Gold(III) Porphyrin-Metal-Polyphenolic Nanocomplexes: Breaking Intracellular Redox Environment for Enhancing Mild-Temperature Photothermal Therapy.

Photothermal therapy (PTT) is a promising clinical antitumor strategy. However, local hyperthermia inevitably induces heat damage to adjacent normal tissues, while alternative mild-temperature therapy (MPTT, T < 45 °C) is also inefficient due to the overexpressed hyperthermia-induced heat shock proteins (HSPs) by cancer cells. Therefore, developing PTT strategies with minimizing damage to healthy tissues with improved cellular temperature sensitivity is extremely valuable for clinical application. Herein, we proposed the strategy of disrupting the intracellular redox environment via destroying the ROS-defending systems to promote MPTT. The gold(III) porphyrin-Fe 3+ -tannic acid nanocomplexes (AuTPP@TA-Fe NPs) were achieved via interfacial cohesion and supramolecular assembly of bioadhesive species, which could trigger the Fenton reaction to produce ·OH radicals and downregulation of reductive TrxR enzyme and mitochondrial chaperone protein Hsp60. The aggravation of oxides and the inactivation of Hsp60 provide favorable pathways for impeding the heat shock-induced self-repair mechanism of cancer cells, which strengthens AuTPP@TA-Fe NPs mediated MPTT.