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The characteristics and performance of a multifunctional nanoassembly system for the co-delivery of docetaxel and iSur-pDNA in a mouse hepatocellular carcinoma model

Paper ID Volume ID Publish Year Pages File Format Full-Text
9916 653 2010 7 PDF Available
Title
The characteristics and performance of a multifunctional nanoassembly system for the co-delivery of docetaxel and iSur-pDNA in a mouse hepatocellular carcinoma model
Abstract

Human hepatocellular carcinoma (HCC) is one of the most causes of cancer-related death and is well known because of resistant to chemotherapeutic drug. Co-delivery of antitumor agent docetaxel and iSur-pDNA, a suppressor of metastatic and resistance-related protein survivin, was postulated to achieve synergistic/combined effect of antitumor drug and gene therapeutics. To valid this hypothesis, a folate-modified multifunctional nanoassembly (FNA) loading both docetaxel and iSur-pDNA was constructed and evaluated as a therapeutic approach for HCC. The FNAs were prepared with folate-modified lipid FA-PEG-DSPE as the target to tumor, protamine sulfate (PS) as the condenser to protect and enhance the nuclear transfer of iSur-pDNA, and DOPE-based lipid envelope as the carrier of doctaxel and PS/DNA complex to achieve their co-delivery and enhance internalization into hepatoma cells. FNAs showed the particle size about 200 nm with encapsulation efficiency >90%. Blank nanoassemblies (BNAs) loading only reporter gene revealed higher transfection efficiency with neglectable cytotoxicity compared with Lipofectamine™ 2000, which could result from enhanced cellular uptake via ligand-receptor recognition and efficient nuclear delivery mediated by PS. Cytotoxicity of FNAs against hepatocellular carcinoma cell line BEL 7402 was much higher than either docetaxel or non-docetaxel FNAs (nFNAs) loading only iSur-pDNA, and was also superior to the combined treatment with free docetaxel and nFNAs. Better antitumor efficacy of FNAs with low systemic toxicity was also observed on mouse hepatocellular carcinoma xenograft model. These results suggested that co-delivery of docetaxel and iSur-pDNA with FNAs could be a safer and more efficient strategy for the treatment of locally advanced and metastatic HCC.

Keywords
Hepatocellular carcinoma; Chemotherapy; Gene therapy; Co-delivery; Docetaxel; Survivin
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The characteristics and performance of a multifunctional nanoassembly system for the co-delivery of docetaxel and iSur-pDNA in a mouse hepatocellular carcinoma model
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 5, February 2010, Pages 916–922
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us