Remodeling Periodontitis Microenvironment for Osteogenesis by Using a Reactive Oxygen Species-Cleavable Nanoplatform

Abstract

Modestly removing the excessive reactive oxygen species (ROS) plays a crucial part in regulating the microenvironment of periodontitis and provides a favorable condition for osteogenesis. However, the current strategy in scavenging ROS is incontrollable, greatly limiting the outcome of periodontitis. Herein, we introduced a controllable ROS-scavenging nanoplatform by encasing N-Acetylcysteine (NAC, (a famous ROS scavenger) into a tailor-made ROS-cleavable amphiphilic polymer nanoparticles (PEG-ss-PCL NSs) as an intracellular delivery carrier. The existing ROS in the inflammatory microenvironment facilitated the polymer degradation via breakage of the thioketal bonds, then led to the encapsulated NAC release. The NAC eliminated all ROS induced by LPS, while PssL-NAC adjusted the ROS level to a litter higher than the control group. The percentage of apoptotic cells cultured with NAC and PssL-NAC decreased observably compared with cells cultured with 10 µg/ml LPS. The microenvironment regulated by PssL-NAC was very suitable for osteogenic differentiation from the results of PCR and Western blot, which exhibited a higher expression level of BMP2, Runx2, and PKA. The ALP activity and Alizarin red S staining showed consistent results. Additionally, the injection of NAC and PssL-NAC into the periodontitis area could alleviate the tissue destruction induced by ligation of the maxillary second molar. The PssL-NAC showed a better ability to decrease the osteoclast activity and inflammation, consequently improving the restoration of destructed tissue. Our study suggests that ROS responsive polymer nanoparticles loading NAC (PssL-NAC) can be new promising material for periodontitis treatment.