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.

粘膜给药和跨粘膜聚合物载体在局部治疗中表现出特殊的优势，然而，其跨粘膜递送效率不令人满意且疏水性或生物大分子药物负载有限。在此，我们展示了几种苯硼酸修饰的壳聚糖衍生物来筛选出自组装纳米系统。壳聚糖骨架 (CS) 中合成的苯硼酸单元与吡柔比星 (THP) 和 aPD-1 的氨基提供供体-受体配位[1] , [2] , [3],载药量由CS的18.2±0.4%提高到37.0±1.0%。此外，苯硼酸修饰通过与粘膜糖胺聚糖的非共价结合为阳离子 CS 提供了额外的跨粘膜优势，并增强了药物通过内吞作用、高尔基体内质网和胞吐作用途径的渗透能力。此外，封装的药物可以选择性地释放以响应肿瘤组织中的高活性氧浓度，这与增强的跨粘膜能力相结合，极大地有助于提高 BCS@THP 和 BCS@aPD-1 NPs 在膀胱中的治疗效果和生物安全性癌症灌注治疗以及肺癌吸入治疗。更令人兴奋的是，除了THP和aPD-1，