期刊
BIOMATERIALS
卷 280, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.121315
关键词
Nanoparticle; Iron; Artemisinin; Ferroptosis; Cancer; Immunotherapy
资金
- National Cancer Institute [1R01CA216436, 1R01CA223184]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
This study demonstrates the enhanced antitumor efficacy of DHA through co-delivery with a cholesterol derivative and an iron complex in nanoparticles. The combination treatment also improves tumor immunogenicity, making non-immunogenic colorectal tumors more susceptible to immunotherapy.
Dihydroartemisinin (DHA) has shown cytotoxicity against various tumor cells in vitro in an iron-dependent manner, but its in vivo antitumor efficacy is compromised by its rapid degradation and clearance. Here we show the induction of ferroptosis by DHA in an immunogenic fashion and the maximization of in vivo antitumor efficacy of DHA by co-delivering a cholesterol derivative of DHA (Chol-DHA) and Pyropheophorbide-iron (PyroFe) in ZnP@DHA/Pyro-Fe core-shell nanoparticles. ZnP@DHA/Pyro-Fe particles stabilize DHA against hydrolysis and prolong blood circulation of Chol-DHA and Pyro-Fe for their enhanced uptake in tumors. Co-delivery of an exogenous iron complex and DHA induces more ROS production and causes significant tumor inhibition in vivo. By increasing tumor immunogenicity, the combination of DHA and Pyro-Fe sensitizes non-immunogenic colorectal tumors to anti-PD-L1 checkpoint blockade immunotherapy. These findings suggest the potential of using nanotechnology to repurpose DHA and other drugs with excellent safety profiles for combination with immune checkpoint blockade to treat cancers.
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