A combination strategy based on an Au nanorod/doxorubicin gel via mild photothermal therapy combined with antigen-capturing liposomes and anti-PD-L1 agent promote a positive shift in the cancer-immunity cycle

Abstract

The antitumor immune response involves a cascade of cancer-immunity cycles. Developing a combination therapy aimed at the cancer-immunity cycle is of great importance. In this research, we designed and tested a combined therapeutic-Au nanorod (AuNR)/doxorubicin (DOX) gel (AuNR/DOX gel)-in which the sustained release of DOX was controlled by Pluronic gel. DOX served as an immunogenic tumor cell death (ICD) inducer, triggering the production of damage-associated molecular patterns (DAMPs). Mild photothermal therapy (Mild PTT) produced by 880 nm laser-irradiated AuNRs also generated tumor-associated antigens. Maleimide-modified liposomes (L-Mals), as antigen capturing agents, promoted tumor antigen uptake by DCs. Ultimately, more CD8+ T cells and fewer regulatory T cells (Tregs) infiltrated the tumor, eliciting antitumor responses from the PD-L1 antibody. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system. STATEMENT OF SIGNIFICANCE: Developing a combination therapy for cancer-immunity cycle is of great importance due to antitumor immune response involving a cascade of cancer-immunity cycles. Cancer-immunity cycle usually includes tumor antigen release, antigen presentation, immune activation, trafficking, infiltration, specific recognition of tumor cells by T cells, and finally cancer cell killing. In this research, we designed a combination strategy based on Au nanorod/doxorubicin gel via mild photothermal therapy combined with antigen-capturing liposomes and anti-PD-L1 agent promoting a positive shift in the cancer-immunity cycle. Our results indicate that this combination strategy promotes a positive shift in the cancer-immunity cycle and holds much promise for combination strategy will lead to development of an antitumor drug delivery system.

Keywords: Antigen capture; Au nanorod/doxorubicin gel; Cancer immunity cycle; Immunogenic cell death; Immunotherapy; Mild photothermal therapy.