Exploring structure-directed immunogenic cytotoxicity of arginine-rich peptides for cytolysis-induced immunotherapy of cancer.

Autor: Huang L; Nanobiomedicine Division, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China., Li A; Nanobiomedicine Division, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China., Liu HJ; Nanobiomedicine Division, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China., Ji SS; Nanobiomedicine Division, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; Key Laboratory of Nano-Bio Interface, Chinese Academy of Sciences, Suzhou 215123, China., Fei H; Nanobiomedicine Division, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; Key Laboratory of Nano-Bio Interface, Chinese Academy of Sciences, Suzhou 215123, China. Electronic address: hfei2008@sinano.ac.cn.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Dec 15; Vol. 116, pp. 117984. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1016/j.bmc.2024.117984
Abstrakt: The same cells can die with varied immunological consequences. For the purpose of cancer therapy, stronger immunogenic death of cancer cells is considered favorable. Membrane disruptive peptides are cytotoxic agents with tunable structures capable of not just killing heterogeneous cancer cells, but also inducing immunogenic death. However, the chemo-structural principles that underlie their immunogenic cytotoxicity remain elusive. Here we investigated a series of arginine-rich amphipathic peptides with representative structures on the relationship between the mode of cell death and the immunogenic potency. Among several hydrophobic motif-appended cyclic octaarginine peptides, FC-14 was found to induce cell stress and necroptotic death, unlike apoptotic peptide RL2 and membrane-dissolving peptide RL1. Their differing abilities to release immunogenic death markers correlated well with their potential to activate innate immunity and protective vaccinal effect in a prophylactic model, with FC-14 being the most potent. FC-14 can be pre-opsonized with albumin into nanoparticles (PopAN-FC-14) using PopAN technology to improve its pharmacokinetic properties for intravenous injection. In a syngeneic mouse model of subcutaneous breast cancer, PopAN-FC-14 showed superior therapeutic effect and safety profile than the albumin formulated nanomedicine Nab-paclitaxel (Nab-PTX). Boost injections of PopAN-FC-14 significantly enhanced tumor-specific cellular and humoral immunities, acting similarly as in-situ cancer vaccine. Overall, this work demonstrates a novel focus on the immunogenic cytotoxicity of peptides and a practical approach for effective systemic therapy of cancer.
Competing Interests: Declaration of competing interest The reported compounds and the PopAN methods have been patented or under application. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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