Bioactive phosphorus dendrimers deliver protein/drug to tackle osteoarthritis via cooperative macrophage reprogramming.

Biomaterials

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China. Electronic address:

Published: December 2024

AI Article Synopsis

  • - The study focuses on reprogramming synovial macrophages and creating an immune environment that supports bone and cartilage growth to address osteoarthritis (OA) effectively.
  • - Researchers developed a nanosystem using bioactive phosphorus dendrimers loaded with catalase (CAT) and quercetin (Que), which helps shift macrophages to a beneficial anti-inflammatory state and supports cell health.
  • - When tested on an OA mouse model, this system reduced cartilage damage, bone erosion, and inflammation, and it also showed potential in human-derived cells by promoting similar positive changes in macrophages from OA patients.

Article Abstract

Reprogramming imbalanced synovial macrophages and shaping an immune microenvironment conducive to bone and cartilage growth is crucial for efficient tackling of osteoarthritis (OA). Herein, we present a co-delivery nanosystem based on generation 2 (G2) hydroxyl-terminated bioactive phosphorus dendrimers (G2-OH) that were loaded with both catalase (CAT) and quercetin (Que). The created G2-OH/CAT@Que complexes exhibit a uniformly distributed spherical morphology with a size of 138.8 nm, possess robust stability, and induce macrophage reprogramming toward anti-inflammatory M2 phenotype polarization and antioxidation through cooperative CAT-catalyzed oxygen generation, Que-mediated mitochondrial homeostasis restoration, and inherent immunomodulatory activity of dendrimer. Such macrophage reprogramming leads to chondrocyte apoptosis inhibition and osteogenic differentiation of bone mesenchymal stem cells. Administration of G2-OH/CAT@Que to an OA mouse model results in attenuation of pathological features such as cartilage degeneration, bone erosion, and synovitis through oxidative stress alleviation and inflammatory factor downregulation in inflamed joints. Excitingly, the G2-OH/CAT@Que also polarized macrophages in adherent effusion monocytes (AEMs) extracted from joint cavity effusions of OA patients to M2 phenotype and downregulated reactive oxygen species levels in AEMs. This study suggests a promising nanomedicine formulation of phosphorus dendrimer-based co-delivery system to effectively tackle OA through the benefits of full-active ingredients of dendrimer, drug, and protein.

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Source
http://dx.doi.org/10.1016/j.biomaterials.2024.122999DOI Listing

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