New progress has been made in photothermal reprogramming of synovial M1 macrophages for reversing temporomandibular joint osteoarthritis.
Researchers Huang Li and Wei Han from the Affiliated Stomatological Hospital of Nanjing University Medical School have achieved new advances in the field of oral and maxillofacial research. Their findings were published in the international top journal “ Journal of Nanobiotechnology” (IF = 14.7, CAS Q1 top journal).
This study provides new insights into precise photothermal immunomodulation of M1 macrophages and the development of an actively targeted nanoplatform for spatially controlled treatment and systemic protection of temporomandibular joint osteoarthritis.
Temporomandibular joint osteoarthritis (TMJOA) is a common degenerative disease characterized by progressive synovial inflammation, cartilage degradation, and subchondral bone destruction. Although thermal therapy (such as hot compresses) is commonly used clinically to relieve symptoms, its underlying active immune regulatory mechanisms remain unclear. In addition, traditional heating approaches, such as heat packs, are limited by poor tissue penetration and imprecise temperature control. This study aimed to investigate the immune reprogramming effects of precisely controlled local photothermal therapy on synovial M1 macrophages and develop an actively targeted nanoplatform (FA-Y8 NPs) for spatially precise intervention and systemic joint protection in TMJOA.
However, conventional non-specific thermal therapy cannot selectively target lesions, while excessive heating can cause severe cytotoxicity. A key challenge for precise disease intervention is demonstrating that the nanoparticles can actively target M1 macrophages through highly expressed folate receptors and achieve accurate, mild photothermal regulation in deep tissues under near-infrared irradiation without damaging normal tissues.
To verify whether the nanoparticles could specifically accumulate in M1 macrophages within the joint cavity, the research team utilized the AniView Multimodal In Vivo Imaging System from Guangzhou Biolight Biotechnology Co., Ltd. to evaluate their biosafety distribution in major organs.
The research team prepared FA-Y8 NPs through a nanoprecipitation method by assembling the photothermal agent Y8 with folic acid (FA)-conjugated materials. Cellular experiments demonstrated that the nanoparticles exhibited excellent active targeting ability due to the high expression of folate receptors on the surface of M1 macrophages. Mice were first treated with complete Freund’s adjuvant (CFA) to establish a TMJOA mouse model.
Experiments using AniView
To clarify the in vivo metabolism, clearance, and tissue-specific accumulation of the nanoparticles, nanoparticles labeled with Rhodamine B fluorescent dye were injected into mice. At 12, 24, and 72 hours after injection, fluorescence imaging of the maxillofacial region ROI (region of interest) was performed using the AniView Multimodal In Vivo Imaging System. At 48 hours after injection, mice were sacrificed, and major organs including the liver, heart, spleen, lungs, kidneys, and small intestine were collected for ex vivo fluorescence imaging to evaluate nanoparticle biodistribution in non-target organs.
In vivo imaging showed that the nanoparticles were primarily enriched around the synovial tissues in the head region. Ex vivo imaging demonstrated minimal non-specific accumulation in major non-target organs, including the heart, liver, spleen, lungs, and kidneys. The nanoparticles were also eliminated through the digestive tract, indicating excellent joint lesion-targeting capability and favorable biosafety of this nanoplatform.

DOI:org/10.1186/s12951-026-04258-9