pH-responsive dual-drug-loaded bovine serum albumin nanoparticles for targeted cancer therapy

We report a facile synthesis of stable, folic acid (FA)-functionalized bovine serum albumin nanoparticles (FA-BSA NPs) for targeted dual-drug delivery in cancer therapy. These nanoparticles are designed to encapsulate the chemotherapeutic drug doxorubicin (DOX) and the antiemetic agents dexamethasone (DEX) or ondansetron (OND), aiming to enhance anticancer efficacy while reducing chemotherapy-induced nausea and vomiting (CINV). The resulting folic acid-functionalized BSA NPs, loaded with various drug combinations (DOX, DOX-DEX, DOX-OND, and DEX-OND), are predominantly spherical with smooth surfaces, although transmission electron microscopy (TEM) analysis reveals some variability in size and shape. The nanoparticles demonstrate high stability in phosphate-buffered saline (PBS) and encapsulation efficiencies above 85%. In vitro studies reveal significant anticancer effects, including modulation of proapoptotic genes in human cancer cells and reduction of tumor spheroids. Mechanistic assays reveal enhanced cytotoxicity and confirm pH-triggered drug release. Biodistribution analysis in zebrafish larvae indicates pan-body distribution with notable accumulation in the retina, swim bladder, and tail, without observable stress responses. In vivo studies further show modulation of key genes associated with apoptosis and oxidative stress, including markers of cardiotoxicity and hepatotoxicity. These findings suggest that folic acid-functionalized BSA NPs loaded with dual drugs offer a promising approach for targeted cancer therapy with minimized side effects.