期刊
JOURNAL OF CONTROLLED RELEASE
卷 350, 期 -, 页码 922-932出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.09.013
关键词
Oxaliplatin prodrugs; Metformin; Colorectal cancer; Immune checkpoint blockade therapy
资金
- National Natural Science Foundation of China [22077093, 52032008]
- Ministry of Science and Technology (MOST) of China [2021YFF0701800]
- Natural Science Foundation of Jiangsu Province [BK20220110]
- Jiangsu Social Development Project [BE2019658]
- Suzhou Key Laboratory of Nanotechnology and Biomedicine
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- 111 Program from the Ministry of Education of China
- National Clinical Research Center for Hematologic Diseases
- First Affiliated Hospital of Soochow University [2020WSC07]
- Key R & D Program of Jiangsu Province [BE2021644]
- Scientific Research Project of the Health Commission of Nantong [QA2021029]
A liposomal nanomedicine that modulates the tumor microenvironment has been developed to enhance cancer immunotherapy. By encapsulating metformin and an oxaliplatin prodrug in liposomes, this nanomedicine reduces tumor hypoxia and induces immunogenic cell death, effectively suppressing tumor growth and reversing immunosuppression.
Tumor hypoxia is confirmed to be associated with the formation of tumor immunosuppression, a general feature of solid tumors, and thus attenuates the effectiveness of various cancer therapies in clinic. We herein develop a tumor microenvironment (TME) modulating liposomal nanomedicine by encapsulating metformin with amphi-philic oxaliplatin prodrug constructed liposomes to potentiate cancer immunotherapy. While metformin could regulate metabolisms of tumor cells to reduce their oxygen consumption and relieve tumor hypoxia, oxaliplatin is a chemotherapy drug that induces immunogenic cell death (ICD). The obtained met-oxa(IV)-liposome upon intravenous injection effectively attenuates tumor hypoxia and induce ICD of cancer cells, thereby collectively suppresses the growth of murine colorectal tumors by eliciting potent antitumor immunity and reversing the immunosuppressive TME. As the result, the treatment with met-oxa(IV)-liposome effectively potentiates the immune checkpoint blockade (ICB) therapy against murine colorectal tumors. This liposomal nanomedicine is highlighted to be a TME modulating liposomal nanomedicine with high potency in suppressing tumor growth, particularly promising in synergizing with ICB therapy by boosting antitumor immune responses.
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