Self-Immolative Polymersomes for High-Efficiency Triggered Release and Programmed Enzymatic Reactions

• Published in: Journal of the American Chemical Society Vol. 136; no. 20; pp. 7492 - 7497
• Main Authors: Liu, Guhuan, Wang, Xiaorui, Hu, Jinming, Zhang, Guoying, Liu, Shiyong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.05.2014
• Subjects: Alkaline Phosphatase - antagonists & inhibitors; Alkaline Phosphatase - chemistry; Alkaline Phosphatase - metabolism; composite polymers; depolymerization; drugs; encapsulation; enzymatic reactions; Hydrogen-Ion Concentration; hydrophilicity; Hydrophobic and Hydrophilic Interactions; hydrophobicity; Light; Lipase - antagonists & inhibitors; Lipase - chemistry; Lipase - metabolism; Molecular Structure; oxygen; Particle Size; Polymerization; Polymers - chemistry; Polymers - metabolism; protons; Surface Properties; ultraviolet radiation
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/ja5030832

Stimuli-triggered disassembly of block copolymer vesicles or polymersomes has been conventionally achieved via solubility switching of the bilayer-forming block, requiring cooperative changes of most of the repeating units. Herein we report an alternative approach by incorporating hydrophobic blocks exhibiting stimuli-triggered head-to-tail cascade depolymerization features. Amphiphilic block copolymers bearing this motif self-assemble into self-immolative polymersomes (SIPsomes). By modular design of terminal capping moieties, visible light, UV light, and reductive milieu can be utilized to actuate SIPsomes disintegration into water-soluble small molecules and hydrophilic blocks. The design of SIPsomes allows for triggered drug co-release and controllable access toward protons, oxygen, and enzymatic substrates. We also demonstrate programmed (OR-, AND-, and XOR-type logic) enzymatic reactions by integrating SIPsome encapsulation and trigger/capping moiety-selective cascade depolymerization events.