Photodynamic therapy (
PDT) is an exceedingly promising
cancer treatment. However, the hypoxic environment in
tumor and the low penetration efficiency of short-wavelength light limit the effects of
PDT. In this paper, an
injectable red blood cell membrane doped
hydrogel system (UCNPs/S7942/RB-RHY) containing upconversion nanoparticles (UCNPs), a
photosensitizer (
Rose Bengal) and a strain of cyanobacteria Synechococcus elongatus PCC 7942 (S. 7942) was developed to improve the
PDT effects with a good biocompatibility and biosafety. In the system, S. 7942 was capable of inexhaustibly generating
oxygen triggered by the 640 nm
laser irradiation for alleviating hypoxic tumor microenvironment. In addition, UCNPs converted near-infrared light to visible light upon excitation by a 980 nm
laser, which further activated the
photosensitizer to release reactive
singlet oxygen to eradicate
tumors. In vivo experiments showed that the
tumor volume in the UCNPs/S7942/RB-RHY combined 640 nm with 980 nm light group was 496.9 mm3, in compared with 955.5 mm3 of the
tumor volume in the group without irradiation. The results demonstrated that UCNPs/S7942/RB-RHY was able to not only dramatically alleviate tumor hypoxia but also achieve a more efficient
PDT treatment. The
oxygen-generating system described here provides a new idea for
hypoxia-resistant
cancer therapy in the future.