Acta Biomaterialia ( IF 9.4 ) Pub Date : 2021-05-16 , DOI: 10.1016/j.actbio.2021.05.006 Guoru Dai 1 , Lu Sun 1 , Jing Xu 1 , Guizhen Zhao 1 , Zheng Tan 1 , Chen Wang 1 , Xiaolian Sun 2 , Keming Xu 3 , Wenying Zhong 4
|
Hydrogels have drawn considerable attention in the field of drug delivery, yet their poor mechanical strength and uncontrollable drug release behavior have hindered further applications in clinical practice. Taking utility of metal–ligand coordination for structurally reinforcing the hydrogel network, we report design and synthesis of magnetic nanocomposite hydrogels (HA-DOPA·MNPs) that are crosslinked by DOPA–Fe(III) coordination existing between dopamine-conjugated hyaluronan (HA-DOPA) and iron oxide magnetic nanoparticles (MNPs). The MNPs in the nanocomposite hydrogel not only serve as structural crosslinkers, but also facilitate magnetic hyperthermia and on-demand release of doxorubicin (DOX) in HA-DOPA·MNPs/DOX hydrogels, for release rate of DOX accelerates when external alternating magnetic field (AMF) is ON, and it restores to a slow pace when AMF is OFF. Importantly, HA-DOPA·MNPs/DOX hydrogel shows a longer retention time than HA-DOPA/DOX gel or DOX solution in vivo. Further experiments confirm the efficacious anticancer potency of HA-DOPA·MNPs/DOX in vitro and in vivo, that is mediated by a combination therapy consisting of chemotherapy (DOX) and hyperthermia (MNPs). In contrast, single-modality treatment (DOX or hyperthermia only) fails to show an equivalent efficacy at the same dose.
Statement of significance
This study reports the design of a class of magnetic nanocomposite hydrogel (HA-DOPA·MNPs) that was structurally reinforced by DOPA–Fe (III) coordination between HA-DOPA and iron oxide MNPs. On one hand, MNPs served as crosslinking centers for structurally reinforcing the nanocomposite hydrogel; on the other hand, MNPs facilitated temperature rise under an external MNPs, which prompted on-demand drug release as well as a combination therapy. Comparing to single modality treatment (chemotherapy or hyperthermia alone), the HA-DOPA·MNPs/DOX formulation with AMF demonstrated better efficacy against proliferation of tumor cells (A375) both in vitro and in vivo. We believe that design of HA-DOPA·MNPs/DOX hydrogel in this report provides a general approach to fabricate structurally-reinforced nanocomposite hydrogels for on-demand drug delivery and efficacious combination therapy.
中文翻译：
用于按需给药和有效联合治疗的儿茶酚-金属配位介导的纳米复合水凝胶
水凝胶在药物递送领域引起了广泛关注，但其机械强度差和药物释放行为不可控，阻碍了其在临床实践中的进一步应用。利用金属-配体配位在结构上增强水凝胶网络，我们报告了磁性纳米复合水凝胶（HA-DOPA·MNPs）的设计和合成，这些水凝胶通过多巴胺偶联透明质酸（HA- DOPA) 和氧化铁磁性纳米粒子 (MNP)。纳米复合水凝胶中的 MNPs 不仅作为结构交联剂，而且有助于磁热疗和 HA-DOPA·MNPs/DOX 水凝胶中多柔比星 (DOX) 的按需释放，因为当外部交变磁场时，DOX 的释放速率加快。 AMF) 开启，当 AMF 关闭时，它恢复到慢速。重要的是，HA-DOPA·MNPs/DOX 水凝胶显示出比 HA-DOPA/DOX 凝胶或 DOX 溶液更长的保留时间体内。进一步的实验证实了 HA-DOPA·MNPs/DOX在体外和体内的有效抗癌效力，这是由化学疗法 (DOX) 和热疗 (MNPs) 组成的联合疗法介导的。相比之下，单一模式治疗（仅 DOX 或热疗）在相同剂量下无法显示出等效的疗效。
重要性陈述
本研究报告了一类磁性纳米复合水凝胶（HA-DOPA·MNPs）的设计，该凝胶通过 HA-DOPA 和氧化铁 MNPs 之间的 DOPA-Fe（III）配位在结构上得到增强。一方面，MNPs 作为交联中心在结构上增强纳米复合水凝胶；另一方面，MNPs 在外部 MNPs 下促进温度升高，这促使按需药物释放以及联合治疗。与单一方式治疗（单独的化疗或热疗）相比，HA-DOPA·MNPs/DOX 制剂与 AMF在体外和体内均表现出更好的抗肿瘤细胞（A375）增殖功效. 我们相信本报告中 HA-DOPA·MNPs/DOX 水凝胶的设计提供了一种通用的方法来制造结构增强的纳米复合水凝胶，用于按需给药和有效的联合治疗。
京公网安备 11010802027423号