Singlet oxygen-responsive micelles for enhanced photodynamic therapy

• Published in: Journal of controlled release Vol. 260; pp. 12 - 21
• Main Authors: Li, Xiaodan, Gao, Min, Xin, Keting, Zhang, Ling, Ding, Dan, Kong, Deling, Wang, Zheng, Shi, Yang, Kiessling, Fabian, Lammers, Twan, Cheng, Jianjun, Zhao, Yanjun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.08.2017
• Subjects: Animals; Cell Line, Tumor; chlorins; composite polymers; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug delivery; Drug Liberation; Female; half life; hydrophilicity; hydrophobicity; Imidazole; Imidazoles - administration & dosage; Imidazoles - pharmacokinetics; irradiation; Light; mice; Mice, Inbred BALB C; Micelles; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; particle size; Photochemotherapy; Photodynamic therapy; photosensitizing agents; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacokinetics; Porphyrins - administration & dosage; Porphyrins - chemistry; Porphyrins - pharmacokinetics; singlet oxygen; Singlet Oxygen - metabolism; Singlet oxygen-responsive; urea; zinc; Drug delivery; Photodynamic therapy; Micelles; Imidazole; Singlet oxygen-responsive
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2017.05.025

Photodynamic therapy (PDT) efficacy is limited by the very short half-life and limited diffusion radius of singlet oxygen (1O2). We report a 1O2-responsive micellar nanoplatform subject to considerable size-expansion upon light triggering to facilitate on-demand release of photosensitizers. Imidazole, a well-known 1O2 scavenger, was incorporated in the hydrophobic core of amphiphilic copolymer micelles, and was used to coordinate with biocompatible Zn2+ and encapsulate the photosensitizer chlorin e6 (Ce6). The micelles are highly sensitive to light irradiation: 1O2 triggering induced dramatic particle size expansion due to the conversion of imidazole to hydrophilic urea, resulting in instantaneous release of Ce6 and rapid intracellular distribution. This 1O2-responsive, size-expandable nanosystem delivered substantially more Ce6 to tumor sites as compared to free Ce6, and exhibited improved anti-tumor efficacy in vivo in 4T1 tumor-bearing mice. This work opens new avenues of particle expansion-induced PDT enhancement by controlled imidazole chemistry. [Display omitted]