期刊
NANO LETTERS
卷 19, 期 11, 页码 8333-8341出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b04147
关键词
Immunogenic cell death; carfilzomib; nanocapsules; tannic acid; sustained release
类别
资金
- National Institutes of Health [R01 EB017791, R01 CA232419]
- Egyptian Government Ministry of Higher Education Missions Sector
- Indiana Clinical and Translational Sciences Institute - National Institutes of Health, National Center for Advancing Translational Sciences, Clinical, and Translational Sciences Award [UL1 TR001108]
- Purdue University Institute for Drug Discovery
A group of chemotherapeutic drugs has gained increasing interest in cancer immunotherapy due to the potential to induce immunogenic cell death (ICD). A critical challenge in using the ICD inducers in cancer immunotherapy is the immunotoxicity accompanying their antiproliferative effects. To alleviate this, a nanocapsule formulation of carfilzomib (CFZ), an ICD-inducing proteasome inhibitor, was developed using interfacial supramolecular assembly of tannic acid (TA) and iron, supplemented with albumin coating. The albumin-coated CFZ nanocapsules (CFZ-pTA-alb) attenuated CFZ release, reducing toxicity to immune cells. Moreover, due to the adhesive nature of the TA assembly, CFZ-pTA-alb served as a reservoir of damage-associated molecular patterns released from dying tumor cells to activate dendritic cells. Upon intratumoral administration, CFZ-pTA-alb prolonged tumor retention of CFZ and showed consistently greater antitumor effects than cyclodextrin-solubilized CFZ (CFZ-CD) in B16F10 and CT26 tumor models. Unlike CFZ-CD, the locally injected CFZ-pTA-alb protected or enhanced CD8(+) T cell population in tumors, helped develop splenocytes with tumor-specific interferon-gamma response, and delayed tumor development on the contralateral side in immunocompetent mice (but not in athymic nude mice), supporting that CFZ-pTA-alb contributed to activating antitumor immunity. This study demonstrates that sustained delivery of ICD inducers by TA-based nanocapsules is an effective way of translating local ICD induction to systemic antitumor immunity.
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