Targeted Delivery of siRNA‐Generating DNA Nanocassettes Using Multifunctional Nanoparticles

Cho, Young-Seok; Lee, Gee Young; Sajja, Hari Krishna; Qian, Weiping; Cao, Zehong; He, Weiling; Karna, Prasanthi; Chen, Xiaoyuan; Mao, Hui; Wang, Y. Andrew; Yang, Lily

doi:10.1002/smll.201201973

Cited by 30 publications

(26 citation statements)

References 47 publications

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“…Other nanosystems for targeted siRNA/shRNA delivery include a multifunctional nanoparticulate platform combining a luciferase imaging capability with an uPAR (urokinase plasminogen activator receptor)-mediated delivery of survivin siRNA-generating DNA nanocassette [87]. This system contained an amphiphilic polymer-coated nanoparticle (NP) core, conjugated with DNA nanocassettes that consisted of a U6 promoter and shRNA gene.…”

Section: Targeted Delivery Of Survivin Inhibitorsmentioning

confidence: 99%

Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

Wang

Chan

et al. 2016

Journal of Controlled Release

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Section: Targeted Delivery Of Survivin Inhibitorsmentioning

confidence: 99%

Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

Wang

Chan

et al. 2016

Journal of Controlled Release

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“…Delivery of survivin siRNA expressing nanocassettes into tumor cells has been demonstrated to effectively induce apoptotic cell death and sensitizes cells to gemcitabine-based chemotherapy [106]. …”

Section: Iron Oxide Nanoparticles For Combination Therapymentioning

confidence: 99%

Hybrid nanoparticles for combination therapy of cancer

Lin

2015

Journal of Controlled Release

121

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Nanoparticle anticancer drug delivery enhances therapeutic efficacies and reduces side effects by improving pharmacokinetics and biodistributions of the drug payloads in animal models. Despite promising preclinical efficacy results, monotherapy nanomedicines have failed to produce enhanced response rates over conventional chemotherapy in human clinical trials. The discrepancy between preclinical data and clinical outcomes is believed to result from the less pronounced enhanced permeability and retention (EPR) effect in and the heterogeneity of human tumors as well as the intrinsic/acquired drug resistance to monotherapy over the treatment course. To address these issues, recent efforts have been devoted to developing nanocarriers that can efficiently deliver multiple therapeutics with controlled release properties and increased tumor deposition. In ideal scenarios, the drug or therapeutic modality combinations have different mechanisms of action to afford synergistic effects. In this review, we summarize recent progress in designing hybrid nanoparticles for the co-delivery of combination therapies, including multiple chemotherapeutics, chemotherapeutics and biologics, chemotherapeutics and photodynamic therapy, and chemotherapeutics and radiotherapy. The in vitro and in vivo anticancer effects are also discussed.

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“…Bcl-2 is responsible for the activation of cellular anti- apoptotic defense [23]. Survivin has a functional role in caspase inhibition to lead to negative regulation of apoptosis, and is upregulated in most human tumors, making it a potential target for cancer treatment [17, 24]. We hypothesized that delivering pooled siRNAs, including siP-gp, siBcl-2, and sisurvivin, targeting different molecular signaling pathways would be an effective approach to overcoming drug resistance in cancers.…”

Section: Introductionmentioning

confidence: 99%

Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer

2015

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Resistance to the chemotherapeutic agent cisplatin is a major limitation for the successful treatment of many cancers. Development of novel strategies to overcome intrinsic and acquired resistance to chemotherapy is of critical importance to effective treatment of ovarian cancer and other types of cancers. We have sought to re-sensitize resistant ovarian cancer cells to chemotherapy by co-delivering chemotherapeutics and pooled siRNAs targeting multi-drug resistance (MDR) genes using self-assembled nanoscale coordination polymers (NCPs). In this work, NCP-1 particles with trigger release properties were first constructed by linking cisplatin prodrug-based bisphosphonate bridging ligands with Zn2+ metal-connecting points and then coated with a cationic lipid layer, followed by the adsorption of pooled siRNAs targeting three MDR genes including survivin, Bcl-2, and P-glycoprotein via electrostatic interactions. The resulting NCP-1/siRNA particles promoted cellular uptake of cisplatin and siRNA and enabled efficient endosomal escape in cisplatin-resistant ovarian cancer cells. By down-regulating the expression of MDR genes, NCP-1/siRNAs enhanced the chemotherapeutic efficacy as indicated by cell viability assay, DNA ladder, and flow cytometry. Local administration of NCP-1/siRNAs effectively reduced tumor sizes of cisplatin-resistant SKOV-3 subcutaneous xenografts. This work shows that the NCP-1/siRNA platform holds great promise in enhancing chemotherapeutic efficacy for the effective treatment of drug-resistant cancers.

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Targeted Delivery of siRNA‐Generating DNA Nanocassettes Using Multifunctional Nanoparticles

Cited by 30 publications

References 47 publications

Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

Nanoparticle-mediated inhibition of survivin to overcome drug resistance in cancer therapy

Hybrid nanoparticles for combination therapy of cancer

Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer

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