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Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxia-inducible factor 1 alpha enhances the efficacy of chemotherapy in drug-resistant tumor.
Clin Cancer Res. 2008 Jun 01; 14(11):3607-16.CC

Abstract

PURPOSE

To enhance the efficacy of cancer treatment, we propose a complex approach: simultaneous delivery to the tumor of a chemotherapeutic agent and a suppressor of hypoxia-inducible factor 1 alpha (HIF1A).

EXPERIMENTAL DESIGN

The novel complex liposomal drug delivery system was developed and evaluated in vitro and in vivo on nude mice bearing xenografts of multidrug-resistant human ovarian carcinoma. The proposed novel complex drug delivery system consists of liposomes as a nanocarrier, a traditional anticancer drug (doxorubicin) as a cell death inducer, and antisense oligonucleotides targeted to HIF1A mRNA as a suppressor of cellular resistance and angiogenesis.

RESULTS

The system effectively delivers active ingredients into tumor cells, multiplies the cell death signal initiated by doxorubicin, and inhibits cellular defensive mechanisms and angiogenesis by down-regulating BCL2, HSP90, and vascular endothelial growth factor proteins. This, in turn, activates caspases, promotes apoptosis, necrosis, and tumor shrinkage. The proposed novel complex multipronged approach enhances the efficiency of chemotherapy.

CONCLUSIONS

The proposed combination therapy prevents the development of resistance in cancer cells, and thus, increases the efficacy of chemotherapy to an extent that cannot be achieved by individual components applied separately. It could form the foundation for a novel type of cancer therapy based on simultaneous delivery of an anticancer drug and a suppressor of HIF1A.

Authors+Show Affiliations

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18519795

Citation

Wang, Yang, et al. "Nonviral Nanoscale-based Delivery of Antisense Oligonucleotides Targeted to Hypoxia-inducible Factor 1 Alpha Enhances the Efficacy of Chemotherapy in Drug-resistant Tumor." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 14, no. 11, 2008, pp. 3607-16.
Wang Y, Saad M, Pakunlu RI, et al. Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxia-inducible factor 1 alpha enhances the efficacy of chemotherapy in drug-resistant tumor. Clin Cancer Res. 2008;14(11):3607-16.
Wang, Y., Saad, M., Pakunlu, R. I., Khandare, J. J., Garbuzenko, O. B., Vetcher, A. A., Soldatenkov, V. A., Pozharov, V. P., & Minko, T. (2008). Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxia-inducible factor 1 alpha enhances the efficacy of chemotherapy in drug-resistant tumor. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 14(11), 3607-16. https://doi.org/10.1158/1078-0432.CCR-07-2020
Wang Y, et al. Nonviral Nanoscale-based Delivery of Antisense Oligonucleotides Targeted to Hypoxia-inducible Factor 1 Alpha Enhances the Efficacy of Chemotherapy in Drug-resistant Tumor. Clin Cancer Res. 2008 Jun 1;14(11):3607-16. PubMed PMID: 18519795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxia-inducible factor 1 alpha enhances the efficacy of chemotherapy in drug-resistant tumor. AU - Wang,Yang, AU - Saad,Maha, AU - Pakunlu,Refika I, AU - Khandare,Jayant J, AU - Garbuzenko,Olga B, AU - Vetcher,Alexandre A, AU - Soldatenkov,Viatcheslav A, AU - Pozharov,Vitaly P, AU - Minko,Tamara, PY - 2008/6/4/pubmed PY - 2008/8/30/medline PY - 2008/6/4/entrez SP - 3607 EP - 16 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 14 IS - 11 N2 - PURPOSE: To enhance the efficacy of cancer treatment, we propose a complex approach: simultaneous delivery to the tumor of a chemotherapeutic agent and a suppressor of hypoxia-inducible factor 1 alpha (HIF1A). EXPERIMENTAL DESIGN: The novel complex liposomal drug delivery system was developed and evaluated in vitro and in vivo on nude mice bearing xenografts of multidrug-resistant human ovarian carcinoma. The proposed novel complex drug delivery system consists of liposomes as a nanocarrier, a traditional anticancer drug (doxorubicin) as a cell death inducer, and antisense oligonucleotides targeted to HIF1A mRNA as a suppressor of cellular resistance and angiogenesis. RESULTS: The system effectively delivers active ingredients into tumor cells, multiplies the cell death signal initiated by doxorubicin, and inhibits cellular defensive mechanisms and angiogenesis by down-regulating BCL2, HSP90, and vascular endothelial growth factor proteins. This, in turn, activates caspases, promotes apoptosis, necrosis, and tumor shrinkage. The proposed novel complex multipronged approach enhances the efficiency of chemotherapy. CONCLUSIONS: The proposed combination therapy prevents the development of resistance in cancer cells, and thus, increases the efficacy of chemotherapy to an extent that cannot be achieved by individual components applied separately. It could form the foundation for a novel type of cancer therapy based on simultaneous delivery of an anticancer drug and a suppressor of HIF1A. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/18519795/Nonviral_nanoscale_based_delivery_of_antisense_oligonucleotides_targeted_to_hypoxia_inducible_factor_1_alpha_enhances_the_efficacy_of_chemotherapy_in_drug_resistant_tumor_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18519795 DB - PRIME DP - Unbound Medicine ER -