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Imaging-Guided Macrophage-Targeted Nanotheranostics for Rheumatoid Arthritis.

Xinyu Li¹, Shicheng Huo², Zhuocheng Lyu³

¹Department of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China.

ACS Applied Materials & Interfaces

|April 30, 2026

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This summary is machine-generated.

A novel nanoplatform effectively treats rheumatoid arthritis by reprogramming M1 macrophages to M2, promoting bone healing, and enabling real-time imaging for enhanced precision therapy.

Area of Science:

Biomaterials Science
Nanotechnology
Immunology

Background:

Rheumatoid arthritis (RA) involves M1 macrophage infiltration, pro-inflammatory cytokine release, and JAK-STAT/NF-κB pathway activation, leading to cartilage degradation and bone erosion.
Current disease-modifying antirheumatic drugs (DMARDs) like tofacitinib have limited efficacy due to systemic toxicity and poor bone targeting.
Restoring bone homeostasis and managing chronic inflammation in RA remains a significant clinical challenge.

Purpose of the Study:

To develop a multifunctional nanoplatform for targeted codelivery of tofacitinib and osteoimmunomodulatory ions to treat RA.
To investigate the nanoplatform's ability to repolarize M1 macrophages to M2 phenotypes and promote osteoblast differentiation.
To integrate photoacoustic imaging (PAI) for real-time monitoring of therapeutic delivery and treatment efficacy.

Keywords:

Bone remodeling Macrophage polarization Photoacoustic imaging Rheumatoid arthritis Targeted drug delivery Theranostic nanoplatform

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Main Methods:

Fabrication of magnesium-doped mesoporous bioactive glass nanoparticles (Mg-MBGNs) for drug and ion codelivery.
Coating nanoparticles with polydopamine (PDA) for stability and PAI, and functionalizing with folic acid (FA) for targeted macrophage uptake.
In vitro assessment of macrophage phenotype modulation and osteoblast differentiation.
In vivo biodistribution, biosafety, and therapeutic efficacy evaluations.

Main Results:

The MBGN-Tofa@PDA-FA nanoplatform successfully suppressed inflammation by inducing M1-to-M2 macrophage repolarization.
The system synergistically promoted osteoblast differentiation, aiding in bone regeneration.
Polydopamine coating enabled effective photoacoustic imaging for treatment monitoring.
Folic acid targeting ensured selective uptake by macrophages, minimizing systemic toxicity.
In vivo studies confirmed favorable biodistribution and biosafety profiles.

Conclusions:

The developed nanoplatform offers a promising precision theranostic approach for rheumatoid arthritis.
It effectively combines targeted immunomodulation, bone regeneration, and treatment evaluation.
The nanoplatform demonstrates significant potential for clinical translation in RA therapy.