LUMO energy gap and chemical hardness, facilitating improved electron transfer between the drug and the nanocluster. In a related study, Chukwuemeka et al. [33] explored the adsorption of fluorouracil (5-FU) on the B12N12 nanoclusters decorated with Au, Os, and Pt, finding that Pt and Os-decorated systems showed the most favorable potential for 5-FU delivery. The adsorption of Pt onto the outer surface of B12N12 nanoclusters induces substantial changes in the system's electronic and optical properties, resulting in enhanced reactivity. This modification has been leveraged to improve the solubility and stability of curcumin, as demonstrated in studies involving Platinum-functionalized B12N12 nanoclusters [34]. These findings suggest that Pt-functionalized B12N12 nanoclusters hold promise for improving the delivery and efficacy of curcumin-based therapeutic applications.

Given the therapeutic potential of β-Lapachone and its efficacy in treating various cancers, several studies have explored its interactions with pure and doped nanoclusters, which are considered potential drug delivery vehicles. For example, Gholami et al. [36] conducted a theoretical study on the adsorption of β-Lapachone on metal-encapsulated B36N36 nanoclusters, finding that encapsulation enhanced adsorption performance and enabled drug release in acidic cancer cell environments. Similarly, Rahimi et al. [37] investigated the interaction of β-Lapachone with BC2N nanosheets, demonstrating that β-Lapachone adsorption is most stable when aligned parallel to the nanosheet surface, with potential for targeted drug delivery in cancerous tissues. Khodadadi et al. [38] also studied the adsorption of the β-lapachone on the graphene nanosheet doped with the transition metals, and their results indicate that doping with Pt and Au atoms improves their adsorption properties and at the same time suggests that these clusters may exhibit characteristics ideal for an efficient delivery vehicle.

In this work, we present a theoretical investigation on the stability and electronic properties of the B12N12 nanocluster decorated with metal atom such as Ru, Rh and Au by using density functional theory (DFT) calculations at the B3LYP/LanL2DZ/6-311G(d,p) level of theory. The impact of β-Lapachone adsorption on the electronic structure and sensing capabilities of these nanoclusters have also been evaluated. To gain a deeper understanding of the interaction mechanisms, we utilize Non-Covalent Interaction (NCI) analysis based on Reduced Density Gradient (RDG) and Quantum Theory of Atoms in Molecules (QTAIM) calculations. To gain a deeper understanding of the nature of the interaction between the different species constituting the systems studied, we utilize Non-Covalent Interaction (NCI) analysis based on Reduced Density Gradient (RDG) and Quantum Theory of Atoms in Molecules (QTAIM) calculations. These advanced computational approaches provide detailed insights on the nature and strength of the interactions between β-Lapachone and the metal sites of the nanocages, revealing the fundamental principles governing their bonding behavior and their potential for applications in drug delivery system.