Document Detail


Cell-specific delivery of polymeric nanoparticles to carbohydrate-tagging cells.
MedLine Citation:
PMID:  17883278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Carbohydrates on cell surfaces contribute a variety of communications between the cell and its environment, and they have been assumed to act as markers for cellular recognition. In this research, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer nanoparticles, which can react with specific carbohydrates of target cells, were newly prepared to serve as novel drug carriers. A water-soluble MPC polymer bearing hydrazide groups (PMBH) was synthesized by conventional radical polymerization. The MPC polymer showed amphiphilic nature and worked as an emulsifier to form nanoparticles. The nanoparticles covered with PMBH were prepared by the solvent evaporation method and exhibited monodispersity. They were approximately 200 nm in diameter and -2.0 mV in surface potential. According to a surface analysis of the nanoparticles, phosphorylcholine and hydrazide groups were observed, and the surface was fully covered with PMBH. Unnatural carbohydrates having ketone groups on human cervical carcinoma cell (HeLa) surfaces were expressed by treatment with levulinoyl mannosamine (ManLev). When the PMBH nanoparticles were in contact with the ManLev-treated HeLa cells, they accumulated in the cells. In contrast, the nanoparticles were not observed in native HeLa cells (without unnatural carbohydrates). These results indicate that the hydrazide groups of the nanoparticles selectively reacted to the ketone groups of the carbohydrates on the cell surface. The PMBH nanoparticles immobilized with anticancer drugs such as doxorubicin or paclitaxel were in contact with either ManLev-treated or untreated HeLa cells. The viability of the ManLev-treated HeLa cells was effectively reduced, but that of the untreated cells was preserved. This indicated that the anticancer drugs were selectively delivered to the ManLev-treated cells. Nonspecific cellular uptake of the nanoparticles was effectively reduced by MPC polymer coating. Furthermore, the immobilization processes of the drugs differed because of the solubility of the drugs. In conclusion, cellular-specific drug delivery by means of the novel nanoparticles was demonstrated with the selective reaction between unnatural carbohydrates on the cell surface and the hydrazide groups bearing the phosphorylcholine polymer nanoparticles.
Authors:
Yasuhiko Iwasaki; Haruki Maie; Kazunari Akiyoshi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-21
Journal Detail:
Title:  Biomacromolecules     Volume:  8     ISSN:  1525-7797     ISO Abbreviation:  Biomacromolecules     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-08     Completed Date:  2007-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3162-8     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita-Shi, Osaka, Japan. yasu.bmt@ipcku.kansai-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / administration & dosage
Carbohydrates / chemistry*
Cell Membrane / metabolism*
Chemistry, Pharmaceutical / methods*
Drug Carriers*
Drug Delivery Systems
Hela Cells
Humans
Methacrylates / chemistry
Microscopy, Fluorescence
Microscopy, Phase-Contrast
Nanoparticles / chemistry*
Phosphorylcholine / analogs & derivatives,  chemistry
Polymers / chemistry
Spectrometry, X-Ray Emission
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Carbohydrates; 0/Drug Carriers; 0/Methacrylates; 0/Polymers; 107-73-3/Phosphorylcholine; 67881-98-5/2-methacryloyloxyethyl phosphorylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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