On-Command Drug Release from Nanochains Inhibits Growth of Breast Tumors |
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Authors: | Pubudu M Peiris Morgan Tam Peter Vicente Aaron Abramowski Randall Toy Lisa Bauer Aaron Mayer Jenna Pansky Elizabeth Doolittle Samantha Tucci Erik Schmidt Christopher Shoup Swetha Rao Kaitlyn Murray Ramamurthy Gopalakrishnan Ruth A Keri James P Basilion Mark A Griswold Efstathios Karathanasis |
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Institution: | 1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA 2. Department of Radiology, Case Western Reserve University, Cleveland, Ohio, USA 3. Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio, USA 4. Department of Physics, Case Western Reserve University, Cleveland, Ohio, USA 5. Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA 6. Case Comprehensive Cancer Center, Case Western Reserve University, Wickenden Bldg. MS 7207, 10900 Euclid Ave., Cleveland, Ohio, 44106, USA
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Abstract: | Purpose To evaluate the ability of radiofrequency (RF)-triggered drug release from a multicomponent chain-shaped nanoparticle to inhibit the growth of an aggressive breast tumor. Methods A two-step solid phase chemistry was employed to synthesize doxorubicin-loaded nanochains, which were composed of three iron oxide nanospheres and one doxorubicin-loaded liposome assembled in a 100-nm-long linear nanochain. The nanochains were tested in the 4T1-Luc-GFP orthotopic mouse model, which is a highly aggressive breast cancer model. The 4T1-Luc-GFP cell line stably expresses firefly luciferase, which allowed the non-invasive in vivo imaging of tumor response to the treatment using bioluminescence imaging (BLI). Results Longitudinal BLI imaging showed that a single nanochain treatment followed by application of RF resulted in an at least 100-fold lower BLI signal compared to the groups treated with nanochains (without RF) or free doxorubicin followed by RF. A statistically significant increase in survival time of the nanochain-treated animals followed by RF (64.3 days) was observed when compared to the nanochain-treated group without RF (35.7 days), free doxorubicin-treated group followed by RF (38.5 days), and the untreated group (30.5 days; n?=?5 animals per group). Conclusions These studies showed that the combination of RF and nanochains has the potential to effectively treat highly aggressive cancers and prolong survival. |
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