Nanoscale metal-organic frameworks for the co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells
Open accessAbstract
Ovarian cancer is the leading cause of death among women with gynecological malignancies. Acquired resistance to chemotherapy is a major limitation for ovarian cancer treatment. We report here the first use of nanoscale metal-organic frameworks (NMOFs) for the co-delivery of cisplatin and pooled small interfering RNAs (siRNAs) to enhance therapeutic efficacy by silencing multiple drug resistance (MDR) genes and resensitizing resistant ovarian cancer cells to cisplatin treatment. UiO NMOFs with hexagonal-plate morphologies were loaded with a cisplatin prodrug and MDR gene-silencing siRNAs (Bcl-2, P-glycoprotein [P-gp], and survivin) via encapsulation and surface coordination, respectively. NMOFs protect siRNAs from nuclease degradation, enhance siRNA cellular uptake, and promote siRNA escape from endosomes to silence MDR genes in cisplatin-resistant ovarian cancer cells. Co-delivery of cisplatin and siRNAs with NMOFs led to an order of magnitude enhancement in chemotherapeutic efficacy in vitro, as indicated by cell viability assay, DNA laddering, and Annexin V staining. This work shows that NMOFs hold great promise in the co-delivery of multiple therapeutics for effective treatment of drug-resistant cancers.
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Conventional strategy is to inhibit expression or activity of drug resistance-associated genes through siRNA or chemical inhibitors.
“The conventional strategy is to inhibit the expression or activity of these genes through small interfering RNA (siRNA) or chemical inhibitors [135–137].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [135]
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- Authors
- He, C., Lu, K., Liu, D., & Lin, W.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Lin, Wenbin
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-03-26
- Volume
- 136
- Issue
- 14
- Pages
- 5181-5184
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC4210117
- OpenAlex
- W2320312730
- Cited by
- 885
- References
- 31
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 62 · 2023: 70 · 2022: 75 · 2021: 79 · 2020: 105 · 2019: 101 · 2018: 91 · 2017: 96 · 2016: 72 · 2015: 53 · 2014: 16
- FWCI
- 33.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of the American Chemical Society (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UO1-CA151455)
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Organic Frameworks: Synthesis and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- nanoscale metal-organic frameworks, cisplatin, siRNA co-delivery, ovarian cancer, drug resistance, P-glycoprotein, Bcl-2, survivin, chemosensitization, siRNA delivery, endosomal escape, nuclease protection, UiO-66
- MeSH terms
- Antineoplastic Agents, Cell Survival, Cisplatin, Female, Humans, Organometallic Compounds, Ovarian Neoplasms, Particle Size, Surface Properties, Drug Resistance, Neoplasm, RNA, Small Interfering, Nanostructures
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