Native nanodiscs from blood inhibit pulmonary fibrosis

Abstract

Blood is a treasure trove whose constituents have attracted increasing attention for use in understanding and controlling disease. However, the functions of blood, especially with regard to its composition at the nanoscale, remain largely unknown. Inspired by exosomes and lipoproteins, the present work isolated and characterized biotic nanodiscs from human blood (BNHBs) using multiple techniques. The isolated BNHBs had diameters of 10-30 nm and a thicknesses of approximately 2.9 nm. The BNHB concentration in blood peaked at 34.5 ± 5.19 mg/mL (20-fold higher than that of high-density lipoproteins and exosomes). BNHBs had high biocompatibility, facile cell internalization and strong biological control of pulmonary fibrosis. The BNHBs were hybrids of many metalloproteins and metabolites and contained a few functional proteins similar to lipoproteins or exosomal proteins. BNHBs inhibited transforming growth factor-beta 1 (TGF-β1)-induced fibrosis damage in human embryonic lung fibroblasts (HELFs) by inhibiting the expression of α-smooth muscle actin and collagen-1 protein. BNHBs also intensively bound TGF-β1 to inhibit TGF-β1 activity in fibrogenesis. BNHBs successfully reduced pulmonary inflammation and collagen deposition in a mouse model, preventing pulmonary fibrosis. Applying the protective properties of nanodiscs may be a novel therapeutic approach for pulmonary and other diseases.

Keywords: Antioxidant; Blood; Fibrogenesis; Nanodiscs; Nanomedicine; TGF-β1.