Sustained Small Interfering RNA Delivery by Mesoporous Silicon Particles
Takemi TanakaAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoLingegowda S. MangalaDepartment of Surgery and The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoPablo E. Vivas‐MejíaAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoRené Nieves-AliceaAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoAman P. MannAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoEdna MoraAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoHee‐Dong HanAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoMian M.K. ShahzadAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoXuewu LiuAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoRohan BhavaneAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoJianhua GuAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoJean R. FakhouryAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoCiro ChiappiniAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoChunhua LüAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoKoji MatsuoAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoBiana GodinAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoRebecca L. StoneAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoAlpa M. NickAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoGabriel Lopez‐BeresteinAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoAnil K. SoodAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto RicoMauro FerrariAuthors' Affiliations: 1Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center at Houston; Departments of 2Gynecologic Oncology, 3Cancer Biology, 4Experimental Therapeutics, and 5Surgical Oncology, and 6Center for RNA Interference and Non-Coding RNA, University of Texas M.D. Anderson Cancer Center; 7Department of Bioengineering, Rice University; and 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; 9Department of Biomedical Engineering, University of Texas Austin, Austin, Texas; and 10Department of Surgery and 11The University of Puerto Rico Comprehensive Cancer Center, San Juan, Puerto Rico
2010en
ABI
Annotatsiya
RNA interference (RNAi) is a powerful approach for silencing genes associated with a variety of pathologic conditions; however, in vivo RNAi delivery has remained a major challenge due to lack of safe, efficient, and sustained systemic delivery. Here, we report on a novel approach to overcome these limitations using a multistage vector composed of mesoporous silicon particles (stage 1 microparticles, S1MP) loaded with neutral nanoliposomes (dioleoyl phosphatidylcholine, DOPC) containing small interfering RNA (siRNA) targeted against the EphA2 oncoprotein, which is overexpressed in most cancers, including ovarian. Our delivery methods resulted in sustained EphA2 gene silencing for at least 3 weeks in two independent orthotopic mouse models of ovarian cancer following a single i.v. administration of S1MP loaded with EphA2-siRNA-DOPC. Furthermore, a single administration of S1MP loaded with-EphA2-siRNA-DOPC substantially reduced tumor burden, angiogenesis, and cell proliferation compared with a noncoding control siRNA alone (SKOV3ip1, 54%; HeyA8, 57%), with no significant changes in serum chemistries or in proinflammatory cytokines. In summary, we have provided the first in vivo therapeutic validation of a novel, multistage siRNA delivery system for sustained gene silencing with broad applicability to pathologies beyond ovarian neoplasms.
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