Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy

Sang Min Lee; Richard W. Ahn; Feng Chen; Angela J. Fought; Thomas V. Ohalloran; Vincent L. Cryns; Sonbinh T. Nguyen

doi:10.1021/nn100560p

Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy

Sang Min Lee, Richard W. Ahn, Feng Chen, Angela J. Fought, Thomas V. Ohalloran, Vincent L. Cryns, Sonbinh T. Nguyen

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

70 Scopus citations

Abstract

A series of doxorubicin-loaded polymer-caged nanobins (PCN_DXR) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCN_DXR offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCN_DXR, and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCN_DXR can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCN_DXR was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy.

Original language	English (US)
Pages (from-to)	4971-4978
Number of pages	8
Journal	ACS Nano
Volume	4
Issue number	9
DOIs	https://doi.org/10.1021/nn100560p
State	Published - Sep 28 2010
Externally published	Yes

Keywords

breast cancer
in vivo drug delivery
liposome
pH-responsive release
polymers

ASJC Scopus subject areas

General Materials Science
General Engineering
General Physics and Astronomy

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10.1021/nn100560p

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title = "Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy",

abstract = "A series of doxorubicin-loaded polymer-caged nanobins (PCNDXR) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCNDXR offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCNDXR, and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCNDXR can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCNDXR was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy.",

keywords = "breast cancer, in vivo drug delivery, liposome, pH-responsive release, polymers",

author = "Lee, {Sang Min} and Ahn, {Richard W.} and Feng Chen and Fought, {Angela J.} and Ohalloran, {Thomas V.} and Cryns, {Vincent L.} and Nguyen, {Sonbinh T.}",

year = "2010",

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doi = "10.1021/nn100560p",

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AU - Lee, Sang Min

AU - Ahn, Richard W.

AU - Chen, Feng

AU - Fought, Angela J.

AU - Ohalloran, Thomas V.

AU - Cryns, Vincent L.

AU - Nguyen, Sonbinh T.

PY - 2010/9/28

Y1 - 2010/9/28

N2 - A series of doxorubicin-loaded polymer-caged nanobins (PCNDXR) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCNDXR offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCNDXR, and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCNDXR can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCNDXR was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy.

AB - A series of doxorubicin-loaded polymer-caged nanobins (PCNDXR) were evaluated in vivo in a murine MDA-MB-231 xenograft model of triple-negative breast cancer. The cross-linked polymer cage in PCNDXR offers protection for the drug payload while serving as a pH-responsive trigger that enhances drug release in the acidic environments commonly seen in solid tumors and endosomes. Varying the degree of cross-linking in the polymer cage allows the surface potential of PCNDXR, and thus the in vivo circulation lifetime of the nanocarriers, to be tuned in a facile fashion. Given these design advantages, the present study provides the first in vivo evidence that PCNDXR can effectively inhibit tumor growth in a murine model of breast cancer. Importantly, PCNDXR was well-tolerated by mice, and drug encapsulation attenuated the toxicity of free doxorubicin. Taken together, this study demonstrates the potential utility of the PCN platform in cancer therapy.

KW - breast cancer

KW - in vivo drug delivery

KW - liposome

KW - pH-responsive release

KW - polymers

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Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy

Abstract

Keywords

ASJC Scopus subject areas

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