Cell Membrane-Coated Nanotherapeutics for the Targeted Treatment of Acute and Chronic Colitis.

Abstract

Integrin α4β1 and α4β7 are overexpressed in macrophages and leukocytes and play important roles in mediating cell homing and recruitment to inflammatory tissues. Herein, to enhance the targeting ability of nanotherapeutics for inflammatory bowel disease (IBD) treatment, cyclosporine A-loaded nanoparticles (CsA NPs) were coated with macrophage membranes (MM-CsA NPs) or leukocyte membranes (LM-CsA NPs). In vitro experiments demonstrated that the physicochemical properties of the nanotherapeutics (e.g., size, zeta potential, polymer dispersity index, and drug release profiles) did not obviously change after cell membrane coating. However, integrin α4β1 and α4β7 were expressed in MM-CsA NPs and LM-CsA NPs, respectively, which significantly inhibited normal macrophage phagocytosis and obviously increased uptake by proinflammatory macrophages and endothelial cells. In vivo experiments verified that cell membrane-coated nanotherapeutics have longer retention times in inflammatory intestinal tissues. Importantly, LM-CsA NPs significantly mitigated weight loss, alleviated colon shortening, decreased disease activity indices (DAIs), and promoted colon tissue repair in acute and chronic colitis model mice. Furthermore, LM-CsA NPs significantly decreased the expression of inflammatory factors such as TNF-α and IL-6 and increased the expression of gut barrier-related proteins such as E-cadherin, ZO-1, and occludin protein in colitis mice.