Polymer genomics: Shifting the gene and drug delivery paradigms

Alexander V. Kabanov, Elena V. Batrakova, Srikanth Sriadibhatla, Zhihui Yang, David Lee Kelly, Valery Yu Alakov

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)259-271
Number of pages13
JournalJournal of Controlled Release
Volume101
Issue number1-3 SPEC. ISS.
DOIs
StatePublished - Jan 3 2005

Fingerprint

Genomics
Polymers
Poloxamer
Pharmacogenetics
Pharmaceutical Preparations
Genes
Antineoplastic Combined Chemotherapy Protocols
Up-Regulation
Polyethyleneimine
Ethylene Oxide
Multiple Drug Resistance
Therapeutic Uses
Drug Delivery Systems
Transgenes
Reporter Genes
Antineoplastic Agents
Doxorubicin
Toxicology
Pharmacology
Breast Neoplasms

Keywords

  • Anthracycline antibiotics
  • Block copolymer
  • Cancer
  • Gene delivery
  • Gene expression
  • Multidrug resistance
  • P-glycoprotein
  • Poloxamer

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Kabanov, A. V., Batrakova, E. V., Sriadibhatla, S., Yang, Z., Kelly, D. L., & Alakov, V. Y. (2005). Polymer genomics: Shifting the gene and drug delivery paradigms. Journal of Controlled Release, 101(1-3 SPEC. ISS.), 259-271. https://doi.org/10.1016/j.jconrel.2004.07.009

Polymer genomics : Shifting the gene and drug delivery paradigms. / Kabanov, Alexander V.; Batrakova, Elena V.; Sriadibhatla, Srikanth; Yang, Zhihui; Kelly, David Lee; Alakov, Valery Yu.

In: Journal of Controlled Release, Vol. 101, No. 1-3 SPEC. ISS., 03.01.2005, p. 259-271.

Research output: Contribution to journalArticle

Kabanov, AV, Batrakova, EV, Sriadibhatla, S, Yang, Z, Kelly, DL & Alakov, VY 2005, 'Polymer genomics: Shifting the gene and drug delivery paradigms', Journal of Controlled Release, vol. 101, no. 1-3 SPEC. ISS., pp. 259-271. https://doi.org/10.1016/j.jconrel.2004.07.009
Kabanov AV, Batrakova EV, Sriadibhatla S, Yang Z, Kelly DL, Alakov VY. Polymer genomics: Shifting the gene and drug delivery paradigms. Journal of Controlled Release. 2005 Jan 3;101(1-3 SPEC. ISS.):259-271. https://doi.org/10.1016/j.jconrel.2004.07.009
Kabanov, Alexander V. ; Batrakova, Elena V. ; Sriadibhatla, Srikanth ; Yang, Zhihui ; Kelly, David Lee ; Alakov, Valery Yu. / Polymer genomics : Shifting the gene and drug delivery paradigms. In: Journal of Controlled Release. 2005 ; Vol. 101, No. 1-3 SPEC. ISS. pp. 259-271.
@article{9fc02b7485cf44829772e6a96c06113a,
title = "Polymer genomics: Shifting the gene and drug delivery paradigms",
abstract = "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.",
keywords = "Anthracycline antibiotics, Block copolymer, Cancer, Gene delivery, Gene expression, Multidrug resistance, P-glycoprotein, Poloxamer",
author = "Kabanov, {Alexander V.} and Batrakova, {Elena V.} and Srikanth Sriadibhatla and Zhihui Yang and Kelly, {David Lee} and Alakov, {Valery Yu}",
year = "2005",
month = "1",
day = "3",
doi = "10.1016/j.jconrel.2004.07.009",
language = "English (US)",
volume = "101",
pages = "259--271",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1-3 SPEC. ISS.",

}

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 Lee

AU - Alakov, Valery Yu

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

UR - http://www.scopus.com/inward/record.url?scp=10044286151&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10044286151&partnerID=8YFLogxK

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 -