PEG-PLGA nanoparticles as a dual ETAR and ETBR antagonist delivery platform to promote tumor microenvironment remodeling
발표자
()
초록
내용
Immune checkpoint therapy (ICT) induces tumor cell death by activating the effector function of antitumor T cells. However, tumor cells suppress cytotoxic T lymphocytes (CTLs)-mediated immune responses through immune evasion mechanisms, such as altering the tumor microenvironment (TME), resulting in low response rates in a significant proportion of patients (>70%). We designed PEG-PLGA nanoparticles (EA-NPs) to overcome this limitation as a dual ETAR and ETBR antagonist delivery platform. EA-NPs were fabricated to ~100 nm in size via nanoprecipitation and efficiently accumulated in tumor tissue via passive targeting. The accumulated EA-NPs inactivated cancer-associated fibroblasts and induced infiltration of CTLs, indicating that EA-NPs can improve immunosuppressive TME. These results suggest that the combination therapy of EA-NPs and αPD-1 is an innovative way to significantly enhance the antitumor immune response and anti-metastatic effect against immune exclusion tumors.