title: Biological evaluation of pH-responsive polymer-caged nanobins for breast cancer therapy.
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.
authors.affiliation: Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Richard W
authors.initials: RW
authors.lastname: Ahn
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Fought
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Cryns
authors.forename: Sonbinh T
authors.initials: ST
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D050997:Nanomedicine; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
chemical_list: D053769:Nanocapsules; D011108:Polymers; D004317:Doxorubicin