Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 31, Pages 34667-34677Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c09489
Keywords
nanoreactor; palladium catalysis; prodrug; multisynergistic therapy; in situ activation
Funding
- National Natural Science Foundation of China [21977024, 21601046, 31971304]
- Natural Science Foundation of Hebei Province [B2018201185, B2018201221, B2018201157]
- Key Projects of Education Department of Hebei Province [ZD2018036]
- Advanced Talents Incubation Program of the Hebei University [801260201020]
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Efficient drug delivery into tumor cells while bypassing many biological barriers is still a challenge for cancer therapy. By taking advantage of the palladium (Pd)-mediated in situ activation of a prodrug and the glucose oxidase (GOD)-based beta-D-glucose oxidation reaction, we developed a multisynergistic cancer therapeutic platform that combined doxorubicin (DOX)-induced chemotherapy with GOD-mediated cancer-orchestrated oxidation therapy and cancer starvation therapy. In the present work, we first synthesized DOX prodrugs (pDOXs) and temporarily assembled them with beta-cyclodextrins to reduce their toxic side effects. Then, a nanoreactor was constructed by synthesizing Pd-0 nanoparticles in situ within the pores of mesoporous silica nanoparticles for the conversion of pDOX into the active anticancer drug. Furthermore, GOD was introduced to decrease the pH of the tumor microenvironment and induce cancer-orchestrated oxidation/starvation therapy by catalyzing beta-D-glucose oxidation to form hydrogen peroxide (H2O2) and gluconic acid. Our study provides a new strategy that employs a cascade chemical reaction to achieve combined orchestrated oxidation/starvation/chemotherapy for the synergistic killing of cancer cells and the suppression of tumor growth.
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