Integration of Tumor Elimination And Tissue Regeneration via Selective Manipulation of Physiological Microenvironments Based on Intelligent Nanocomposite Hydrogel for Postoperative Treatment of Malignant Melanoma |
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Authors: | Li Chen Tianfeng Yang Lin Weng Xiaowei Chang Jie Liu Xiuhong Peng Cheng Cheng Peng Han Yanmin Zhang Xin Chen |
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Affiliation: | 1. Department of Chemical Engineering, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an, 710049 P. R. China;2. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061 P.R. China;3. Department of Otorhinolaryngology-Head and Neck Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061 P. R. China |
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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 H2O2 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 offered an promising strategy for postoperative treatment of various tumors. |
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Keywords: | copper dependent nanocatalytic medicine effective therapy of malignant melanoma intracellular copper regulation on-demand manipulation of microenvironments promoted regeneration of skin tissues |
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