Document Detail


Intracellular delivery of the reactive oxygen species generating agent D-penicillamine upon conjugation to poly-L-glutamic acid.
MedLine Citation:
PMID:  20349949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
D-penicillamine is an aminothiol that is cytotoxic to cancer cells and generates dose dependent reactive oxygen species (ROS) via copper catalyzed oxidation. However, the delivery of D-pen to cancer cells remains a challenge due to its high hydrophilicity, highly reactive thiol group and impermeability to the cell membrane. To overcome this challenge, we investigated a novel poly-L-glutamic acid (PGA) conjugate of D-pen (PGA-D-pen) where D-pen was conjugated to PGA modified with 2-(2-pyridyldithio)-ethylamine (PDE) via disulfide bonds. Confocal microscopy and cell uptake studies showed that the fluorescently labeled PGA-D-pen was taken up by human leukemia cells (HL-60) in a time dependent manner. Treatment of HL-60, murine leukemia cells (P388) and human breast cancer cells (MDA-MB-468) with PGA-D-pen resulted in dose dependent cytotoxicity and elevation of intracellular ROS levels. PGA-D-pen induced apoptosis in HL-60 cells which was verified by Annexin V binding. The in vivo evaluation of the conjugate in the P388 murine leukemia model (intraperitoneal) resulted in significant enhancement in the survival of CD2F1 mice over vehicle control.
Authors:
Saurabh Wadhwa; Russell J Mumper
Related Documents :
17561369 - Comparison of sensitizers by detecting reactive oxygen species after photodynamic react...
20072909 - Identification of ros using oxidized dcfda and flow-cytometry.
1257749 - Marine oscillatoria (trichodesmium): explanation for aerobic nitrogen fixation without ...
19285719 - Fluorescent microparticles for sensing cell microenvironment oxygen levels within 3d sc...
15299119 - Traffic lights in trichodesmium. regulation of photosynthesis for nitrogen fixation stu...
10650219 - Respiratory pathways and oxygen toxicity in phanerochaete chrysosporium.
23578979 - Isolation and analysis of single cells from the mouse heart.
19544429 - Epidermal growth factor induces the progeny of subventricular zone type b cells to migr...
12819379 - Histochemistry of six lectins in the tissues of the flat fish paralichthys olivaceus.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  7     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-09-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  854-62     Citation Subset:  IM    
Affiliation:
Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina 27599-7362, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Cell Line, Tumor
Chelating Agents / administration & dosage,  chemistry,  pharmacology
Chromatography, High Pressure Liquid
HL-60 Cells
Humans
Mice
Microscopy, Confocal
Molecular Structure
Neoplasms / drug therapy
Penicillamine / administration & dosage*,  chemistry*,  pharmacology
Polyglutamic Acid / chemistry*
Reactive Oxygen Species / metabolism*
Chemical
Reg. No./Substance:
0/Chelating Agents; 0/Reactive Oxygen Species; 25513-46-6/Polyglutamic Acid; 52-67-5/Penicillamine

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


Previous Document:  Development of a novel self-microemulsifying drug delivery system for reducing HIV protease inhibito...
Next Document:  Anticoagulant Efficacy of Solid Oral Formulations Containing a New Heparin Derivative.