School of Biological and Food Engineering, Hefei Normal University, Hefei, Anhui 230601, PR China; Anhui Engineering Laboratory for Medicinal and Food Homologous Natural Resources Exploration, Hefei, Anhui 230601, PR China; Green Food Rural Revitalization Collaborative Technology Service Center of Anhui, Hefei, Anhui 230601, PR China.
School of Biological and Food Engineering, Hefei Normal University, Hefei, Anhui 230601, PR China.
J Control Release. 2024 Jan;365:74-88. doi: 10.1016/j.jconrel.2023.11.024. Epub 2023 Nov 21.
Metastatic recurrence and postoperative wound infection are two major challenges for breast cancer patients. In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer and wound infection. The hydrogel system was obtained by cross-linking Prussian blue-modified N-carboxyethyl chitosan (PBCEC) and oxidized sodium alginate using the amino and aldehyde groups on the polysaccharides, resulting in the formation of responsive dynamic imine bonds. Conditioned stimulation (e.g., acid microenvironment) enabled the controlled swelling of hydrogels as well as subsequent slow release of loaded doxorubicin (DOX). Additionally, this hydrogel system decomposed endogenous reactive oxygen species into oxygen to relieve the hypoxic tumor microenvironment and promote the healing of infected-wounds. Both in vitro and in vivo experiments demonstrated the synergistic reoxygenation and chemo/photothermal effects of the PB/DOX hydrogel system against metastatic breast cancer and its recurrence, as well as postoperative wound infection. Thus, the combination of reoxygenation and chemo/photothermal therapy represents a novel strategy for treating and preventing tumor recurrence and associated wound infection.
转移性复发和术后伤口感染是乳腺癌患者面临的两大挑战。在这项研究中,开发了一种多功能响应性水凝胶系统,用于转移性乳腺癌和伤口感染的协同再氧合和化疗/光热治疗。该水凝胶系统是通过交联普鲁士蓝修饰的 N-羧乙基壳聚糖(PBCEC)和氧化的海藻酸钠,利用多糖上的氨基和醛基形成响应性动态亚胺键而获得的。条件刺激(例如,酸性微环境)使水凝胶能够控制肿胀,并随后缓慢释放负载的阿霉素(DOX)。此外,该水凝胶系统将内源性活性氧分解成氧气,以缓解缺氧的肿瘤微环境并促进感染伤口的愈合。体外和体内实验均证明了 PB/DOX 水凝胶系统对转移性乳腺癌及其复发和术后伤口感染的协同再氧合和化疗/光热作用。因此,再氧合和化疗/光热治疗的联合使用代表了一种治疗和预防肿瘤复发和相关伤口感染的新策略。