Triptolide Self-Assembling Nanoparticles Engineering with Modified Erythrocyte Membranes for Targeting and Remodeling Inflammatory Microenvironment in Arthritis

04 August 2020, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease causing severe joint damage, disability and decreased quality of life. Pathologically, numerous blood-derived cells infiltrating in synovium and cytokine secret necessitating formation of new blood vessels to generate pannus together form an inflammatory microenvironment. Triptolide with immunosuppressive activities is a potential drug to treat RA. However, it is still lack of an effective targeting system to deliver triptolide to RA site safely. Herein an inflammatory microenvironment targeting and remodeling nanoplatform is developed to achieve significantly effective RA treatment. In this system we synthesized a self-assembling triptolide nanoparticles (TPNs) mediated by dipeptide diphenylalanine which is the simplest self-assembly building block, then TPNs were entrapped by mannose-modified erythrocyte membranes to form engineering manRTPNs. For targeting, the immunological molecule of erythrocytes was firstly introduced to target T cells by ligand binding of LFA-3/LFA-2, and the coated mannose modified erythrocyte membrane also conferred the capacity of targeting to macrophages by mannose and its receptor CD206; for remodeling inflammatory microenvironment, TPNs could selectively exert its suppressive effects on different cells of RA including lymphocytes and synovial fibroblasts. In collagen
induced arthritis mice, manRTPNs showed excellent targeting effect and prolonged accumulation at inflamed joint. After manRTPNs treatment, swollen paws of CIA considerably shrunk to normal, boss loss even recovered healthy level and cartilage preserved at synovium cavity, because of systemically conventional cytokine reduction and expression shift of core genes in networks of RA microenvironment. Therefore, this well-defined manRTPNs might be a well promising systematic therapeutic agent for RA.

Keywords

Triptolide
Nanodrug
self-assembly
Immuno-Microenvironment Remodeling
Rheumatoid Arthritis
Cytokine storm
viral infections

Supplementary materials

Title
Description
Actions
Title
manuscript-update 20200804
Description
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.