PMID- 11710102
OWN - NLM
STAT- MEDLINE
DCOM- 20020117
LR  - 20191105
IS  - 1525-7797 (Print)
IS  - 1525-7797 (Linking)
VI  - 1
IP  - 2
DP  - 2000 Summer
TI  - A hyaluronic acid-taxol antitumor bioconjugate targeted to cancer cells.
PG  - 208-18
AB  - A cell-targeted polymeric prodrug prepared from Taxol and chemically modified 
      hyaluronic acid (HA) was evaluated in vitro. Herein we report four results in 
      support of the selective uptake and targeted toxicity of the HA-Taxol prodrug. 
      First, a fluorescently labeled HA-Taxol (FITC-HA-Taxol) was synthesized and used 
      to demonstrate cell-specific binding and uptake using flow cytometry and confocal 
      microscopy. Second, the selective cytotoxicity of FITC-HA-Taxol allowed direct 
      correlation of uptake with selective cytotoxicity. Third, the rapid uptake and 
      selective cytotoxicity of HA-Taxol bioconjugates could be blocked by either 
      excess HA or by an anti-CD44 antibody, but not by chondroitin sulfate (CS). 
      Finally, the release of free Taxol from HA-Taxol in human plasma or in cell 
      culture media revealed that the free drug was hydrolytically released from the 
      bioconjugate by cleavage of the labile 2' ester linkage. Taken together, these 
      data support the notion that the targeted cytotoxicity of HA-Taxol bioconjugates 
      requires receptor-mediated cellular uptake of the bioconjugate followed by 
      hydrolytic release of free Taxol.
FAU - Luo, Y
AU  - Luo Y
AD  - Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 
      84112-5820, USA.
FAU - Ziebell, M R
AU  - Ziebell MR
FAU - Prestwich, G D
AU  - Prestwich GD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Prodrugs)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - 9007-27-6 (Chondroitin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antibodies, Blocking/pharmacology
MH  - Antineoplastic Agents, Phytogenic/*administration & dosage/antagonists & 
      inhibitors/*pharmacology
MH  - Cell Survival/drug effects
MH  - Chondroitin/pharmacology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Hyaluronan Receptors/immunology
MH  - Hyaluronic Acid/*chemistry
MH  - Indicators and Reagents
MH  - Magnetic Resonance Spectroscopy
MH  - Mice
MH  - Microscopy, Confocal
MH  - Molecular Weight
MH  - Paclitaxel/*administration & dosage/antagonists & inhibitors/*pharmacology
MH  - Prodrugs/*administration & dosage/pharmacology
MH  - Spectrophotometry, Ultraviolet
MH  - Tumor Cells, Cultured
EDAT- 2001/11/17 10:00
MHDA- 2002/01/18 10:01
CRDT- 2001/11/17 10:00
PHST- 2001/11/17 10:00 [pubmed]
PHST- 2002/01/18 10:01 [medline]
PHST- 2001/11/17 10:00 [entrez]
AID - 10.1021/bm000283n [doi]
PST - ppublish
SO  - Biomacromolecules. 2000 Summer;1(2):208-18. doi: 10.1021/bm000283n.