期刊
BIOMATERIALS
卷 34, 期 33, 页码 8323-8332出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.07.085
关键词
Unimolecular micelles; Dendritic amphiphilic block copolymer; Nanocarriers; CD105 (endoglin); Molecular imaging; Positron emission tomography (PET)
资金
- National Science Foundation [DMR 1032187]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, R R. China
- National Institutes of Health [NIBIB/NCI 1R01CA169365-01A1]
- Department of Defense [W81XWH-11-1-0644]
- American Cancer Society [125246-RSG-13-099-01-CCE]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1032187] Funding Source: National Science Foundation
Unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine) poly(L-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N, N', N-triacetic acid (NOTA, a macrocyclic chelator for Cu-64) (abbreviated as PAMAM PLA-b-PEG TRC105) were synthesized and characterized. Doxorubicin (DOX), a model anticancer drug, was loaded into the hydrophobic core of the unimolecular micelles formed by PAMAM and PLA via physical encapsulation. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. TRC105-conjugated unimolecular micelles showed a CD105-associated cellular uptake in human umbilical vein endothelial cells (HUVEC) compared with non-targeted unimolecular micelles, which was further validated by cellular uptake in CD105-negative MCF-7 cells. In 4T1 murine breast tumor-bearing mice, Cu-64-labeled targeted micelles exhibited a much higher level of tumor accumulation than Cu-64-labeled non-targeted micelles, measured by serial non-invasive positron emission tomography (PET) imaging and confirmed by biodistribution studies. These unimolecular micelles formed by dendritic amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics. (C) 2013 Elsevier Ltd. All rights reserved.
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