Influence of poly(styrene-co-maleic anhydride) molecular weight on nanoparticle-mediated drug delivery in breast cancer

BACKGROUND: Paclitaxel (PTX) is a first-line chemotherapeutic agent widely used in the treatment of multiple malignancies; however, its clinical utility is limited by poor aqueous solubility, low bioavailability, lack of tumor specificity, and systemic toxicity. Nanocarrier-based targeted delivery systems offer a promising strategy to overcome these limitations. In this study, we systematically investigated the influence of polymer molecular weight on nanoparticle performance using poly(styrene-alt-maleic anhydride) (PSMA) as a model amphiphilic polymer for breast cancer therapy. METHODS: -PTX NPs) polymers and evaluated for physicochemical properties, drug loading efficiency, stability, cellular uptake, cytotoxicity, biodistribution, and antitumor efficacy in vitro and in Ehrlich Ascites Tumor (EAT) tumor-bearing syngeneic BALB/c mice. RESULTS: -PTX NPs) and free PTX. CONCLUSIONS: Polymer molecular weight critically governs nanoparticle stability, biodistribution, and therapeutic efficacy. Folate-targeted high-molecular-weight PSMA nanoparticles significantly enhance PTX delivery and antitumor activity, highlighting molecular weight as a key design parameter in the rational development of targeted nanocarrier systems for breast cancer therapy.