Multifunctional Nanoparticles Fabricated by Dispersion Polymerization for the Treatment of Triple-Negative Breast...

This work presented the design and development of pH-sensitive nanoparticles fabricated by dispersion polymerization (PEG-surface-tagged polymeric nanoparticles) loaded with cisplatin and paclitaxel. In vitro drug release and in vitro drug efficacy of the dual-loaded nanoparticles were carried out vis-à-vis their suitability for the treatment of triple-negative breast cancer (TNBC). A pH-sensitive acetal crosslinking agent was synthesized followed by incorporation in polylactide, poly(ε-caprolactone and polylactide-poly(ε-caprolactone) (blend) nanoparticles to facilitate the hydrolysis of the nanoparticle matrix in the tumor acidic microenvironment and the release of the encapsulated drugs. The efficacy of paclitaxel and cisplatin, when combined, and the nature of their interaction were determined based on a combination index in an in vitro cell-based assay (antiproliferative studies) using a triple-negative breast cancer cell line (MDA-MB-231). Data show a synergistic interaction between paclitaxel and cisplatin: the two drugs work together to enhance efficacy. Combination Index values for the different formulations were less than 1, showing synergism. The drug combination demonstrated greater cytotoxicity at lower doses compared to higher doses of paclitaxel or cisplatin alone, indicating that this dual-loaded drug approach could maintain therapeutic efficacy while reducing adverse side effects commonly associated with chemotherapy at high doses. This novel strategy not only facilitates dose reduction of chemotherapeutic agents but also enables the simultaneous, site-specific delivery of both drugs, offering a promising advancement in targeted TNBC therapy. Confocal microscopy studies showed the internalization of the nanoparticles in the cytoplasm.