Zheng Xiaoyi, Wu Hang, Wang Shige, Zhao Jiulong, Hu Lianghao
Postgraduate Training Base in Shanghai Gongli Hospital, Ningxia Medical University, Pudong New Area, No. 219 Miao Pu Road, Shanghai 200135, China.
Department of Gastroenterology, Changhai Hospital, Naval Military Medical University, No. 168 Changhai Road, Shanghai 200433, China.
Gels. 2023 May 31;9(6):452. doi: 10.3390/gels9060452.
In recent years, multifunctional hydrogel nanoplatforms for the synergistic treatment of tumors have received a great deal of attention. Here, we prepared an iron/zirconium/polydopamine/carboxymethyl chitosan hydrogel with Fenton and photothermal effects, promising for future use in the field of synergistic therapy and prevention of tumor recurrence. The iron (Fe)-zirconium (Zr)@ polydopamine (PDA) nanoparticles were synthesized by a simple one-pot hydrothermal method using iron (III) chloride hexahydrate (FeCl•6HO), zirconium tetrachloride (ZrCl), and dopamine, followed by activation of the carboxyl group of carboxymethyl chitosan (CMCS) using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/N(4)-hydroxycytidine (NHS). Finally, the Fe-Zr@PDA nanoparticles and the activated CMCS were mixed to form a hydrogel. On the one side, Fe ions can use hydrogen peroxide (HO) which is rich in the tumor microenvironment (TME) to produce toxic hydroxyl radicals (•OH) and kill tumor cells, and Zr can also enhance the Fenton effect; on the other side, the excellent photothermal conversion efficiency of the incorporated PDA is used to kill tumor cells under the irradiation of near-infrared light. The ability of Fe-Zr@PDA@CMCS hydrogel to produce •OH and the ability of photothermal conversion were verified in vitro, and swelling and degradation experiments confirmed the effective release and good degradation of this hydrogel in an acidic environment. The multifunctional hydrogel is biologically safe at both cellular and animal levels. Therefore, this hydrogel has a wide range of applications in the synergistic treatment of tumors and the prevention of recurrence.
近年来，用于肿瘤协同治疗的多功能水凝胶纳米平台受到了广泛关注。在此，我们制备了一种具有芬顿和光热效应的铁/锆/聚多巴胺/羧甲基壳聚糖水凝胶，有望在协同治疗和预防肿瘤复发领域得到应用。采用简单的一锅水热法，以六水合氯化铁（FeCl•6H₂O）、四氯化锆（ZrCl₄）和多巴胺合成铁（Fe）-锆（Zr）@聚多巴胺（PDA）纳米颗粒，随后用1-(3-二甲基氨基丙基)-3-乙基碳二亚胺盐酸盐（EDC）/N-(4-羟基丁二酰亚胺)（NHS）活化羧甲基壳聚糖（CMCS）的羧基。最后，将Fe-Zr@PDA纳米颗粒与活化的CMCS混合形成水凝胶。一方面，Fe离子可利用肿瘤微环境（TME）中丰富的过氧化氢（H₂O₂）产生有毒的羟基自由基（•OH）并杀死肿瘤细胞，Zr也能增强芬顿效应；另一方面，掺入的PDA具有优异的光热转换效率，可在近红外光照射下杀死肿瘤细胞。体外验证了Fe-Zr@PDA@CMCS水凝胶产生•OH的能力和光热转换能力，溶胀和降解实验证实了该水凝胶在酸性环境中的有效释放和良好降解性能。这种多功能水凝胶在细胞和动物水平上均具有生物安全性。因此，这种水凝胶在肿瘤协同治疗和预防复发方面具有广泛的应用前景。
