Rational design of platinum(Ⅱ)complexes with orthogonally oriented triazolyl ligand with emission enhancement characteristics for cancer chemotherapy in vivo

The mitochondria are essential for tumorigenesis and have been regarded as important targets in cancer chemotherapy.Herein,the mitochondria-targeted platinum(Ⅱ)complexes have been prepared.The introduction of the triazole group with larger steric hindrance through post-click reaction converts the hybridization of carbon from sp to sp^(2),endowing the complexes with an orthogonally oriented ligand with restricted rotation and emission enhancement characteristics.Methylation of the triazolyl ligand has led to platinum(Ⅱ)complexes that can efficiently enter cancer cells and selectively accumulate in mitochondria,leading to significant enhancement in phosphorescence.In vivo anti-cancer investigations have demonstrated their distinct antitumor efficacy in substantial inhibition of tumor growth in breast cancer mice through dissipation of mitochondrial membrane potential,inducing apoptosis of tumor cell with negligibly systemic cytotoxicity.

Tumor microenvironment triggered local oxygen generation and photosensitizer release from manganese dioxide mineralized albumin-ICG nanocomplex to amplify photodynamic immunotherapy efficacy

Photodynamic therapy(PDT) has emerged as a potential clinical strategy for tumor therapy. It can generate reactive oxygen species(ROS) to cause the chemical damage of tumor cells and promote the immune killing effects of T cells on tumor cells in the presence of enough oxygen and PDT drugs. However, most solid tumors are in a state of oxygen deficiency, which seriously limit the efficacy of PDT in generation enough ROS. Besides, few safe PDT drugs with ideal pharmacokinetic behavior are available in the clinic,which severely limits the clinical transformation and application of PDT. Herein, we utilized manganese chloride to mineralize the hydrophilic indocyanine green/albumin polyplexes(ICG@BSA@MnO_(2)) by using bio-mineralized method to solve these problems of PDT. These ICG@BSA@MnO_(2)nanoparticles could circulate in the blood for a long period other than quickly removed from body after 30 min like free ICG.When accumulated at the tumor site, ICG was responsively released in the presence of hydrogen peroxide. Apart this, the tumor hypoxia microenvironment was also reversed owing to enhanced O_(2)generation by the reaction of MnO_(2)with hydrogen peroxide. Benefits from the rich accumulation of ICG and ameliorated tumor hypoxia in the tumor sites, the enhanced generation of ROS could successfully promote the distribution of CD3^(+) and CD8^(+)T cells inside the tumors, which then lead to the amplified efficacy of PDT in both CT26 and B16 F10 tumor models without causing any side effects.