Integration of Tumor Elimination And Tissue Regeneration via Selective Manipulation of Physiological Microenvironments Based on Intelligent Nanocomposite Hydrogel for Postoperative Treatment of Malignant Melanoma

作者：Li Chen, Tianfeng Yang, Lin Weng, Xiaowei Chang, Jie Liu, Xiuhong Peng, Cheng Cheng, Peng Han, Yanmin Zhang, Xin Chen · 发表于：Advanced Functional Materials · 年份：2023 · DOI：10.1002/adfm.202304394 · 被引用次数：23 · 研究领域：Nanoplatforms for cancer theranostics、Extracellular vesicles in disease、Immune cells in cancer

Abstract Tumor residue and tissue damage normally occurred after surgical treatment of malignant melanoma, and the effective postoperative therapy is still a challenge because the treatment requests simultaneous but opposite manipulation of tumor cells and healthy cells. Herein, MBGP‐Gel, a thermosensitive and biodegradable hydrogel incorporating S‐nitrosoglutathione (GSNO) loaded and N‐aminoethyl‐N’‐benzoyl thiourea (BTU) modified MSNs (MBGP NPs), was designed to utilize the significant difference of copper content between tumor cells and healthy cells to regulate various physiological microenvironments for integrative therapy of tumor elimination, metastasis inhibition and tissue regeneration. The MBGP‐Gel underwent sol‐gel transformation at body temperature after injection, and continuously released MBGP nanoparticles. In tumor cells, these nanoparticles would chelate the excess copper to inhibit the tumor migration. Meanwhile, copper was reduced to cuprous, which further catalyzed the abundant H 2 O 2 and GSNO to produce oxygen species (ROS) and nitric oxide (NO), respectively. The ROS and the reaction product of ROS and NO (ONOO) would significantly damage the tumor tissue. In contrast, MBGP nanoparticles entered healthy cells only generate appropriate amount of NO to accelerate tissue healing. Both in vitro and in vivo results showed that the nanocomposite hydrogel could inhibit the growth and metastasis of malignant melanoma and promote the skin regeneration, which off...