An Activatable Phototheranostic Probe for Anti‐hypoxic Type I Photodynamic‐ and Immuno‐Therapy of Cancer

Author:

Zhao Min1,Zhang Yuyang1,Miao Jia1,Zhou Hui1,Jiang Yue1,Zhang Yuan1,Miao Minqian1,Chen Wan1,Xing Wei2,Li Qing1,Miao Qingqing13ORCID

Affiliation:

1. State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences (RAD‐X) Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Soochow University Suzhou 215123 China

2. Department of Imaging the Third Affiliated Hospital of Soochow University Changzhou Jiangsu 213003 China

3. School of Nuclear Science and Technology University of Science and Technology of China Hefei 230026 China

Abstract

AbstractPhotodynamic therapy (PDT), which utilizes type I photoreactions, has great potential as an effective cancer treatment because of its hypoxia‐tolerant superiority over the commonly used type II pathway. A few type I photosensitizers are exploited; however, they majorly induce cytotoxicity and possess poor tumor specificity and low‐efficient theranostics. To resolve this issue, herein an aminopeptidase N (APN)‐activated type I phototheranostic probe (CyA) is reported for anti‐hypoxic PDT in conjunction with immunotherapy for effective cancer treatment. CyA can specifically activate near‐infrared fluorescence, photoacoustic signals, and phototoxicity following APN‐induced substrate cleavage and the subsequent generation of active phototheranostic molecules (such as CyBr). CyA endows specific imaging capabilities and effective phototoxicity toward tumor cells overexpressing APN under both normoxia and hypoxia. In addition, the locally activatable PDT induces systemic antitumor immune responses. More importantly, the integration of localized activated PDT and systemic immunotherapy evokes enhanced therapeutic effects with improved tumor inhibition efficiency in live mice compared with individual treatments. This study aims to present an activatable phototheranostic probe for effective hypoxia‐tolerant PDT and combination therapy.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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