Multifaceted NIR-responsive polymer-peptide-enveloped drug-loaded copper sulfide nanoplatform for chemo-phototherapy against highly tumorigenic prostate cancer

Targeted, biocompatible, and synergistic “all in one” systems should be designed to combat the heterogeneity of cancer. In this study, we constructed a dual function nanosystem, copper sulfide nanoplatform loaded with the chemotherapeutic drug docetaxel wrapped by a conjugated polymer-peptide for targeted chemo-phototherapy. The nanoconstruct has been successfully designed with a size of 186.1 ± 5.2 nm, a polydispersity index of 0.18 ± 0.01, and zeta potential of −16.4 ± 0.1 mV. The enhanced uptake and near-infrared-responsive behavior of the nanosystem resulted in efficient drug release, photothermal ablation, effective cytotoxic activity, and potentiated reactive oxygen species generation. The induction of apoptotic markers, enhanced accumulation in the tumor site, and maximum tumor growth inhibition were seen during in vivo studies compared to non-targeted nanoformulations and free drug. Cumulatively, our results indicate that, with low systemic toxicity and better biocompatibility, this nanoconstruct could provide a promising strategy for treating prostate cancer. Docetaxel-loaded copper sulfide nanoconstruct functionalized by conjugated polymer-peptide (CuS-DTX-DSPE-PEG-LAN) was successfully designed for tumor-targeted chemophototherapy. CuS-DTX-DSPE-PEG-LAN as nanocarrier and photothermal agent, enables better loading capacity and NIR responsive release of docetaxel for ablation of cancer cells. With somatostatin receptors (SSTRs), CuS-DTX-DSPE-PEG-LAN was effectively endocytosed through active targeting mechanism for NIR driven targeted photothermal, photodynamic and chemotherapy. In a nutshell, CuS-DTX-DSPE-PEG-LAN may stand out as a hopeful candidate in the field of nanomedicine with its better accumulation, tumor ablative behavior, low systemic toxicity, and better biocompatibility. [Display omitted]