Dual Acidic pH-Responsive Post-Crosslinked E-Spun Nanofibrous Scaffolds Exhibiting Enhanced Disassembly and Release for Localized Cancer Treatment.

The development of multifunctional electro-spun nanofibrous mats has been explored as an effective platform for implantable localized cancer treatment because they provide a supportive matrix to regenerate tissues and deliver encapsulated anticancer drugs to suppress the proliferation of cancer cells. However, conventionally designed nanofibrous scaffolds present several critical challenges, particularly delayed and uncontrolled release of drug molecules due to inefficient crosslinks. Herein, we report a robust approach with the synthesis of a new phenyl diboronic acid crosslinker bearing an acid-cleavable Schiff base linkage to develop dual acidic pH-responsive degradable e-spun nanofibrous mats. The dual smart mats crosslinked with both acid-labile imine and boronic ester linkages, being structurally stable in a physiological pH, rapidly degrade through their acid-catalyzed hydrolysis in an acidic environment, leading to the enhanced release of encapsulated anticancer drugs. Furthermore, doxorubicin-loaded mats have desired antitumoral activity and hemocompatibility, while empty ones are biocompatible. These results demonstrate the great potential of dual acidic pH-responsive degradable e-spun nanofibrous mats as implantable localized drug delivery scaffolds for cancer chemotherapy.