Biological Evaluation of pH-Responsive Polymer-Caged Nanobins for Breast Cancer Therapy

被引:65
作者
Lee, Sang-Min [1 ,3 ,7 ]
Ahn, Richard W. [1 ,3 ,7 ]
Chen, Feng [3 ,4 ,5 ,7 ]
Fought, Angela J. [6 ,7 ]
O'Halloran, Thomas V. [1 ,2 ,3 ,7 ]
Cryns, Vincent L. [3 ,4 ,5 ,7 ]
Nguyen, SonBinh T. [1 ,3 ,7 ]
机构
[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
[2] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA
[3] Northwestern Univ, Ctr Canc Nanotechnol Excellence, Evanston, IL 60208 USA
[4] Northwestern Univ, Cell Death Regulat Lab, Dept Med, Chicago, IL 60611 USA
[5] Northwestern Univ, Cell Death Regulat Lab, Dept Cell & Mol Biol, Chicago, IL 60611 USA
[6] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA
[7] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA
关键词
liposomes; polymers; breast cancer; pH-responsive release; in vivo drug delivery; FLUORESCENT PROTEINS; SENSITIVE LIPOSOMES; LIGHT-SCATTERING; DELIVERY; TUMOR; THERAPEUTICS; EFFICIENT;
D O I
10.1021/nn100560p
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:4971 / 4978
页数:8
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