TY - JOUR
T1 - Polymer genomics
T2 - Shifting the gene and drug delivery paradigms
AU - Kabanov, Alexander V.
AU - Batrakova, Elena V.
AU - Sriadibhatla, Srikanth
AU - Yang, Zhihui
AU - Kelly, David L.
AU - Alakov, Valery Yu
N1 - Funding Information:
This work was supported by the US National Institutes of Health grant CA89225, US National Research Foundation grant BES-9907281, and the Nebraska Research Initiative Gene Therapy Program. The assistance of the University of Nebraska Bioinformatics Shared Resource (Dr. S. Sherman) in the analysis of gene expression profiles is acknowledged.
PY - 2005/1/3
Y1 - 2005/1/3
N2 - Pluronic, the A-B-A amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide), can up-regulate the expression of selected genes in cells and alter genetic responses to antineoplastic agents in cancer. Two key new findings are discussed in relation to current drug and gene delivery strategies. First, these block copolymers alone and in combination with a polycation, polyethyleneimine, can up-regulate the expression of reporter genes in stably transfected cells. This underscores the ability of selected synthetic polymers to enhance transgene expression through a mechanism that augments improved DNA delivery into a cell. Second, although, when used alone, Pluronic is "genetically benign," when combined with an antineoplastic agent, doxorubicin, it drastically alters pharmacogenomic responses to this agent and prevents the development of multidrug resistance in breast cancer cells. Collectively, these studies propose the need for a thorough assessment of pharmacogenomic effects of polymer therapeutics to maximize the clinical outcomes and understand the pharmacological and toxicological effects of polymer-based drugs and delivery systems.
AB - Pluronic, the A-B-A amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide), can up-regulate the expression of selected genes in cells and alter genetic responses to antineoplastic agents in cancer. Two key new findings are discussed in relation to current drug and gene delivery strategies. First, these block copolymers alone and in combination with a polycation, polyethyleneimine, can up-regulate the expression of reporter genes in stably transfected cells. This underscores the ability of selected synthetic polymers to enhance transgene expression through a mechanism that augments improved DNA delivery into a cell. Second, although, when used alone, Pluronic is "genetically benign," when combined with an antineoplastic agent, doxorubicin, it drastically alters pharmacogenomic responses to this agent and prevents the development of multidrug resistance in breast cancer cells. Collectively, these studies propose the need for a thorough assessment of pharmacogenomic effects of polymer therapeutics to maximize the clinical outcomes and understand the pharmacological and toxicological effects of polymer-based drugs and delivery systems.
KW - Anthracycline antibiotics
KW - Block copolymer
KW - Cancer
KW - Gene delivery
KW - Gene expression
KW - Multidrug resistance
KW - P-glycoprotein
KW - Poloxamer
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U2 - 10.1016/j.jconrel.2004.07.009
DO - 10.1016/j.jconrel.2004.07.009
M3 - Article
C2 - 15588910
AN - SCOPUS:10044286151
VL - 101
SP - 259
EP - 271
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1-3 SPEC. ISS.
ER -