Synthesis of a light-responsive platinum curcumin complex, chemical and biological investigations and delivery to tumor cells by means of polymeric nanoparticles

Abstract

Platinum-based anticancer drugs are common in chemotherapy, but problems such as systemic toxicity and acquired resistance of some tumors hamper their clinical applications and therapeutic efficacy. It is necessary to synthesize Pt-based drugs and explore strategies to reduce side effects and improve pharmacokinetic profiles. Photo-responsive chemotherapeutics have emerged as an alternative strategy against several cancers, as photoactivation offers spatial selectivity and fewer side effects. Here, we combine chemical synthesis and nanotechnology to create a multifunctional platinum drug delivery system based on the novel metal complex [Pt(ppy)(curc)] (ppy = deprotonated 2-phenylpyridine, curc = deprotonated curcumin)] embodying the naturally occurring bioactive molecule, curcumin. The ultrasonication method coupled with the layer-by-layer technology was employed to produce nanocolloids, which demonstrated a good biocompatibility, higher solubility in aqueous solution, stability, large drug loading, and good biological activity in comparison with the free drug. In vitro release experiments revealed that the polymeric nanoformulation is relatively stable under physiological conditions (pH = 7.4 and 37 °C) but sensitive to acidic environments (pH = 5.6 and 37 °C) which would trigger the release of the loaded drug. Our approach modifies the bioavailability of this Pt-based drug increasing its therapeutic action in terms of both cytotoxic and anti-metastasis effects.