Improved anticancer efficacy of cisplatin co-delivered with nisin-decorated solid lipid nanoparticles

The therapeutic efficacy of cisplatin is limited by systemic toxicity, acquired resistance, and poor cancer cell specificity. To address these limitations, we developed solid lipid nanocarriers for the co-delivery of nisin and cisplatin (Nis + Cis-SLNs). The developed SLNs exhibited monodisperse spherical morphology, high encapsulation efficiency and sustained release. The therapeutic potential of Nis + Cis-SLNs was evaluated against epithelial malignancies using human epidermoid carcinoma (A431) and breast adenocarcinoma (MCF-7) cells. The nanocarriers demonstrated enhanced cytotoxicity compared to free nisin and cisplatin by synergistically targeting proliferation, apoptosis, and reactive oxygen species generation. Nis + Cis-SLNs triggered an intrinsic apoptotic response by upregulation of caspase-3, Bax, and suppression of Bcl-2. Beyond direct cytotoxicity, conditioned media derived from Nis + Cis-SLNs treated tumor cells were associated with reduced M2 macrophage polarization, suggesting a possible role in immunomodulation of the tumor microenvironment. Collectively, these findings highlight the potential of Nis + Cis-SLNs as a promising co-delivery strategy to enhance cisplatin efficacy at reduced doses, potentially improving therapeutic outcomes.