Document Detail


In vivo antitumor activity of the folate-conjugated pH-sensitive polymeric micelle selectively releasing adriamycin in the intracellular acidic compartments.
MedLine Citation:
PMID:  17488066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer treatment efficacy and safety of the environmentally sensitive polymeric micelle drug carriers were significantly increased by optimizing the number of ligands on their surface. These micelles were designed to target the cancerous tumors through the interaction between folate and its receptors that overexpress on the cancer cell membrane while achieving pH-controlled drug release in the intracellular acidic compartments such as endosomes and lysosomes. In order to elucidate the effects of folate on cytotoxicity, biodistribution, anticancer activity, and pharmacological properties, folate concentration on the surface of the micelles was controlled by precise synthesis of two different amphiphilic block copolymers that self-assemble into spherical micelles, folate-poly(ethylene glycol)-poly(aspartate-hydrazone-adriamycin) with gamma-carboxylic acid activated folate and methoxy-poly(ethylene glycol)-poly(aspartate-hydrazone-adriamycin) without folate. It is of significance that, although folate conjugation induced an extremely small change in tumor accumulation of the micelles, folate-conjugated micelles showed lower in vivo toxicity and higher antitumor activity over a broad range of the dosage from 7.50 to 26.21 mg/kg, which was 5-fold broader than free drugs.
Authors:
Younsoo Bae; Nobuhiro Nishiyama; Kazunori Kataoka
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Publication Detail:
Type:  Journal Article     Date:  2007-05-09
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  18     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:    2007 Jul-Aug
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1131-9     Citation Subset:  IM    
Affiliation:
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / administration & dosage*,  chemistry,  pharmacokinetics
Cell Survival / drug effects
Doxorubicin / administration & dosage*,  chemistry,  pharmacokinetics
Drug Carriers / administration & dosage,  chemistry,  pharmacokinetics
Female
Folic Acid / administration & dosage*,  chemistry,  pharmacokinetics
Humans
Hydrogen-Ion Concentration
KB Cells
Mice
Mice, Nude
Micelles*
Neoplasm Transplantation
Neoplasms / drug therapy,  metabolism
Polymers / administration & dosage*,  chemistry,  pharmacokinetics
Tumor Burden / drug effects
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Drug Carriers; 0/Micelles; 0/Polymers; 23214-92-8/Doxorubicin; 59-30-3/Folic Acid

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


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