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

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.