Xu Zhilang, Yang Die, Long Tao, Yuan Lun, Qiu Shi, Li Defu, Mu Changdao, Ge Liming
Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610065, PR China.
Carbohydr Polym. 2022 Feb 1;277:118827. doi: 10.1016/j.carbpol.2021.118827. Epub 2021 Nov 10.
pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.
pH响应性纳米颗粒（NPs）已成为一种有效的抗肿瘤药物递送系统，可促进药物在肿瘤中的积累，并在肿瘤酸性微环境中选择性释放药物。在此，我们开发了一种基于两亲性修饰羟乙基淀粉（HES）的新型pH敏感型抗肿瘤药物递送纳米载体。首先用亲水性咪唑和疏水性胆固醇对HES进行修饰，得到两亲性聚合物（IHC）。然后，IHC可自组装以包裹阿霉素（DOX）并形成载阿霉素纳米颗粒（DOX/IHC NPs），其在储存一周时显示出良好的稳定性，且对DOX具有酸性敏感的长期持续释放性能。结果，癌细胞内吞DOX/IHC NPs后可将阿霉素持续释放到细胞质和细胞核中，从而有效杀死癌细胞。此外，DOX/IHC NPs可有效富集于肿瘤组织中，与游离阿霉素相比，显示出更强的肿瘤生长抑制效果。总体而言，我们基于两亲性修饰HES的纳米颗粒作为癌症化疗的药物递送系统具有巨大潜力。
