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

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.

Intelligent gold nanocluster for effective treatment of malignant tumor via tumor-specific photothermal–chemodynamic therapy with AIE guidance

“…In contrast, the nanoparticles without the copper chelator (AuTF) caused a negligible change in the level of copper ions even after 12 h of co-incubation. In order to distinguish the change in copper ions and cuprous ions, we further investigated the intracellular Cu + level before and after AuNTF treatment; the typical Cu + indicator (bathocuproine) and UV–Vis spectra were employed according to our previous studies [ 56 , 59 , 60 ]. The bathocuproine can specifically react with Cu + to form a chromogenic complex, which performed a characteristic absorption at 480 nm.…”