Moon, Yujeong Shim, Man Kyu Choi, Jiwoong Yang, Suah Kim, Jinseong Yun, Wan Su Cho, Hanhee Park, Jung Yeon Kim, Yongju Seong, Joon-Kyung Kim, Kwangmeyung 2024-01-19T12:03:27Z 2024-01-19T12:03:27Z 2022-04-05 2022-05 1838-7640 https://pubs.kist.re.kr/handle/201004/115258 Rationale: Cancer immunotherapy combining immune checkpoint blockade (ICB) with chemotherapeutic drugs has provided significant clinical advances. However, such combination therapeutic regimen has suffered from severe toxicity of both drugs and low response rate of patients. In this study, we propose anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs) to overcome these obstacles of current cancer immunotherapy. Methods: The functional peptide, consisted of anti-PD-L1 peptide and cathepsin B-specific cleavable peptide, is conjugated to a doxorubicin (DOX), resulting in prodrug nanoparticles of PD-NPs via intermolecular interactions. The antitumor efficacy and immune responses with minimal side effects by PD-NPs combining PD-L1 blockade and ICD are evaluated in breast tumor models. Results: The PD-NPs are taken up by PD-L1 receptor-mediated endocytosis and then induce ICD in cancer cells by DOX release. Concurrently, PD-L1 blockade by PD-NPs disrupt the immune-suppressing pathway of cancer cells, resulting in proliferation and reinvigoration of T lymphocytes. In tumor models, PD-NPs accumulate within tumor tissues via enhanced permeability and retention (EPR) effect and induce immune-responsive tumors by recruiting a large amount of immune cells. Conclusions: Collectively, targeted tumor delivery of anti-PD-L1 peptide and DOX via PD-NPs inhibit tumor with minimal side effects. English IVYSPRING INT PUBL Anti-PD-L1 peptide-conjugated prodrug nanoparticles for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death Article 10.7150/thno.69119 1 THERANOSTICS, v.12, no.5, pp.1999 - 2014 THERANOSTICS 12 5 1999 2014 N scie scopus 000761236700004 2-s2.0-85124599283 Medicine, Research & Experimental Research & Experimental Medicine Article DRUG-DELIVERY SYSTEMS ANTAGONIST cancer immunotherapy immune checkpoint blockade prodrug nanoparticle drug delivery antitumor immune response