Glucose-Responsive Disassembly of Polymersomes of Sequence-Specific Boroxole-Containing Block Copolymers under Physiologically Relevant Conditions

Abstract

Polymers containing organoboronic acids have recently gained interest as sugar-responsive materials owing to the reversible binding of saccharides to boronic acids, which triggers a change in the physical and chemical properties of these polymers, such as their water solubility. In particular, the ability of these polymers to bind glucose has attracted considerable attention because of the promise of these materials for the development of sensors and drug delivery systems for glucose-related human diseases, such as diabetes. We report here a new class of sugar-responsive polymers that are based on a sequence-specific copolymer of styreneboroxole and N-functionalized maleimide. The reversible addition−fragmentation and chain transfer (RAFT) polymerization of this pair of monomers ensured that a glucose receptor alternates with a nonresponsive solubilizing group throughout the sugar-responsive polymer chain. Due to the presence of hydrophilic solubilizing groups beween the solubility-switching boroxole moieties in the membrane-forming block, the polymersomes of the block copolymers responded to a lower level of glucose in the medium, resulting in diassembly of the bilayer membrane under a physiologically relevant pH and glucose level.

Polypeptide-participating complex nanoparticles with improved salt-tolerance as excellent candidates for intelligent insulin delivery

“…[3][4][5] Amongst these self-regulated insulin delivery systems, synthetic phenylboronic acid (PBA)-based polymeric materials with high stability have shown more promising applications than glucose oxidase (GOD) and lectin (Con A) based systems. [6][7][8] Until now, a variety of PBA-based glucose-responsive materials particularly in the form of nanoparticles including nanogels (microgels), [9][10][11] micelles, [12][13][14][15] vesicles, [16][17][18][19][20] and mesoporous silica nanoparticles 21,22 have been broadly explored and shown to exhibit effective glucose-responsiveness at physiological pH and reasonable glucose-sensitivity.…”

Responsive Boronic Acid-Decorated (Co)polymers: From Glucose Sensors to Autonomous Drug Delivery

“…By performing an alternating copolymerization of styreneboroxoles with N -functionalized maleimides, various PEG containing block copolymers were synthesized that formed uniform polymersomes in both neutral buffer and serum (Figure 5). Due to the nature of the polymersomes, water-soluble drugs can be contained and shielded within the aqueous environment of the self-assembled core without the need for chemical modification [47]. …”

Recent Advances in the Synthesis and Applications of Organoborane Polymers

“…Moreover, the functional group tolerance is generally higher as the need for reactive borane species such as BBr 3 or transition metal catalysts can be circumvented. This allows for a greater variety of other functional comonomers to be incorporated, including acrylates, acrylamides, vinylpyridines, and ethylene oxide [39][40][41][42][43][44]. However, the polymerizability of each new monomer has to be investigated and the polymerization conditions carefully optimized.…”

“…In a different approach, Kiser and coworkers incorporated more acidic boroxoles [139,140] into polymer structures [141][142][143][144]. Related block copolymers (55,56) were investigated by Kim and coworkers as building blocks of responsive vesicles for insulin release applications [36,40]. Narain and coworkers found that the combination of boroxolefunctionalized polyacrylamide copolymer 57 with glycopolymers resulted in temperature-, pH-, and glucose-responsive gels [39].…”