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Clinicians recognize photodynamic immunotherapy for tumors as a promising treatment strategy. However, the immunosuppressive tumor microenvironment (TME) often limits its efficacy. Specifically, M2-like tumor-associated macrophages (TAMs) create a protective barrier around malignant cells. To address this, researchers developed an acid-responsive, mannose-functionalized nanoplatform called FI@PMD. M2-like macrophages selectively internalize this platform via mannose-receptor-mediated recognition. Consequently, this approach enables precise targeting within the TME.
Once the nanoplatform encounters acidic conditions, it undergoes structural dissociation. This process releases a near-infrared photosensitizer (FBC) and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). These components work in tandem to stimulate the immune system. Furthermore, the targeted delivery minimizes off-target effects in healthy tissues.
Upon light irradiation, the released FBC generates reactive oxygen species (ROS). These molecules trigger the polarization of TAMs from the M2 phenotype to the pro-inflammatory M1 phenotype. This transition remodels the TME and promotes an active anti-tumor response. In vivo experiments demonstrated that FI@PMD increased CD8+ cytotoxic T cell infiltration to 2.85-fold of the control group. Simultaneously, the proportion of regulatory T cells decreased. Therefore, this TAM-targeted strategy provides a powerful way to enhance photodynamic immunotherapy for tumors.
The nanoplatform features mannose functionalization, allowing it to be selectively internalized by M2-like tumor-associated macrophages through mannose-receptor-mediated recognition.
Repolarizing macrophages from the M2 to the M1 phenotype helps remodel the immunosuppressive tumor microenvironment, leading to significantly increased infiltration of cancer-killing CD8+ T cells.
Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a substitute for professional healthcare. Refer to the latest local and national guidelines for clinical practice.
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