Journal
THERANOSTICS
Volume 2, Issue 8, Pages 757-768Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.4756
Keywords
Gold nanorod (GNR); drug delivery; nanoparticles; cancer; positron emission tomography (PET); cRGD peptide; tumor targeting
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Funding
- National Science Foundation [CMMI 1032186]
- University of Wisconsin Carbone Cancer Center
- University of Wisconsin-Madison
- University of Wisconsin-Milwaukee Intercampus grant
- Department of Defense [W81XWH-11-1-0644, W81XWH-11-1-0648]
- NIH [5 T32 CA009206-32]
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A multifunctional gold nanorod (GNR)-based nanoplatform for targeted anticancer drug delivery and positron emission tomography (PET) imaging of tumors was developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX)) was covalently conjugated onto PEGylated (PEG: polyethylene glycol) GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo( Arg-Gly-Asp-D-Phe-Cys) peptides, cRGD) and Cu-64-chelators (i.e., 1,4,7-triazacyclononane-N, N', N ''-triacetic acid (NOTA)) were conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Based on flow cytometry analysis, cRGD-conjugated nanocarriers (i.e., GNR-DOX-cRGD) exhibited a higher cellular uptake and cytotoxicity than non-targeted ones (i.e., GNR-DOX) in vitro. However, GNR-DOX-cRGD and GNR-DOX nanocarriers had similar in vivo biodistribution according to in vivo PET imaging and biodistribution studies. Due to the unique optical properties of GNRs, this multifunctional GNR-based nanoplatform can potentially be optimized for combined cancer therapies (chemotherapy and photothermal therapy) and multimodality imaging (PET, optical, X-ray computed tomography (CT), etc.).
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