Design, Synthesis, and Acid-Responsive Disassembly of Shell-Sheddable Block Copolymer Labeled with Benzaldehyde Acetal Junction.

Smart nanoassemblies degradable through the cleavage of acid-labile linkages have attracted significant attention because of their biological relevance found in tumor tissues. Despite their high potential to achieve controlled/enhanced drug release, a systematic understanding of structural factors that affect their pH sensitivity remains challenging, particulary in the consruction of effective acid-degradable shell-sheddable nanoassemblies. Herein, the authors report the synthesis and acid-responsive degradation through acid-catalyzed hydrolysis of three acetal and ketal diols and identify benzaldehyde acetal (BzAA) exhibiting optimal hydrolysis profiles in targeted pH ranges to be a suitable candidate for junction acid-labile linkage. The authors explore the synthesis and aqueous micellization of well-defined poly(ethylene glycol)-based block copolymer bearing BzAA linkage covalently attached to a polymethacrylate block for the formation of colloidally-stable nanoassemblies with BzAA groups at core/corona interfaces. Promisingly, the investigation on acid-catalyzed hydrolysis and disassembly shows that the formed nanoassemblies meet the criteria for acid-degradable shell-sheddable nanoassemblies: slow degradation at tumoral pH = 6.5 and rapid disassembly at endo/lysosomal pH = 5.0, while colloidal stability at physiological pH = 7.4. This work guides the design principle of acid-degradable shell-sheddable nanoassemblies bearing BzAA at interfaces, thus offering the promise to address the PEG dilemma and improve endocytosis in tumor-targeting drug delivery.

pH-Responsive Degradable Electro-Spun Nanofibers Crosslinked via Boronic Ester Chemistry for Smart Wound Dressings.

Recent advances in the treatment of chronic wounds have focused on the development of effective strategies for cutting-edge wound dressings based on nanostructured materials, particularly biocompatible poly(vinyl alcohol) (PVA)-based electro-spun (e-spun) nanofibers. However, PVA nanofibers need to be chemically crosslinked to ensure their dimensional stability in aqueous environment and their capability to encapsulate bioactive molecules. Herein, a robust approach for the fabrication of pH-degradable e-spun PVA nanofibers crosslinked with dynamic boronic ester (BE) linkages through a coupling reaction of PVA hydroxyl groups with the boronic acid groups of a phenyl diboronic acid crosslinker is reported. This comprehensive analysis reveals the importance of the mole ratio of boronic acid to hydroxyl group for the fabrication of well-defined BE-crosslinked fibrous mats with not only dimensional stability but also the ability to retain uniform fibrous form in aqueous solutions. These nanofibers degrade in both acidic and basic conditions that mimic wound environments, leading to controlled/enhanced release of encapsulated antimicrobial drug molecules. More importantly, drug-loaded BE-crosslinked fibers show excellent antimicrobial activities against both Gram-positive and Gram-negative bacteria, suggesting that this approach of exploring dynamic BE chemistry is amenable to the development of smart wound dressings with controlled/enhanced drug release.