Self-assembled nanospheres mediate phototherapy and deliver CpG oligodeoxynucleotides to enhance cancer immunotherapy of breast cancer and melanoma

Abstract

In the tumor microenvironment (TME) in certain cancer patients, the lack of tumor-associated antigens (TAAs) and low antigen presentation ability of antigen-presenting cells (APCs) limit the systemic immune effect of immune checkpoint blockade (ICB) therapy, which fails to elicit a persistent immune response. In this study, we used an important immune adjuvant (CpG ODN) and a photosensitizer (ICG) with 808 nm laser irradiation to trigger photodynamic and photothermal responses to synthesize intertwining DNA-photosensitizer nanosphere (iDP-NS) that can resolve the aforementioned shortcomings of current therapies and, together with programmed cell death-ligand 1 (PD-L1) treatment, convert uninflamed “cold” tumors into “hot” tumors. Hybrid nanosphere-mediated dual-modality photothermal/photodynamic therapy can be used to release TAAs and deliver immunostimulatory CpG ODNs to dendritic cells. In this approach, enhanced antigen presentation and immune checkpoint blockade therapy synergistically reinitiate toxic T cell activity and amplify immune effects, which can produce a powerful immune response and eliminate tumors in breast cancer and melanoma animal models. Notably, we proved that iDP-NSs mediated photo-immune response combined with ICB therapy can effectively trigger long immune memory to inhibit tumor recurrence and metastasis in 4T1 postoperative model.