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- Title
Synthesis of fluorinated CaCO<sub>3</sub>-based oxygen-supplying nanophotosensitizers to potentiate photodynamic immunotherapy by reversing tumor hypoxia and immunosuppression.
- Authors
Zhang, Yunyun; Dong, Ziliang; Hao, Yu; Gong, Yimou; Wang, Chunjie; Yan, Yifan; Chen, Minming; Wu, Yumin; Li, Quguang; Liu, Zhuang; Feng, Liangzhu
- Abstract
Photodynamic therapy is a noninvasive type of phototherapy with a high capacity to boost specific antitumor immunity by causing immunogenic cell death. However, the photodynamic therapeutic potency toward solid tumors is dampened by tumor hypoxia that negatively impairs the generation of cytotoxic singlet oxygen and promotes the formation of tumor immunosuppression. Herein, fluorinated CaCO3 (CaF) nanoparticles are prepared with the addition of dopamine-conjugated perfluorosebacic acid and ferric chloride into a calcium chloride ethanol solution via an ammonium bicarbonate-mediated gas-diffusion process. After being coated with commercial lipids and hexadecylamin conjugated chlorin e6 (hCe6) via a templated self-assembly process, the yielded PEGylated nanophotosensitizer (hCe6@CaF-PEG) exhibits an effective loading efficiency to perfluoro-15-crown-5-ether (PFCE), a model perfluorocarbon molecule, and thus oxygen molecules. Upon intravenous administration, the obtained PFCE/hCe6@CaF-PEG can alleviate tumor hypoxia by working as an oxygen nanoshuttle. Together with local light emitting diode light exposure, photodynamic treatment with PFCE/hCe6@CaF-PEG can suppress the growth of primary CT26 tumors and unirradiated distant tumors, particularly when synergized with anti-PD-1 (aPD-1) immunotherapy to collectively reverse tumor immunosuppression. This work presents an effective strategy to potentiate photodynamic immunotherapy by concurrently reversing tumor hypoxia and immunosuppression.
- Subjects
CALCIUM carbonate; LIGHT emitting diodes; CALCIUM chloride; PHOTODYNAMIC therapy; HYPOXEMIA; REACTIVE oxygen species; POLYETHYLENE glycol
- Publication
Nano Research, 2023, Vol 16, Issue 7, p9815
- ISSN
1998-0124
- Publication type
Article
- DOI
10.1007/s12274-023-5698-7