Phenylboronic acid-functionalized chitosan for enabling transmucosal delivery for cancer therapy

Mucosa administration and transmucosal polymeric carriers demonstrate specific advantages in locoregional therapy, which, however, suffer from unsatisfactory transmucosal delivery efficiency and limited hydrophobic or bio-macromolecular drug loading. Herein, we demonstrate several phenylboronic acid-modified chitosan derivatives to screen out a self-assembly nano-system. The phenylboronic acid unit synthesized in chitosan skeleton (CS) afforded donor–acceptor coordination with amidogen of pirarubicin (THP) and aPD-1[1], [2], [3],the drug loading content was increased from 18.2 ± 0.4% to 37.0 ± 1.0% compared with CS. Besides, the phenylboronic acid modification provided an additional transmucosal advantage for cationic CS via non-covalent binding with mucosal glycosaminoglycans and enhanced the penetration ability of drugs through the endocytosis, Golgi-endoplasmic reticulum and exocytosis pathway. Furthermore, the encapsulated agents can be selectively released in response to the high reactive oxygen species concentration in tumor tissues, which combined with enhanced transmucosal capacity extremely contribute to improving the therapeutic efficacy and biosafety of BCS@THP and BCS@aPD-1 NPs in bladder cancer perfusion therapy as well as lung cancer inhalation treatment. Even more exciting is that in addition to THP and aPD-1, our platform could be easily extended to other chemotherapeutics and bio-macromolecular agents with electron-donating groups, rendering a simple and robust strategy for enabling highly efficient mucosal administration-based cancer therapy.