An Endogenous H2S-Activated Nanoplatform for Triple Synergistic Therapy of Colorectal Cancer.

Overproduced hydrogen sulfide (H2S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H2S and convert into high Fenton-catalytic Prussian white (PW), which can generate in situ a high level of •OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both in vitro and in vivo to have high efficacy in CRC treatment, showing promising potential in translational medicine.

Hypoxia-Induced Photogenic Radicals by Eosin Y for Efficient Phototherapy of Hypoxic Tumors.

The current reported photosensitizers generally show a decreased reactive oxygen species (ROS) generation property under hypoxia conditions, which is the main reason for the clinical failure of photodynamic therapy (PDT) in treatment of solid tumors. Herein, for the first time, hypoxia-induced photogenic radicals by eosin Y (Eos) were reported for efficient phototherapy of hypoxic tumors. More importantly, Eos shows a higher ROS and radical production efficiency under hypoxia conditions than under normoxia conditions. The photogenic radicals were captured by electron paramagnetic resonance and further verified by ROS and radical probe. Introducing CoCl2 as a hypoxia inducer, the photoinduced therapy of the hypoxia cancer cell model and tumor-bearing mice indicated that bovine serum albumin-Eos in hypoxic tumor sites can produce even higher tumor toxicity, thereby crossing the clinical obstacles of hypoxic tumor therapy. This non-oxygen-dependent PDT may open up an avenue for fighting with hypoxia.