Mitochondria Targeted AuCu@Ce6-TPP nanoparticles Alleviating Cancer Hypoxia for Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) has advanced rapidly in the treatment of cancer due to its low resistance and reduced adverse effects. However, hypoxia is one of the most significant obstacles that limit the therapeutic effect and clinical transformation of this noninvasive treatment. Numerous studies have been conducted on alleviating hypoxia to improve antitumor effect, but comprehensive nanosystems that simultaneously overcome hypoxia and other severely limitation of PDT are seldom reported. Here we report a multifunctional nanosystem AuCu@Ce6-TPP (ACCT) that alleviates hypoxia and targets mitochondria to enhance PDT of cancer. Mercaptoethyl-triphenylphosphonium and mercapto chlorin e6 were conjugated to AuCu nanoparticles and thus Ce6 photosensitized 1O2 can cause direct damage to mitochondria, leading to mitochondrial apoptosis Copper can catalyze hydrogen peroxide degradation to alleviate hypoxia, whereas gold can consume glutathione to elevate the oxidative stress. ACCT-sensitized PDT leads to tumor growth inhibition rate of 92.8% on 4T1 tumor-bearing mice model. This work therefore demonstrates a potential solution to enhance PDT on hypoxic tumors.