A Tumor Environment‐Activated Photosensitized Biomimetic Nanoplatform for Precise Photodynamic Immunotherapy of Colon Cancer

Author:

Xiong Mengmeng1,Zhang Ying2,Zhang Huan1,Shao Qiaoqiao3,Hu Qifan4,Ma Junjie1,Wan Yiqun1,Guo Lan1,Wan Xin1,Sun Haitao3,Yuan Zhongyi1,Wan Hao2ORCID

Affiliation:

1. School of Chemistry and Chemical Engineering Nanchang University Nanchang 330031 P. R. China

2. State Key Laboratory of Food Science and Resources Nanchang University Nanchang 330047 P. R. China

3. State Key Laboratory of Precision Spectroscopy School of Physics and Electronic Science East China Normal University Shanghai 200241 P. R. China

4. Postdoctoral Innovation Practice Base The First Affiliated Hospital Jiangxi Medical College Nanchang University Nanchang 330006 P. R. China

Abstract

AbstractAggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment‐activated photosensitized biomimetic nanoplatform (PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM) is fabricated by encapsulating metal‐organic framework loaded with developed photosensitizer PEG2000‐SiNcTI‐Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD‐1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5′‐triphosphate (ATP))‐activated photodynamic effect sensitized by long‐wavelength photons is validated for PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM, advancing the precision of cancer therapy. Moreover, PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD‐1/programmed death ligand 1 (PD‐L1) interaction, respectively. Tumor environment‐activated photodynamic therapy realized by PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM induces immunogenic cell death (ICD) to elicit anti‐tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD‐L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Jiangxi Province

Shanghai Rising-Star Program

Publisher

Wiley

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