| Folate-PEG-Appended Dendrimer Conjugate with α-Cyclodextrin as a Novel Cancer Cell-Selective siRNA Delivery Carrier. | |
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MedLine Citation:
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PMID: 22873579 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We previously reported that of the various polyamidoamine (PAMAM) STARBURST dendrimer (generation 3, G3) (dendrimer) conjugates with cyclodextrins (CyDs), the dendrimer (G3) conjugate with α-CyD having an average degree of substitution of 2.4 (α-CDE (G3)) has the greatest potential for a novel carrier for siRNA in vitro and in vivo. To improve the siRNA transfer activity and the lack of target specificity of α-CDE (G3), we prepared folate-polyethylene glycol (PEG)-appended α-CDEs (G3) (Fol-PαCs) with various degrees of substitution of folate (DSF) and evaluated their siRNA transfer activity to folate receptor (FR)-overexpressing cancer cells in vitro and in vivo. Of the three Fol-PαCs (G3, DSF 2, 4 and 7), Fol-PαC (G3, DSF 4) had the highest siRNA transfer activity in KB cells (FR-positive). Fol-PαC (G3, DSF 4) was endocytosed into KB cells through FR. No cytotoxicity of the siRNA complex with Fol-PαC (G3, DSF 4) was observed in KB cells (FR-positive) or A549 cells (FR-negative) up to the charge ratio of 100/1 (carrier/siRNA). In addition, the siRNA complex with Fol-PαC (G3, DSF 4) showed neither interferon response nor inflammatory response. Importantly, the siRNA complex with Fol-PαC (G3, DSF 4) tended to show the in vivo RNAi effects after intratumoral injection and intravenous injection in tumor cells-bearing mice. The FITC-labeled siRNA and TRITC-labeled Fol-PαC (G3, DSF 4) were actually accumulated in tumor tissues after intravenous injection in the mice. In conclusion, the present results suggest that Fol-PαC (G3, DSF 4) could potentially be used as a FR-overexpressing cancer cell-selective siRNA delivery carrier in vitro and in vivo. |
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Authors:
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Hidetoshi Arima; Ayumi Yoshimatsu; Haruna Ikeda; Ayumu Ohyama; Keiichi Motoyama; Taishi Higashi; Akira Tsuchiya; Takuro Niidome; Yoshiki Katayama; Kenjiro Hattori; Tomoko Takeuchi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-9 |
Journal Detail:
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Title: Molecular pharmaceutics Volume: - ISSN: 1543-8392 ISO Abbreviation: Mol. Pharm. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University , 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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