Oxygen and Pt(II) self-generating conjugate for synergistic photo-chemo therapy of hypoxic tumor

• DOI: 10.1038/s41467-018-04318-1
• Publication Date: 2018-05-20T19:49:24Z
• Authors: Shuting Xu; Xinyuan Zhu; Chuan Zhang; Wei Huang; Yongfeng Zhou; Deyue Yan
• Keywords: Male; Porphyrins; Science; Mice, Nude; 02 engineering and technology; Article; Rats, Sprague-Dawley; Mice; Cell Line, Tumor; Neoplasms; Animals; Humans; Prodrugs; Hypoxia; Platinum; Photosensitizing Agents; Chlorophyllides; Q; Rats; 3. Good health; Oxygen; Photochemotherapy; Nanoparticles; Female; Reactive Oxygen Species; 0210 nano-technology

AbstractCancer cells in hypoxic tumors are remarkably resistant to photodynamic therapy. Here, we hypothesize that an oxygen and Pt(II) self-generating multifunctional nanocomposite could reverse the hypoxia-triggered PDT resistance. The nanocomposite contains Pt(IV) and chlorin e6, in which upconversion nanoparticles are loaded to convert 980 nm near-infrared light into 365 nm and 660 nm emissions. Upon accumulation at the tumor site, a 980 nm laser is used to trigger the nanocomposite to generate O2 for consumption in the PDT process and to produce cytotoxic reactive oxygen species. The composite also releases active Pt(II) for synergistic photo-chemo therapy to enhance antitumor efficiency. The oxygen and Pt(II) self-generating prodrug is shown to have high potential to inhibit tumors out of the range of UV light, to overcome the hypoxia-triggered PDT resistance and significantly improve anticancer efficacy by the synergistic PDT-chemotherapy.