Enzyme‐Triggered Disassembly of Perylene Monoimide‐based Nanoclusters for Activatable and Deep Photodynamic Therapy

• Published in: Angewandte Chemie International Edition Vol. 59; no. 33; pp. 14014 - 14018
• Main Authors: Cai, Yang, Ni, Dongqi, Cheng, Wenyu, Ji, Chendong, Wang, Yaling, Müllen, Klaus, Su, Zhiqiang, Liu, Ying, Chen, Chunying, Yin, Meizhen
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 10.08.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: activatable photodynamic therapy; Albumins; Animals; Cancer; Carboxylesterase; Carboxylic Ester Hydrolases - metabolism; Cell Line, Tumor; Chemistry; Chemistry, Multidisciplinary; deep tumor penetration; Dismantling; enzyme-triggered disassembly; Enzymes; Fluorescence; Folic acid; Humans; Imides - chemistry; Infrared imaging; Mice; Nanoclusters; Nanoparticles; Nanostructures; NIR fluorescence imaging; Penetration; Perylene - chemistry; perylene monoimide; Photochemotherapy - methods; Photodynamic therapy; Photosensitivity; Photosensitizing Agents - pharmacology; Physical Sciences; Precision medicine; Science & Technology; Side effects; Singlet oxygen; Tumors; NANOPARTICLES; activatable photodynamic therapy; perylene monoimide; SIZE; deep tumor penetration; enzyme-triggered disassembly; NIR fluorescence imaging; CANCER
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202001107

Photodynamic therapy (PDT) exhibits great potential for cancer therapy, but still suffers from nonspecific photosensitivity and poor penetration of photosensitizer. Herein, a smart perylene monoimide‐based nanocluster capable of enzyme‐triggered disassembly is reported as an activatable and deeply penetrable photosensitizer. A novel carboxylesterase (CE)‐responsive tetrachloroperylene monoimide (P1) was synthesized and assembled with folate‐decorated albumins into a nanocluster (FHP) with a diameter of circa 100 nm. Once P1 is hydrolyzed by the tumor‐specific CE, FHP disassembles into ultrasmall nanoparticles (ca. 10 nm), facilitating the deep tumor penetration of FHP. Furthermore, such enzyme‐triggered disassembly of FHP leads to enhanced fluorescence intensity (ca. 8‐fold) and elevated singlet oxygen generation ability (ca. 4‐fold), enabling in situ near‐infrared fluorescence imaging and promoted PDT. FHP permits remarkable tumor inhibition in vivo with minimal side effects through imaging‐guided, activatable, and deep PDT. This work confirms that this cascaded multifunctional control through enzyme‐triggered molecular disassembly is an effective strategy for precise cancer theranostics. Things fall apart: A smart perylene monoimide‐based nanocluster (FHP) capable of enzyme‐triggered disassembly is reported as an activatable nano‐photosensitizer. FHP disassembles into circa 10‐nm nanoparticles, simultaneously leading to deep tumor penetration, enhanced fluorescence intensity (ca. 8‐fold), and elevated singlet oxygen generation (ca. 4‐fold).