Self-assembled NIPAM–PEG–NIPAM polymeric nanomicelles for the delivery of zinc protoporphyrin: a potential stimuli-triggered cancer treatment approach

Zinc protoporphyrin (ZnPP), known as a heme-oxygenase inhibitor, acts as an anticancer agent mainly by increasing free radical levels in the target cells and inducing cell death. However, its efficacy is restricted due to its poor solubility and numerous adverse reactions. To address this issues, nanopolymeric micelles have shown promising potentials in improving drug delivery while minimizing side effects. Here, thermoresponsive polymeric micelles based on PNIPAM–PEG–PNIPAM tri-block copolymer were developed to deliver ZnPP to prostate cancer cells (PC3). Being thermosensitive confers more structural stability and less drug leakage to the nanocarriers. Following the polymer characterization, the mean critical micelle concentration (CMC) and lowest critical solution temperature (LCST) were determined as 22.32 µg mL −1 and 36.20 °C, respectively. The prepared drug-loaded micelles at 37 °C exhibited an average diameter of 148 nm with the entrapment efficiency of 98% and drug loading capacity of 35%, in average. According to the in vitro outcomes, the ZnPP release rate from the nanomicelles followed a temperature-dependent manner. The obtained IC50 through the MTT assay on the PC3 cells treated by ZnPP-loaded micelles was 36% less than that of free drugs ( P < 0.01), which indicated the improved toxicity of our prepared formulation. In comparison with the free drug, in the equal ZnPP concentration, the drug-loaded micelles exhibited significantly greater ability to induce apoptosis in PC3 cells. Moreover, the flow cytometry and confocal microscopy evaluations confirmed the cellular uptake of our prepared nanoparticles. In conclusion, the produced nanomicelles showed promising potentials to serve as an effective drug delivery system in future researches on cancer therapy. Graphical abstract