Phenylboronic Acid-Functionalized Chitosan for Enabling Transmucosal Delivery for Cancer Therapy
Phenylboronic Acid-Functionalized Chitosan for Enabling Transmucosal Delivery for Cancer Therapy
复制标题
DOI：
10.1016/j.matdes.2023.111843
复制
发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Wenqi Jiang;Mingkang Liang;Qifang Lei;Dashi Deng;Chenchen Li;Yuqing Li;Simin Yuan;Kai Wu;Guangzhi Li;Song Wu
中科院分区：
文献类型：
--
作者：
Wenqi Jiang;Mingkang Liang;Qifang Lei;Dashi Deng;Chenchen Li;Yuqing Li;Simin Yuan;Kai Wu;Guangzhi Li;Song Wu
粘膜给药和经粘膜聚合物载体在局部治疗中表现出特定的优势，然而，局部治疗存在不令人满意的经粘膜递送效率和有限的疏水性或生物大分子药物负载。在此，我们展示了几种苯基硼酸修饰的壳聚糖衍生物，以筛选出一个自组装纳米系统。在壳聚糖骨架上合成的苯硼酸单元（CS）与吡拉西坦（THP）和aPD-1的胺基形成给体-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提供了额外的透粘膜优势，并增强了药物通过内吞、高尔基体-内质网和胞吐途径的渗透能力。此外，包封的药剂可以响应于肿瘤组织中的高活性氧浓度而选择性地释放，这与增强的透粘膜能力相结合，极大地有助于改善BCS@THP和BCS@aPD-1 NP在膀胱癌灌注治疗以及肺癌吸入治疗中的治疗功效和生物安全性。更令人兴奋的是，除了THP和aPD-1之外，我们的平台可以很容易地扩展到其他化疗药物和具有供电子基团的生物大分子药物，从而提供一种简单而强大的策略，以实现高效的基于粘膜给药的癌症治疗。
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.