Anti-PD-L1 Antibody Fragment Linked to Tumor-Targeting Lipid Nanoparticle Can Eliminate Cancer and Its Metastasis via Photoimmunotherapy

Abstract

Effective cancer therapy aims to treat primary tumors and metastatic and recurrent cancer. Immune checkpoint blockade-mediated immunotherapy has shown promising effects against tumors; however, its efficacy in metastatic or recurrent cancer is limited. Here, based on the advantages of nanomedicine, lipid nanoparticles (LNPs) that can target tumors are synthesized for photothermal therapy (PTT) and immunotherapy to treat primary and metastatic recurrent cancer. These LNPs, termed piLNPs, are encapsulated with indocyanine green and incorporated with the antigen (Ag)-binding fragment of the anti-PD-L1 antibody for targeting tumors and immunotherapy. Intravenously injected piLNPs in 4T1 breast tumor-bearing BALB/c mice effectively target the 4T1 tumor and are suitable for performing PTT using a near-infrared laser. Moreover, lung metastatic 4T1 tumor growth is completely prevented in mice previously cured of the 4T1 breast tumor by piLNP treatment and rechallenged with lung 4T1 metastatic cancer. Blockage of the second challenged metastatic 4T1 breast cancer by piLNP is due to the activation of Ag-specific T cells. Cytotoxic T lymphocytes from piLNP-cured mice selectively attack 4T1 breast cancer cells. Therefore, piLNP can be used as a multifunctional breast cancer treatment composition that can target tumors, treat primary tumors, and prevent metastasis and recurrence.