Minimally Invasive Antitumor Therapy Using Biodegradable Nanocomposite Micellar Hydrogel with Functionalities of NIR-II Photothermal Ablation and Vascular Disruption.

Abstract

A powerful minimally invasive approach holds great promise toward the treatment of solid tumors in the aims of reducing the systemic toxicity of drugs and the risk of infections in surgeries. Herein, we design a PLEL-based thermosensitive nanocomposite micellar hydrogel delivery platform, in which the two-dimensional nanosheet-based photothermal agent and vascular disrupting agent (combretastatin A4, CA4) are loaded for synergistic antitumor therapy. Ultrathin Ti3C2 MXene with a thickness less than 5 nm is synthesized through a combination of an acid/alkaline etching method. The obtained Ti3C2/CA4@PLEL micellar hydrogel exhibits a loading efficiency of 99.6%, long-acting sustained release, and favorable photothermal effect in the NIR-II biowindow (a photothermal conversion efficiency of 41.4% at 1064 nm). Besides, the CA4-loaded micelles allow efficient cellular uptake for drugs and selectively kill the tumor vascular endothelial cells using the human umbilical vein endothelial cells (HUVECs) as a cell model. Moreover, the in vivo studies demonstrate that the combinational group of the Ti3C2/CA4@PLEL micellar hydrogel eliminates the solid tumor thoroughly from an initial volume of 200 mm3, superior to other groups. This work highlights the potential of the biodegradable micellar hydrogel networks assembled with multifunctional objects for antitumor therapy.