کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1424837 986741 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Surface-modified silica nanoparticles for tumor-targeted delivery of camptothecin and its biological evaluation
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Surface-modified silica nanoparticles for tumor-targeted delivery of camptothecin and its biological evaluation
چکیده انگلیسی

Here we report the design, synthesis and biological evaluation of surface-modified silica nanoparticles (SNP) for the delivery of camptothecin (CPT). Drug has been covalently linked to the nanoparticle through an ester bond with the 20-hydroxy moiety, in order to stabilize its lactone ring and to avoid unspecific release of the drug. The obtained material is highly stable in plasma, with low release of the cargo at physiological pH. Cell internalization and in vitro efficacy assays demonstrated that nanoparticles carrying CPT (SNP-CPT) entered cells via endocytosis and the intracellular release of the cargo induced cell death with half maximal inhibitory concentration (IC50) values and cell cycle distribution profiles similar to those observed for the naked drug. Further, in vivo biodistribution, therapeutic efficacy and biocompatibility of the SNP-CPT were evaluated in human colorectal cancer xenografts using in vivo fluorescence or bioluminescence optical imaging. In vivo tumor-accumulation and whole-body tissue distribution were carried out based on the acquisition of fluorescence emission of a fluorophore (Cy5.5) conjugated to the SNP-CPT, as well as by HPLC quantification of tissue CPT levels. The results showed that, although SNP-CPT tended to accumulate in organs of the reticulo-endothelial system, nanoparticles boost CPT concentration in tumor vs administration of the free drug. Accordingly, SNP-CPT treatment delayed the growth of subcutaneous tumors while significantly reducing the systemic toxicity associated with CPT administration. These results indicate that the SNP-CPT could be used as a robust drug delivery system for antitumoral treatments based on CPT.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 156, Issue 2, 10 December 2011, Pages 246–257
نویسندگان
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