4.8 Article

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

Journal

ACS NANO
Volume 4, Issue 9, Pages 4971-4978

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/nn100560p

Keywords

liposomes; polymers; breast cancer; pH-responsive release; in vivo drug delivery

Funding

  1. NIH (NCI Center of Cancer Nanotechnology Excellence [U54CA119341, P30CA060553]
  2. Rosenberg Family Cancer Research Fund
  3. CD-MRP Breast Cancer Research [BC073413]

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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.

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