Immunogenic cell death(ICD)has gained increasing attention due to its capacity to trigger anticancer immunity.Herein,we report a series of fabricated cationic spherical polypeptides(CSPs)designated CSP-0 to CSP-57,wit...Immunogenic cell death(ICD)has gained increasing attention due to its capacity to trigger anticancer immunity.Herein,we report a series of fabricated cationic spherical polypeptides(CSPs)designated CSP-0 to CSP-57,with oncolytic activity and ICDinducing ability.CSP-57 exerted the optimal broadspectrum and tumor-cell-selective cytotoxicity by disrupting cell membranes and inducing cell necrosis.Moreover,CSP-57 damaged mitochondrial membranes,thereby elevating intracellular levels of reactive oxygen species,leading to robust ICD of tumor cells featured by multiple damage-associated molecular patterns,including calreticulin,high-mobility group box 1,and adenosine triphosphate.In vivo anticancer activity determination results suggested that CSP-57 significantly delayed B16F10 tumor growth in mice by direct oncolysis and subsequent induction of ICD.The immunotherapeutic efficacy of CSP-57 was characterized by elevated ratios of cytotoxic T cells in tumors and spleens.Briefly,this work indicates that CSPs represent a promising strategy for oncolytic immunotherapy.展开更多
基金the financial support from the National Key Research and Development Program of China(grant no.2022YFB3804600)the National Natural Science Foundation of China(grant nos.52222307,52173145,and 51833010)+2 种基金the Jilin Provincial Science and Technology Development Program,China(grant no.20220402047GH)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CASgrant no.2022226).
文摘Immunogenic cell death(ICD)has gained increasing attention due to its capacity to trigger anticancer immunity.Herein,we report a series of fabricated cationic spherical polypeptides(CSPs)designated CSP-0 to CSP-57,with oncolytic activity and ICDinducing ability.CSP-57 exerted the optimal broadspectrum and tumor-cell-selective cytotoxicity by disrupting cell membranes and inducing cell necrosis.Moreover,CSP-57 damaged mitochondrial membranes,thereby elevating intracellular levels of reactive oxygen species,leading to robust ICD of tumor cells featured by multiple damage-associated molecular patterns,including calreticulin,high-mobility group box 1,and adenosine triphosphate.In vivo anticancer activity determination results suggested that CSP-57 significantly delayed B16F10 tumor growth in mice by direct oncolysis and subsequent induction of ICD.The immunotherapeutic efficacy of CSP-57 was characterized by elevated ratios of cytotoxic T cells in tumors and spleens.Briefly,this work indicates that CSPs represent a promising strategy for oncolytic immunotherapy.
