Multifunctional Nanoparticles-Mediated PTT/PDT Synergistic Immune Activation and Antitumor Activity Combined with Anti-PD-L1 Immunotherapy for Breast Cancer Treatment

Introduction: Photoimmunotherapy is a breakthrough treatment for malignant tumors. Its uniqueness is that it uses antibody mediated targeted delivery to achieve high tumor specificity and uses laser-activated biophysical mechanism to accurately induce the rapid death of cancer cells and avoid damaging the surrounding normal tissues. Methods: In this paper, an iron-based micelle was designed to encapsulate the photothermal agent indocyanine green (ICG) and a cyclic tripeptide of arginine-glycine-aspartic acid (cRGD) as targeted multifunctional [email protected] nanoparticles for combined photothermal/photodynamic/immune therapy of breast cancer. Results: The experimental results show that [email protected] nanoparticles have good biocompatibility and photothermal conversion ability. Photothermal therapy (PTT) and photodynamic therapy (PDT) based on [email protected] can not only inhibit the proliferation, invasion and migration of tumor cells, but also directly kill tumor cells by inducing apoptosis or necrosis. Dual-mode fluorescence light (FL) and magnetic resonance imaging (MRI) imaging in mice confirmed the selective accumulation at tumor sites and imaging ability of [email protected] PTT/PDT combined with Anti-PD-L1 immunotherapy based on [email protected] mediated the immunogenic cell death (ICD) of tumor cells by regulating the expression of immune-related indicators and activated the body’s immune response mechanism, which enhanced the immunotherapy effect of immune checkpoint block (ICB). PTT/PDT combined with Anti-PD-L1 therapy not only prevented the progression of the primary tumor but also inhibited the distant metastasis of the tumor. Discussion: This study explores the biomedical application of PTT/PDT combined with Anti-PD-L1 based on [email protected] nanomaterials for breast cancer treatment and demonstrates the potential of [email protected] as a multifunctional therapeutic platform for future cancer therapy. Keywords: photodynamic therapy, photothermal therapy, immune checkpoint blocking, immune enhancement effect