Abstract
Cancer 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.
Highlights
Cancer cells in hypoxic tumors are remarkably resistant to photodynamic therapy
Oxygen would be significantly consumed during the photodynamic therapy (PDT) process to generate reactive oxygen species (ROS), the existence of hypoxia usually leads to low efficacy of PDT treatment[8]
The content of Pt measured by Elan DRC II inductively coupled plasma mass (ICPMS) and that of chlorin e6 (Ce6) measured by UV-vis absorption spectroscopy are 6.5 wt% and 20.1 wt% respectively, which confirms the molar ratio of Pt(IV) and Ce6 is 1:1 (Supplementary Fig. 9 and Supplementary Discussion 2). 1H nuclear magnetic resonance (1H NMR), Fourier transform infrared (FTIR), UV-vis, and X-ray photoelectron spectroscopy (XPS) spectra further certified the successful synthesis of CPP prodrug and its control samples (Supplementary Figs 1–8 and Supplementary Discussion 1)
Summary
Cancer 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. When a 980 nm laser irradiation is applied to trigger UCPP decomposition, O2 can be generated to compensate the consuming of oxygen during the PDT process and active Pt(II) can be released for a synergistic photo-chemo therapy (Fig. 1a). In this approach, co-delivery of O2-evolving materials, such as MnO2 or catalase etc., is not necessary and the restriction of hypoxia during the PDT treatment can be addressed. Associated with photo-generated Pt(II) species, anticancer efficacy can be dramatically enhanced by the synergistic PDTchemotherapy
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