Glucose-Triggered Micellization of Poly(ethylene glycol)-b-poly(N-isopropylacrylamide-co-2-(acrylamido)phenylboronic acid) Block Copolymer

Abstract

Many glucose-sensitive micelles self-assembled from phenylboronic acid (PBA)-functionalized block copolymers have been reported; however, the addition of glucose always triggers the disassembly of the micelles. Herein, we reported a glucose-sensitive micelle of poly­(ethylene glycol)-b-poly­(N-isopropylacrylamide-co-2-(acrylamido)­phenylboronic acid) (PEG-b-P­(NIPAM-2-AAPBA)) block copolymer that responds to glucose in a very different way. Using a macro-reversible addition–fragmentation chain transfer (RAFT) agent, the block copolymer was synthesized by RAFT copolymerization of NIPAM and 2-AAPBA. Because of the thermosensitivity of the P­(NIPAM-2-AAPBA) block, the copolymer self-assembles into micelles upon heating. More importantly, the addition of glucose triggers the micellization of the copolymer instead of disassembly of the micelles. The unique behavior of PEG-b-P­(NIPAM-2-AAPBA) originates from the unique glucose-responsive mechanism of the P­(NIPAM-2-AAPBA) block. For common PBA-functionalized polymers, reaction with glucose results in more ionized form of the PBA group, turns the polymer from hydrophobic to hydrophilic, and thus leads to the disassembly of the micelles. Very differently, for P­(NIPAM-2-AAPBA), adding glucose lowers its lower critical solution temperature (LCST), turns it from hydrophilic to hydrophobic, and therefore triggers the micellization of the block copolymer. Besides glucose, sugars such as fructose, mannose, and galactose can trigger the self-assembly of PEG-b-P­(NIPAM-2-AAPBA) too.

Novel glucose-responsive nanoparticles based on p-hydroxyphenethyl anisate and 3-acrylamidophenylboronic acid reduce blood glucose and ameliorate diabetic nephropathy

“…It is thus confirmed that p(AAPPA-b-HPA) nanoparticles exhibit a glucose response, and the results are consistent with the behaviour of boric acid-containing block copolymers studied by Wang et al. [ 37 ].…”

Nanoparticles capable of managing hypoglycemia and preventing myocardial ischemia‐reperfusion injury

“…Chen et al 35 synthesized an AAPBA‐based glucose‐responsive hydrogel, and found that the constructed gel had good glucose sensitivity. Wang et al 36 manufactured a glucose sensitive micelle of poly(ethylene glycol)‐b‐poly( N ‐isopropylacrylamide‐ co ‐2‐(acrylamido)phenylboronic acid) (PEG‐b‐P(NIPAM‐2‐AAPBA)) block copolymer. Nanogels have also been found to have excellent glucose sensitivity, which supports the use of NPs constructed with PBA 36 …”

“…Wang et al 36 manufactured a glucose sensitive micelle of poly(ethylene glycol)‐b‐poly( N ‐isopropylacrylamide‐ co ‐2‐(acrylamido)phenylboronic acid) (PEG‐b‐P(NIPAM‐2‐AAPBA)) block copolymer. Nanogels have also been found to have excellent glucose sensitivity, which supports the use of NPs constructed with PBA 36 …”

“…Nanogels have also been found to have excellent glucose sensitivity, which supports the use of NPs constructed with PBA. 36 The reusability of NPs means that after swelling in different systems, NPs can be placed in PBS to eliminate swelling and return to their original state, without affect their reuse. 37 In this study, p(AAPBA-co-PTE) NPs were placed in a 0 mg/ml glucose solution for 1 h. After the particle size was determined using dynamic light scattering (DLS), the particles were lyophilized and taken out, and then placed in 3 mg/ml glucose solution again.…”

Bioresponsive Functional Phenylboronic Acid-Based Delivery System as an Emerging Platform for Diabetic Therapy

“…Moreover, it is a common glucose-sensitive material because of its costefficiency and easy fabrication. [11][12][13][14] This review focuses on the development process, performance, resolve resolution, and application of the glucose-sensitive polymer drug carrier of PBA and its derivatives, and also presents the prospective development direction and application in the field.…”