Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs
Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/97479 https://orcid.org/0000-0002-8848-7559 |
| _version_ | 1811084215988518912 |
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| author | Choi, Ki Young Silvestre, Oscar F. Huang, Xinglu Min, Kyung Hyun Howard, Gregory P. Hida, Naoki Jin, Albert J. Carvajal, Nicole Lee, Sang Wook Hong, Jong-In Chen, Xiaoyuan |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Choi, Ki Young Silvestre, Oscar F. Huang, Xinglu Min, Kyung Hyun Howard, Gregory P. Hida, Naoki Jin, Albert J. Carvajal, Nicole Lee, Sang Wook Hong, Jong-In Chen, Xiaoyuan |
| author_sort | Choi, Ki Young |
| collection | MIT |
| description | Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells. |
| first_indexed | 2024-09-23T12:47:07Z |
| format | Article |
| id | mit-1721.1/97479 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:47:07Z |
| publishDate | 2015 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/974792022-09-28T09:59:22Z Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs Choi, Ki Young Silvestre, Oscar F. Huang, Xinglu Min, Kyung Hyun Howard, Gregory P. Hida, Naoki Jin, Albert J. Carvajal, Nicole Lee, Sang Wook Hong, Jong-In Chen, Xiaoyuan Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Choi, Ki Young Jin, Albert J. Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells. National Institute for Biomedical Imaging and Bioengineering (U.S.) National Institutes of Health (U.S.) AXA Research Fund (Postdoctoral Fellowship) National Research Foundation of Korea (Postdoctoral Fellowship 2013R1A6A3A03) National Research Foundation of Korea (Grant 2009-0080734) 2015-06-19T18:44:03Z 2015-06-19T18:44:03Z 2014-04 2014-01 Article http://purl.org/eprint/type/JournalArticle 1936-0851 1936-086X http://hdl.handle.net/1721.1/97479 Choi, Ki Young, Oscar F. Silvestre, Xinglu Huang, Kyung Hyun Min, Gregory P. Howard, Naoki Hida, Albert J. Jin, et al. “Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs.” ACS Nano 8, no. 5 (May 27, 2014): 4559–4570. © 2014 American Chemical Society https://orcid.org/0000-0002-8848-7559 en_US http://dx.doi.org/10.1021/nn500085k ACS Nano Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) American Chemical Society |
| spellingShingle | Choi, Ki Young Silvestre, Oscar F. Huang, Xinglu Min, Kyung Hyun Howard, Gregory P. Hida, Naoki Jin, Albert J. Carvajal, Nicole Lee, Sang Wook Hong, Jong-In Chen, Xiaoyuan Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs |
| title | Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs |
| title_full | Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs |
| title_fullStr | Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs |
| title_full_unstemmed | Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs |
| title_short | Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs |
| title_sort | versatile rna interference nanoplatform for systemic delivery of rnas |
| url | http://hdl.handle.net/1721.1/97479 https://orcid.org/0000-0002-8848-7559 |
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