Mesoporous silica-based nanodevice for targeted cancer therapy

Cancer remains the major global health issue which continues to impact life expectancy. Many treatment approaches have been developed to address this disease, including surgery, radiotherapy, and chemotherapy [1,2]. Among these, conventional chemotherapy is considered the most effective treatment option for various types of cancer. However, the efficacy of most anticancer agents is hampered by several challenges, including short half-life, low bioavailability, multidrug resistance, non-specific- distribution, and difficulty in crossing physiological barriers. As a result, patients often experience more adverse effects than benefits. Doxorubicin (DOXO) is a potent anthracycline anticancer drug with a broad spectrum of antineoplastic activity. It is widely used in the treatment of many human cancers, such as breast, ovarian, thyroid, multiple myeloma, and sarcoma [3]. Nevertheless, the use of DOXO in cancer chemotherapy presents serious drawbacks, especially cardiotoxicity, myelosuppression, nephrotoxicity, and the risk of extravasation, which limit its clinical application [4]. In recent years, the rapid advancement of nanotechnology has introduced new ideas and approaches for cancer treatment, particularly in the exploration of novel drug delivery systems. The delivery of anticancer drugs through a nanocarrier is a successful strategy to improve efficacy and safety in cancer therapy. Drug delivery systems (DDSs) offer the benefits of site-specific drug targeting, controlled release, lower dose administration, and reduced side effects. As a result, numerous nanomaterials have gained considerable attention as promising DDSs. Among these, mesoporous silica nanoparticles (MSNs) have emerged as versatile and advanced nanosystems, owing to their advantageous features, including high surface area, large pore volume, tuneable particle size, easy surface functionalization, ability to carry different drugs, good biocompatibility, and low toxicity [5]. Internal surface modifications with responsive functional groups ensure the release of drug under specific physiological conditions, while targeting molecules on the external surface guide MSNs to deliver the drug selectively to the desired tissue [6]. In this study, we present a mesoporous silica-based nanodevice (MSN), named FOL-MSN-DOXO, which incorporates the antineoplastic drug DOXO linked to the MSN pores via a hydrazone bond, and exhibits folic acid (FOL) as a targeting function on the MSN external surface. The nanodevice is designed to release DOXO in response to the acidic tumor microenvironment. In vitro experiments were conducted to assess the efficacy of FOL-MSN-DOXO against folate receptor overexpressing (FR+) cancer cells (HeLa and T47D cells), as well as normal FR-low cells (3T3L1 normal fibroblasts). FOL-MSN-DOXO selectively killed FR+ cancer cells while sparing the FR-low normal cells, whereas free DOXO showed toxicity towards all tested cell lines. Notably, the nanocarrier alone, without the inclusion of the drug, FOL-MSN, exhibited no signs of toxicity, clearly indicating the remarkable biocompatibility and safety of the vehicle itself. These promising findings highlight the potential of MSN-based technology, making it a valuable and significant contribution to targeted cancer treatment.