Chi Runrun, Pan Luqi, Yang Ziwei, Yang Xiao, Xia Hangbin, Lin Dan, Hao Jiahui, Si Xiaoqin, Yan Dongxue, Li Huili, Shi Changcan, Wang Yuqin, Li Wenzhong
School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
Int J Biol Macromol. 2025 Jan;284(Pt 2):138118. doi: 10.1016/j.ijbiomac.2024.138118. Epub 2024 Nov 26.
Hyaluronic acid (HA) nanogels have attracted widespread attention, aiming to improve cancer treatment paradigms and overcome the limitations of free-form drugs. However highly hydrophilic nature of HA nanogels limits their potential application where amphiphilic interactions are required for the delivery of hydrophobic drugs. In this study, we developed amphiphilic structure oxaliplatin (OXA) loaded oligo-hyaluronic acid (oHA)-PEG-Octane nanogel using stable disulfide bonds with ultrasonic re-emulsion method. 1,8-Mercaptooctane present in the organic phase underwent crosslinking with sulfhydryl groups conjugated on oHA and PEG in the inner aqueous phase through interfacial reactions, resulting in the formation of an amphiphilic structure of the nanogels. The nanogels demonstrated uniform size, stability, excellent biocompatibility, and achieved a high drug-loading capacity of 10.8 %. OXA NGs targeted tumor cells through CD44-mediated endocytosis, disassembled under the influence of high glutathione (GSH) levels within the tumor microenvironment (TME) and released OXA inside the reductive cytosol to trigger immunogenic cell death (ICD) of tumor cells. In vivo experiments showed OXA NGs could inhibit tumor growth. Furthermore, the amphiphilic hyaluronic acid nanohydrogel may have clinical potential due to its ability to accommodate various therapeutic agents; therefore, OXA NGs are a potential candidate for clinical translation.
透明质酸（HA）纳米凝胶已引起广泛关注，旨在改善癌症治疗模式并克服游离形式药物的局限性。然而，HA纳米凝胶的高亲水性限制了它们在递送疏水药物需要两亲相互作用的潜在应用。在本研究中，我们使用稳定的二硫键通过超声再乳化法制备了负载两亲结构奥沙利铂（OXA）的低聚透明质酸（oHA）-聚乙二醇-辛烷纳米凝胶。有机相中存在的1,8-巯基辛烷通过界面反应与内水相中与oHA和聚乙二醇共轭的巯基发生交联，从而形成纳米凝胶的两亲结构。该纳米凝胶表现出尺寸均匀、稳定性好、生物相容性优异，并实现了10.8%的高载药量。OXA纳米凝胶通过CD44介导的内吞作用靶向肿瘤细胞，在肿瘤微环境（TME）中高谷胱甘肽（GSH）水平的影响下分解，并在还原性胞质溶胶中释放OXA以触发肿瘤细胞的免疫原性细胞死亡（ICD）。体内实验表明OXA纳米凝胶可以抑制肿瘤生长。此外，两亲性透明质酸纳米水凝胶由于其容纳各种治疗剂的能力可能具有临床潜力；因此，OXA纳米凝胶是临床转化的潜在候选者。
