Micellar self-assembly from pH-responsive polymer prodrug for targeted antitumor drug transportation

Antineoplastic drug-conjugated pH-responsive polymeric nanoparticles have attracted much attention because of their efficacy in killing carcinoma cells with minimum side effects on normal cells. In the present work, we have synthesized an amphiphilic block copolymer Poly(PEGMA-<i>b</i>-DOPMA) to formulate a pH-responsive biocompatible polymeric prodrug system (PDBD) having antineoplastic drug doxorubicin (DOX) conjugated to the polymeric side chain through 4-formylphenylboronic acid. The self-assembly behavior, pH-responsive structural changes, drug loading content, and controlled <i>in-vitro</i> release of DOX from PDBD nanoparticles in both physiological and acidic conditions were studied using dynamic light scattering, fluorescence spectroscopy, UV-vis spectroscopy, and transmission electron microscopy. The synthesized prodrug nanoparticles were also evaluated for their <i>in vitro</i> toxicity, uptake efficiency, and pH-responsive activities against breast cancer cell lines. In MTT assay, the PDBD nanoparticles were found to have a significantly lower IC₅₀ value against MCF-7 cancer cells in comparison to free DOX. The cytotoxic effects of the nanoparticles on cancer cells were also evident from the morphological distortion of the MCF-7 cells revealed in phase contrast microscopy images. Efficient cellular uptake followed by pH-responsive drug release was also monitored in the MCF-7 cancer cells by fluorescence microscopy, indicating these prodrug nanoparticles to be potent nanocarrier systems for cancer therapy.