Red-light-triggered self-destructive mesoporous silica nanoparticles for cascade-amplifying chemo-photodynamic therapy favoring antitumor immune responses.

Abstract

Although chemo-photodynamic therapy demonstrates promising synergetic therapeutic effects in malignant tumors, the light-controlled drug release, synergism and biocompatibility of current nanocarriers are limited. Herein, we report a red light-responsive, self-destructive carrier constructed using polyethylene glycol-modified, diselenide-bridged mesoporous silica nanoparticles. The carrier is co-encapsulated with the chemo-drug doxorubicin and the photosensitizer methylene blue for chemo-photodynamic therapy. Upon low-dose red light irradiation during photodynamic therapy (PDT), the reactive oxygen species (ROS) mediates a diselenide bond cleavage resulting in the degradation of the organosilica matrix and a dual drug release. This, in turn, results in a synergistic chemo-photodynamic performance in vitro and in vivo. More importantly, such cascade chemo-PDT boosts immunogenic cell death and robust anti-tumor immunity responses. Combination with a PD-1 checkpoint blockade further evokes a series of systemic immunity responses that suppress distant tumor growth and the pulmonary metastasis of breast cancer, as well as offer long-term protection against recurrent tumors. The presented work offers a controllable self-destruction nanoplatform for cascade-amplifying chemo-photodynamic therapy in response to external red light radiation.

• Authors: Yanjun Yang, Fangman Chen, Ning Xu, Qichao Yao, Ran Wang, Xiaochun Xie, Fan Zhang, Yan He, Dan Shao, Wen-Fei Dong, Jiangli Fan, Wen Sun, Xiaojun Peng
• Journal: Biomaterials (Biomaterials) Vol. 281 Pg. 121368 (02 2022) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 35030436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Photosensitizing Agents
• Silicon Dioxide
• Doxorubicin

Topics

• Cell Line, Tumor
• Doxorubicin (chemistry, pharmacology, therapeutic use)
• Humans
• Immunity
• Nanoparticles (chemistry)
• Neoplasm Recurrence, Local
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry, therapeutic use)
• Silicon Dioxide (chemistry)