Effects of ROS-Sensitive Nanoparticles Loaded with Interstitial Cell Derived Factors on Vascular Smooth Cell Adhesion, Proliferation, and Endothelialization

Abstract

Local high concentrations of stromal cell-derived factor 1 (SDF-1) attract and trap stem cells to involve in the vascular repair when the skin is damaged. In this research, mercaptan ketone polymer (PRGY) was selected as a nano-carrier to prepare ROS-sensitive nanoparticles (NPs) loaded with SDF-1 by means of volatilization of a complex emulsion solvent. The NPs were characterized by a transmission electron microscope (TEM) and a particle size (PS) analyzer, the protein content of the NPs was evaluated by a BCA method, the cytotoxicity was evaluated by CCK8, and the NPs were subjected to the in vitro release (IVR) test. An acute mouse wound model was established, the pathological effect of NP solution on major organs of mice was observed by HE staining after intravenous injection, and the effect of targeted release of NP on animal model was evaluated. To analyze the effect of NPs on wound healing, the mouse models were rolled into different groups. They were sacrificed two weeks after the wound healing was completed, the blood vessels were fixed with perfusion solution, and the common artery where the wound was located was taken for follow-up study. The results suggested that the NPs exhibited a PS of 122.57±18.33 nm, a loading rate of 1.7%, and spherical and uniform surfaces. The IVR tests showed that the NPs could release rapidly under high ROS conditions. The wound model of mice was established, and the injection of NP solution revealed that it could target the wound area. The healing speed in the NP group was the fastest (P <0.05). Smooth muscle cells (SMCs) and endothelial cells (ECs) were isolated from common artery, and proliferation of them in the NP group was found to be obvious (P <0.05), and the adhesion of vascular SMCs could be accelerated at the same time.