MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis

Abstract

Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA). However, stimulus-responsive therapeutic platform with high specificity for OA basing on the two markers has not been developed yet. We herein demonstrate a new stimuli-responsive theranostic strategy against OA based on a novel multifunctional nano-micelle which is rationally designed and yet readily synthesized. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro an in vivo evidences.

Mechanical loading mitigates osteoarthritis symptoms by regulating the inflammatory microenvironment in a mouse model

“…43 According to clinical and experimental data, there is strong evidence that MMP-13 has a degradative effect on the extracellular matrix and is considered to be an important cofactor or disease mediator in OA. 44,45 In this study, we found that consistent with the increase in M1 macrophages, MMP-13 increased significantly in the OA group. However, after 2 weeks of mechanical loading, there was a reduction in M1 macrophages and the level of MMP-13 was decreased.…”

“…Synovial macrophages are involved in the production of proinflammatory cytokines and MMPs 43 . According to clinical and experimental data, there is strong evidence that MMP‐13 has a degradative effect on the extracellular matrix and is considered to be an important cofactor or disease mediator in OA 44,45 . In this study, we found that consistent with the increase in M1 macrophages, MMP‐13 increased significantly in the OA group.…”

pH-switchable nanozyme cascade catalysis: a strategy for spatial–temporal modulation of pathological wound microenvironment to rescue stalled healing in diabetic ulcer

“…Research into enzyme cascade catalysis may provide insight into potential strategies for the development of desired biocompatible DU microenvironment modulator. Enzymes are natural biomaterials capable of catalyzing various chemical reactions to mediate biological processes [ 26 ]. In living organisms, enzyme cascade systems have been evolved by confining cooperating enzymes within compartments to boost their catalytic performances without the separation of intermediates for spatial–temporal modulation of complex physiological microenvironment [ 27 , 28 ].…”

Targeted treatment for osteoarthritis: drugs and delivery system

“…Qiumei Lan (Lan et al, 2020) et al developed another MMP/pH-responsive DDS loading psoralidin (PSO) which is extracted from pPoralea corylifolia. The MRC-PPL NPs are designed to target cartilage and respond to MMP-13.…”