Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 39, Pages 33070-33077Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b13393
Keywords
zeolitic imidazole framework-8; mesoporous silica nanoparticles; drug delivery platform; interfering RNA; multiple drug resistance
Funding
- National Natural Science Foundation of China [21525522, 21705039, 61361002]
- National Postdoctoral Program for Innovative Talents [BX201600049]
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Multiple drug resistance is a persistent obstacle for efficient chemotherapy of cancer. Herein, we report a novel drug delivery platform. A zeolitic imidazole framework-8 (ZIF-8) film with a few nanometer thickness was in situ synthesized on the surface of carboxylated mesoporous silica (MSN-COOH) nano-particles (NPs) for pore blocking and efficient loading of small interfering RNAs to fabricate a pH-responsive drug delivery system. The ZIF-8 film could convert the charge of MSN-COOH from negative to positive for efficient loading of siRNA via electrostatic interactions and protect siRNA from nuclease degradation. The positively charged ZIF-8 film facilitates cellular uptake and endolysosome escape of the NPs. In addition, the ultrathin ZIF-8 film can decompose in the acidic endo-lysosome and trigger the intracellular release of siRNAs and chemotherapeutic drugs, leading to a significantly enhanced chemotherapeutic efficacy for multidrug-resistant cancer cells including MCF-7/ADR and SKOV-3/ADR cells as demonstrated by the confocal laser scanning microscopy image, cell viability assay, Annexin V&PI staining, and flow cytometry. This approach provides a promising strategy for pH-triggered, stimuli-responsive delivery of nucleic acid drugs and chemotherapeutic agents with remarkably enhanced chemotherapeutic efficacy.
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