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Targeted anticancer prodrug with mesoporous silica nanoparticles as vehicles.
MedLine Citation:
PMID:  22019849     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A targeted anticancer prodrug system was fabricated with 180 nm mesoporous silica nanoparticles (MSNs) as carriers. The anticancer drug doxorubicin (DOX) was conjugated to the particles through an acid-sensitive carboxylic hydrazone linker which is cleavable under acidic conditions. Moreover, folic acid (FA) was covalently conjugated to the particle surface as the targeting ligand for folate receptors (FRs) overexpressed in some cancer cells. The in vitro release profiles of DOX from the MSN-based prodrug systems showed a strong dependence on the environmental pH values. The fluorescent dye FITC was incorporated in the MSNs so as to trace the cellular uptake on a fluorescence microscope. Cellular uptakes by HeLa, A549 and L929 cell lines were tested for FA-conjugated MSNs and plain MSNs respectively, and a much more efficient uptake by FR-positive cancer cells (HeLa) can be achieved by conjugation of folic acid onto the particles because of the folate-receptor-mediated endocytosis. The cytotoxicities for the FA-conjugated MSN prodrug, the plain MSN prodrug and free DOX against three cell lines were determined, and the result indicates that the FA-conjugated MSN prodrug exhibits higher cytotoxicity to FR-positive cells, and reduced cytotoxicity to FR-negative cells. Thus, with 180 nm MSNs as the carriers for the prodrug system, good drug loading, selective targeting and sustained release of drug molecules within targeted cancer cells can be realized. This study may provide useful insights for designing and improving the applicability of MSNs in targeted anticancer prodrug systems.
Authors:
Jianquan Fan; Gang Fang; Xiaodan Wang; Fang Zeng; Yufei Xiang; Shuizhu Wu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-21
Journal Detail:
Title:  Nanotechnology     Volume:  22     ISSN:  1361-6528     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101241272     Medline TA:  Nanotechnology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  455102     Citation Subset:  -    
Affiliation:
College of Materials Science & Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, People's Republic of China.
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