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A Novel Nanobody–Photosensitizer Conjugate for Hypoxia Resistant Photoimmunotherapy
Author(s) -
Xiong Tao,
Peng Qiang,
Chen Yingchao,
Li Mingle,
Du Jianjun,
Fan Jiangli,
Jia Lingyun,
Peng Xiaojun
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202103629
Subject(s) - photosensitizer , photodynamic therapy , in vivo , conjugate , cancer research , phototoxicity , monoclonal antibody , tumor hypoxia , materials science , biophysics , antibody , chemistry , in vitro , medicine , biology , radiation therapy , immunology , biochemistry , photochemistry , mathematical analysis , microbiology and biotechnology , mathematics , organic chemistry
Abstract As a non‐invasive treatment modality, photodynamic therapy has been a potential therapeutic method for metastatic and non‐metastatic tumors. In order to further improve the tumor selectivity, phtotoimmunotherapy (PIT) has been developed recently, which includes antibodies as the active targeting ligands. However, traditional monoclonal antibody‐based PIT suffers from long half‐lives and extended phototoxic side‐effects in vivo. Herein, a type I mechanism‐based photoimmunoconjugate (PIC) is developed by incorporating anti‐EGFR nanobody as the targeting ligand, and benzophenothiazine as the photosensitizer (PS). The small size and robust structure of the nanobody ensures excellent targeting accuracy and efficient renal excretion. Meanwhile, the type I PS is able to circularly transfer oxygen to superoxide radical upon irradiation to overcome hypoxia microenvironment. The PIC showed satisfying phototherapeutic ability both in normoxia and hypoxia, and displayed high selectivity towards tumor in vivo. By combining nanobody and Type I PS, the work presents a novel type of PIC for the precise treatment of tumors with high specificity and potency.