Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 33, Pages 29490-29497Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b07390
Keywords
cancer; artemisinin; mesoporous silica; nanomedicine; reactive oxygen species
Funding
- National Natural Science Foundation of China [21775166]
- Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province [BK20180026]
- Double First-Class University Project [CPU2018GF06, CPU2018GY32]
- Six Talent Peaks Project in Jiangsu Province
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Though abundant researches report that artemisinin could inhibit cancer cell growth via generating toxic reactive oxygen species (ROS), the therapeutic efficiency of artemisinin for cancer treatment is still limited owing to the insufficient intracellular ferrous ion and defensive effect of intracellular glutathione. Herein, we report a cathepsin B-controllable smart nanomedicine based on the structural and pharmacodynamic characteristics of artemisinin, which employed transferrin-peptide-modified mesoporous silica to codeliver artemisinin and buthionine-sulfoximine, a glutathione scavenger, into cancer cells. As a gatekeeper, the transferrin-peptide can not only target the cancer cells but also supply the extra ferrous iron to catalyze artemisinin to produce excessive ROS to kill cancer cells efficiently. Once the designed nanomedicine attack into lysosome of tumor cells, the cargos of nanomedicine can be released in the presence of cathepsin B to immediately activate self-amplification of oxidative stress by simultaneously elevating the levels of ROS and weakening the levels of glutathione. We anticipate that this rational design strategy provides innovative opportunities for artemisinin in the clinical application of cancer.
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