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通过逆电子需求Diels-Alder(IEDDA)点击化学制备用于光热-光动力抗肿瘤治疗的近红外响应性藻酸盐/羧甲基纤维素水凝胶

Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal-Photodynamic Anti-Tumor Therapy.

作者信息

Rizwan Ali, Ali Israr, Jo Sung-Han, Vu Trung Thang, Gal Yeong-Soon, Kim Yong Hyun, Park Sang-Hyug, Lim Kwon Taek

机构信息

Department of Smart Green Technology Engineering, Pukyong National University, Busan 48513, Republic of Korea.

Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Republic of Korea.

出版信息

Gels. 2023 Dec 7;9(12):961. doi: 10.3390/gels9120961.

Abstract

Novel chemically cross-linked hydrogels derived from carboxymethyl cellulose (CMC) and alginate (Alg) were prepared through the utilization of the norbornene (Nb)-methyl tetrazine (mTz) click reaction. The hydrogels were designed to generate reactive oxygen species (ROS) from an NIR dye, indocyanine green (ICG), for combined photothermal and photodynamic therapy (PTT/PDT). The cross-linking reaction between Nb and mTz moieties occurred via an inverse electron-demand Diels-Alder chemistry under physiological conditions avoiding the need for a catalyst. The resulting hydrogels exhibited viscoelastic properties (G' ~ 492-270 Pa) and high porosity. The hydrogels were found to be injectable with tunable mechanical characteristics. The ROS production from the ICG-encapsulated hydrogels was confirmed by DPBF assays, indicating a photodynamic effect (with NIR irradiation at 1-2 W for 5-15 min). The temperature of the ICG-loaded hydrogels also increased upon the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility assessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Furthermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells after NIR exposure.

摘要

通过利用降冰片烯(Nb)-甲基四嗪(mTz)点击反应,制备了源自羧甲基纤维素(CMC)和藻酸盐(Alg)的新型化学交联水凝胶。这些水凝胶被设计用于从近红外染料吲哚菁绿(ICG)产生活性氧(ROS),用于联合光热和光动力疗法(PTT/PDT)。在生理条件下,Nb和mTz部分之间的交联反应通过逆电子需求狄尔斯-阿尔德化学发生,无需催化剂。所得水凝胶表现出粘弹性特性(G'~492 - 270 Pa)和高孔隙率。发现这些水凝胶可注射且具有可调的机械特性。通过DPBF测定法证实了包封ICG的水凝胶产生ROS,表明具有光动力效应(在1 - 2 W的近红外照射下照射5 - 15分钟)。加载ICG的水凝胶的温度在近红外照射下也会升高,以光热方式根除肿瘤细胞。体外细胞相容性评估显示CMC-Nb和Alg-mTz对HEK-293细胞无毒。此外,加载ICG的水凝胶在近红外照射后有效抑制了Hela细胞的代谢活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b55/10742702/3428169fa42a/gels-09-00961-sch001.jpg

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