College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California-Los Angeles, Los Angeles, CA 90095, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, Los Angeles, CA 90095, USA.
J Control Release. 2020 Aug 10;324:750-764. doi: 10.1016/j.jconrel.2020.04.024. Epub 2020 Apr 15.
Sodium selenite (Se)-directed crosslinked hydrogels based on hyaluronic acid (HA)-dopamine (HD), including indocyanine green (ICG), were developed for local therapy of breast cancer. Se can induce polymerization of dopamine (in HD conjugate) by making alkaline pH value, coordinate with the functional groups of HD, and kill cancer cells by pro-oxidant effects. ICG can be entrapped in the crosslinked HD/Se hydrogel network and long lasting photothermal efficacies can be maintained for cancer therapy. HD conjugate was synthesized via an amide linkage between carboxylic acid group of HA and amine group of dopamine. HD/Se gel was fabricated by covalent bonding of dopamine group (in HD conjugate) and the coordination between selenium and functional groups of HD. Controlled rheological properties of HD/Se/ICG gel may provide easy injectability and slow biodegradability. Sufficient photothermal efficiencies were acquired after near-infrared (NIR) laser irradiation. HD/Se/ICG gel structure was remained in the mouse for 2 weeks and severe systemic toxicities were not observed in blood and histological assays. Intratumoral injection of HD/Se/ICG gel with NIR laser irradiation provided the most efficient tumor growth inhibition capability without severe systemic toxicities. HD/Se/ICG hydrogel structure can be introduced as a promising multifunctional platform for local therapy of breast cancers.
基于透明质酸（HA）-多巴胺（HD）的硒诱导交联水凝胶，包括吲哚菁绿（ICG），被开发用于乳腺癌的局部治疗。硒可以通过产生碱性 pH 值来诱导多巴胺（在 HD 缀合物中）聚合，与 HD 的官能团配位，并通过促氧化剂作用杀死癌细胞。ICG 可以被包埋在交联的 HD/Se 水凝胶网络中，并能保持长时间的光热疗效以用于癌症治疗。HD 缀合物是通过 HA 的羧酸基团和多巴胺的胺基团之间的酰胺键合成的。HD/Se 凝胶是通过多巴胺基团（在 HD 缀合物中）的共价键合以及硒与 HD 的官能团之间的配位来制备的。HD/Se/ICG 凝胶的可控流变性能可能提供易于注射和缓慢的生物降解性。在近红外（NIR）激光照射后获得了足够的光热效率。HD/Se/ICG 凝胶结构在小鼠体内保持了 2 周，并且在血液和组织学分析中没有观察到严重的全身毒性。NIR 激光照射下瘤内注射 HD/Se/ICG 凝胶提供了最有效的肿瘤生长抑制能力，而没有严重的全身毒性。HD/Se/ICG 水凝胶结构可以作为一种有前途的多功能平台，用于局部治疗乳腺癌。
