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" Biodistribution of Antibody-MS2 Viral Capsid Conjugates in Breast Cancer Models. "
Aanei, Ioana L; ElSohly, Adel M; Farkas, Michelle E; Netirojjanakul, Chawita; Regan, Melanie; Taylor Murphy, Stephanie; O'Neil, James P; Seo, Youngho; Francis, Matthew B
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AL
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| Record Number
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909238
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LA3d9200b7
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| Title & Author
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Biodistribution of Antibody-MS2 Viral Capsid Conjugates in Breast Cancer Models. [Article]\ Aanei, Ioana L; ElSohly, Adel M; Farkas, Michelle E; Netirojjanakul, Chawita; Regan, Melanie; Taylor Murphy, Stephanie; O'Neil, James P; Seo, Youngho; Francis, Matthew B
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2016
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| Title of Periodical
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UC Berkeley
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| Abstract
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A variety of nanoscale scaffolds, including virus-like particles (VLPs), are being developed for biomedical applications; however, little information is available about their in vivo behavior. Targeted nanoparticles are particularly valuable as diagnostic and therapeutic carriers because they can increase the signal-to-background ratio of imaging agents, improve the efficacy of drugs, and reduce adverse effects by concentrating the therapeutic molecule in the region of interest. The genome-free capsid of bacteriophage MS2 has several features that make it well-suited for use in delivery applications, such as facile production and modification, the ability to display multiple copies of targeting ligands, and the capacity to deliver large payloads. Anti-EGFR antibodies were conjugated to MS2 capsids to construct nanoparticles targeted toward receptors overexpressed on breast cancer cells. The MS2 agents showed good stability in physiological conditions up to 2 days and specific binding to the targeted receptors in in vitro experiments. Capsids radiolabeled with 64Cu isotopes were injected into mice possessing tumor xenografts, and both positron emission tomography-computed tomography (PET/CT) and scintillation counting of the organs ex vivo were used to determine the localization of the agents. The capsids exhibit surprisingly long circulation times (10-15% ID/g in blood at 24 h) and moderate tumor uptake (2-5% ID/g). However, the targeting antibodies did not lead to increased uptake in vivo despite in vitro enhancements, suggesting that extravasation is a limiting factor for delivery to tumors by these particles.
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