Arthritic Microenvironment Actuated Nanomotors for Active Rheumatoid Arthritis Therapy

Abstract

Increasing O 2 demand and excessive ROS production are the main features of arthritic microenvironment in rheumatoid arthritis (RA) joints and further play pivotal roles in inflammation exacerbation. In this work, a system of in situ regulation of arthritic microenvironment based on nanomotor strategy is proposed for active RA therapy. The synthesized MnO 2 -motors enable catalytic regulation of RA microenvironment by consuming the overproduced H 2 O 2 and generating O 2 synergistically. The generated O 2 under H 2 O 2 -rich conditions functions as inflammation detector, propellant for enhanced diffusion, as well as ameliorator for the hypoxic synovial microenvironment. Owing to O 2 generation and inflammation scavenging, the MnO 2 -motors block the re-polarization of pro-inflammatory macrophages, which results in significantly decreased secretion of multiple pro-inflammatory cytokines both in vitro and in vivo. In addition, intra-articular administration of MnO 2 -motors to collagen-induced arthritis rats (CIA rats) effectively alleviates hypoxia, synovial inflammation, bone erosion, and cartilage degradation in joints. Therefore, the proposed arthritic regulation strategy shows great potential to seamlessly integrate basic research of RA with clinical translation.

Nanozyme-Based Remodeling of Disease Microenvironments for Disease Prevention and Treatment: A Review

“…Meanwhile, in vitro experiments confirmed that the nanozyme could induce the transformation of macrophages from the M1 subtype to the M2 subtype. Xu et al 209 reported a H 2 O 2 -driven MnO 2 nanozyme based on the arthritis microenvironment, which could alleviate hypoxia and remove ROS. Improvement of the local microenvironment inhibits phenotypic polarization of the M1-type macrophages, and thus reduces the inflammatory response (Figure 12A).…”

“…(A) H 2 O 2 -driven MnO 2 nanozyme based on the arthritis microenvironment. Adapted under the CC BY license from ref . Copyright 2022 The Authors.…”

Swarms of Enzyme‐Powered Nanomotors Enhance the Diffusion of Macromolecules in Viscous Media

“…An intriguing strategy involves the creation of MnO 2 -nanomotors for the purpose of active rheumatoid arthritis therapy. [18] While this innovative material shows promise, its reliance on peroxide raises concerns about potential impacts on cell viability. Moreover, the present study has concentrated on the analysis of NM mobility in aqueous surroundings, extending up to 10 mm H 2 O 2 .…”

Light‐Driven Biomimetic Nanomotors for Enhanced Photothermal Therapy

“…[20,21] MNMs are micro-/nanoscale devices capable of converting different forms of energy sources into mechanical force, hence producing autonomous motion to fulfill the designated tasks. [22][23][24][25] The propelling force is expected to endow MNMs with the kinetic motion to overcome the biological barriers, [26] for instance, biofouling, [27] blood-brain barrier, [28] mucosal, [29] and dense extracellular matrix. [30] However, once entering the bloodstream, MNMs may be rapidly identified by mononuclear phagocytes and then eliminated from systemic blood circulation.…”