Lactate and glucose responsive boronic acid-substituted amphiphilic block copolymer nanoparticles of high aspect ratio

Abstract

The establishment of conditions for formation of higher order morphologies (e.g. rods and worms) is important, as such nanoparticles are more efficient than spheres in drug delivery. Glucose-binding of core–shell nanoparticles comprising of boronic acid (BA) moieties occurs under basic conditions at above the pKa of the BA (pH 8.7). The resulting increased solubility of the core-forming BA-containing block is utilised in the delivery of therapeutics to diabetics. In contrast, the binding of the key anaerobic metabolite lactate to the BA moiety of amphiphilic block copolymers is unreported, despite occurring at lower physiological neutral pH 7.4. Herein, for the first time, high aspect ratio nanoparticles are observed for (unprotected) BA-substituted amphiphilic block copolymers in water, achieved by incorporating a non-stimuli responsive hydrophobic (tert-butylacrylamide) block. Amphiphilic diblock (Mn = 24,100 and 27,700 gmol−1) and triblock copolymers (Mn = 21,500 and 25,200 gmol−1) with relatively narrow molecular weight distributions (ᴆ = 1.31–1.48) were prepared by reversible addition-fragmentation chain transfer (RAFT) solution polymerizations. Aggregates formed upon dialysis with lactate at pH 7.4 were generally similar to those formed upon self-assembly with glucose at pH 8.7. Spherical nanoparticles for poly(N,N-dimethylacrylamide, DMA)28-b-(3-(acrylamidophenyl)boronic acid, 3-BAPhA)84-TTC (trithiocarbonate) decreased in size from Dh = 259 nm to mostly 100–150 nm upon ionization of BA-moieties with lactate, base, and glucose. Poly(DMA)96-b-(3-BAPhA)62 gave ∼ 500 nm long worms and lamellae under basic conditions, which transitioned to irregular spheres and rods upon addition of glucose. Self-assembly for triblock copolymers with BA-binding gave worms and fused spherical micelle rod-like structures.