Liu Wenhui, Nie Fan, Jiang Haojing, Zhao Yinan, Zhang Yan, Zhang Zheng, Zhang Jie, Xu Jing, Guo Yuanqiang
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.
Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.
ACS Appl Mater Interfaces. 2024 Dec 11;16(49):68437-68452. doi: 10.1021/acsami.4c16504. Epub 2024 Nov 25.
Hydrophobic chemotherapy drugs face significant challenges in cancer treatment, including low bioavailability, unavoidable toxic side effects, and the development of drug resistance. To address these issues, a multifunctional nanoplatform was developed for cancer therapy, aimed at achieving effective drug delivery and enhancing antitumor efficacy. polysaccharide (PCP), a natural polymer known for its immunomodulatory properties, was utilized as an immunoreactive vector for drug delivery after being cross-linked with 1,4-phenylenebisboronic acid (BDBA). Subsequently, a small-molecule chemotherapy drug, esculetin (EL), was confirmed through density functional theory (DFT) simulations to be encapsulated within the PCP-BDBA nanoparticles via weak interactions. The results demonstrated that the synthesized nanoparticles were spherical, with an average particle size of 162.0 nm. In addition to exhibiting excellent stability, the nanoparticles also displayed pH-responsive drug release properties. experiments indicated that EL@PCP-BDBA NPs exhibited antitumor effects. Furthermore, EL@PCP-BDBA NPs showed superior antitumor activity compared to EL at the cellular level. Additionally, EL@PCP-BDBA NPs were found to increase intracellular reactive oxygen species (ROS) levels, induce cell apoptosis, and suppress cell migration to combat cancer. Meanwhile, EL@PCP-BDBA NPs enhanced immune function . In summary, this study developed a nano-pharmaceutical that combined chemotherapy and immunotherapy functions, which was considered a promising tool for cancer therapy.
疏水性化疗药物在癌症治疗中面临重大挑战，包括生物利用度低、不可避免的毒副作用以及耐药性的产生。为了解决这些问题，开发了一种用于癌症治疗的多功能纳米平台，旨在实现有效的药物递送并提高抗肿瘤疗效。多糖（PCP）是一种以其免疫调节特性而闻名的天然聚合物，在与1,4-亚苯基双硼酸（BDBA）交联后用作药物递送的免疫反应性载体。随后，通过密度泛函理论（DFT）模拟证实，小分子化疗药物七叶亭（EL）通过弱相互作用封装在PCP-BDBA纳米颗粒内。结果表明，合成的纳米颗粒呈球形，平均粒径为162.0 nm。除了具有优异的稳定性外，纳米颗粒还表现出pH响应性药物释放特性。实验表明，EL@PCP-BDBA纳米颗粒具有抗肿瘤作用。此外，在细胞水平上，EL@PCP-BDBA纳米颗粒显示出比EL更强的抗肿瘤活性。此外，发现EL@PCP-BDBA纳米颗粒可增加细胞内活性氧（ROS）水平，诱导细胞凋亡，并抑制细胞迁移以对抗癌症。同时，EL@PCP-BDBA纳米颗粒增强了免疫功能。总之，本研究开发了一种结合化疗和免疫治疗功能的纳米药物，被认为是一种有前途的癌症治疗工具。
