Research Article: Precision USPIO-PEG-SLex Nanotheranostic Agent Targeted Photothermal Therapy for Enhanced Anti-PD-L Immunotherapy to Treat Immunotherapy Resistance

Abstract:
According to data estimated by GLOBOCAN in , cancer remains one of the leading causes of death globally. Primary approaches for managing cancer encompass a range of strategies, such as surgical interventions to remove tumors, the administration of chemotherapy to attack cancer cells, utilizing radiation therapy to target and eliminate cancerous tissues, employing targeted therapy to specifically target cancer cells, utilizing hormone therapy to control hormone-driven cancers, and employing photodynamic therapy to produce reactive oxygen species (ROS) for killing cancer cells, etc.– However, due to the complexity of tumors and potential adverse effects such as resistance in radiation therapy and systemic toxicity induced by chemotherapy, traditional treatment strategies have some limitations in achieving the desired therapeutic outcomes. Recently, immune checkpoint blockade (ICB) has emerged as a promising approach in immunotherapy for a range of advanced solid tumors, including cases insensitive to platinum-based drug chemotherapy and those experiencing recurrence or metastasis. Programmed Death-Ligand (PD-L) is present on the surface of tumor cells and is an immune inhibitory molecule that suppresses T-cell activation when binding to the programmed cell death receptor (PD-) on T lymphocytes. Monoclonal antibodies (mAb) targeting PD-L have the ability to block the interaction between PD-L and its receptor PD-, which helps alleviate the inhibition of T lymphocytes and ultimately restores the immune response against malignant cells. The US Food and Drug Administration (FDA) has approved PD-L-targeting monoclonal antibodies for the treatment of various cancer types,, and ongoing clinical trials continue to explore the therapeutic potential of PD-L-targeting antibodies. However, over % of individuals with anti-PD-/PD-L immunotherapy experiences resistance, and some face disease progression when receiving anti-PD-/PD-L monotherapy.– The immunotherapy resistance may be caused by these factors: some tumor cells with relatively few gene mutations are not easily recognized by immune cells, and some tumor microenvironments are not suitable for immune cells to infiltrate or survive. Therefore, the original immune cells in such tumors are too few, and the activation effect of PD-/L inhibitors is limited. Furthermore, the more PD-L expressed by the tumor itself, the better the anti-tumor effect of PD-/L inhibitors. Due to the significant limitations of current anti-PD-/PD-L therapies, which hinder the achievement of desired outcomes, there is an urgent to explore methods that can effectively enhance the efficacy of anti-PD-/PD-L treatments.–

Introduction:
According to data estimated by GLOBOCAN in , cancer remains one of the leading causes of death globally. Primary approaches for managing cancer encompass a range of strategies, such as surgical interventions to remove tumors, the administration of chemotherapy to attack cancer cells, utilizing radiation therapy to target and eliminate cancerous tissues, employing targeted therapy to specifically target cancer cells, utilizing hormone therapy to control hormone-driven cancers, and employing photodynamic therapy to…

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