Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor

Jing Li; David Oupický

doi:10.1016/j.biomaterials.2014.03.047

Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor

Jing Li, David Oupický

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Chemokine receptor CXCR4 and its sole ligand SDF-1 are key players in regulating cancer cell invasion and metastasis. Plerixafor (AMD3100) is a small-molecule CXCR4 antagonist that prevents binding of SDF-1 to CXCR4 and has potential in prevention of cancer metastasis. This study investigates the influence of biodegradability of a recently reported polymeric Plerixafor (PAMD) on CXCR4 antagonism, antimetastatic activity, and transfection efficacy of PAMD polyplexes with plasmid DNA. We show that PAMD exhibits CXCR4 antagonism and inhibition of cancer cell invasion invitro regardless of its biodegradability. Biodegradable PAMD showed considerably enhanced transfection efficiency and decreased cytotoxicity when compared with the non-degradable PAMD. Despite similar CXCR4 antagonism invitro, only biodegradable PAMD displayed antimetastatic activity in experimental lung metastasis model invivo.

Original language	English (US)
Pages (from-to)	5572-5579
Number of pages	8
Journal	Biomaterials
Volume	35
Issue number	21
DOIs	https://doi.org/10.1016/j.biomaterials.2014.03.047
State	Published - Jul 2014

Keywords

Bioreducible polycation
CXCR4
Gene delivery
Metastasis
Polyplexes

ASJC Scopus subject areas

Bioengineering
Ceramics and Composites
Biophysics
Biomaterials
Mechanics of Materials

Access to Document

10.1016/j.biomaterials.2014.03.047

Fingerprint Dive into the research topics of 'Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor'. Together they form a unique fingerprint.

Cite this

@article{45f38619f58d48e69f3a8fbd1785b73b,

title = "Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor",

abstract = "Chemokine receptor CXCR4 and its sole ligand SDF-1 are key players in regulating cancer cell invasion and metastasis. Plerixafor (AMD3100) is a small-molecule CXCR4 antagonist that prevents binding of SDF-1 to CXCR4 and has potential in prevention of cancer metastasis. This study investigates the influence of biodegradability of a recently reported polymeric Plerixafor (PAMD) on CXCR4 antagonism, antimetastatic activity, and transfection efficacy of PAMD polyplexes with plasmid DNA. We show that PAMD exhibits CXCR4 antagonism and inhibition of cancer cell invasion invitro regardless of its biodegradability. Biodegradable PAMD showed considerably enhanced transfection efficiency and decreased cytotoxicity when compared with the non-degradable PAMD. Despite similar CXCR4 antagonism invitro, only biodegradable PAMD displayed antimetastatic activity in experimental lung metastasis model invivo.",

keywords = "Bioreducible polycation, CXCR4, Gene delivery, Metastasis, Polyplexes",

author = "Jing Li and David Oupick{\'y}",

year = "2014",

month = jul,

doi = "10.1016/j.biomaterials.2014.03.047",

language = "English (US)",

volume = "35",

pages = "5572--5579",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "21",

}

TY - JOUR

T1 - Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor

AU - Li, Jing

AU - Oupický, David

PY - 2014/7

Y1 - 2014/7

N2 - Chemokine receptor CXCR4 and its sole ligand SDF-1 are key players in regulating cancer cell invasion and metastasis. Plerixafor (AMD3100) is a small-molecule CXCR4 antagonist that prevents binding of SDF-1 to CXCR4 and has potential in prevention of cancer metastasis. This study investigates the influence of biodegradability of a recently reported polymeric Plerixafor (PAMD) on CXCR4 antagonism, antimetastatic activity, and transfection efficacy of PAMD polyplexes with plasmid DNA. We show that PAMD exhibits CXCR4 antagonism and inhibition of cancer cell invasion invitro regardless of its biodegradability. Biodegradable PAMD showed considerably enhanced transfection efficiency and decreased cytotoxicity when compared with the non-degradable PAMD. Despite similar CXCR4 antagonism invitro, only biodegradable PAMD displayed antimetastatic activity in experimental lung metastasis model invivo.

AB - Chemokine receptor CXCR4 and its sole ligand SDF-1 are key players in regulating cancer cell invasion and metastasis. Plerixafor (AMD3100) is a small-molecule CXCR4 antagonist that prevents binding of SDF-1 to CXCR4 and has potential in prevention of cancer metastasis. This study investigates the influence of biodegradability of a recently reported polymeric Plerixafor (PAMD) on CXCR4 antagonism, antimetastatic activity, and transfection efficacy of PAMD polyplexes with plasmid DNA. We show that PAMD exhibits CXCR4 antagonism and inhibition of cancer cell invasion invitro regardless of its biodegradability. Biodegradable PAMD showed considerably enhanced transfection efficiency and decreased cytotoxicity when compared with the non-degradable PAMD. Despite similar CXCR4 antagonism invitro, only biodegradable PAMD displayed antimetastatic activity in experimental lung metastasis model invivo.

KW - Bioreducible polycation

KW - CXCR4

KW - Gene delivery

KW - Metastasis

KW - Polyplexes

UR - http://www.scopus.com/inward/record.url?scp=84899483825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899483825&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2014.03.047

DO - 10.1016/j.biomaterials.2014.03.047

M3 - Article

C2 - 24726746

AN - SCOPUS:84899483825

VL - 35

SP - 5572

EP - 5579

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 21

ER -