Biodistribution of Antibody-MS2 Viral Capsid Conjugates in Breast Cancer Models.
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 with64Cu 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.
Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.|Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratories , Berkeley, California 94720, United States.
Ioana L
IL
Aanei
Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.
Adel M
AM
ElSohly
Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.
Michelle E
ME
Farkas
Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.
Chawita
C
Netirojjanakul
Department of Radiology and Biomedical Imaging, University of California, San Francisco , San Francisco, California 94143, United States.
Melanie
M
Regan
Department of Radiology and Biomedical Imaging, University of California, San Francisco , San Francisco, California 94143, United States.
Stephanie
S
Taylor Murphy
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratories , Berkeley, California 94720, United States.
James P
JP
O'Neil
Department of Radiology and Biomedical Imaging, University of California, San Francisco , San Francisco, California 94143, United States.
Youngho
Y
Seo
Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.|Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratories , Berkeley, California 94720, United States.
Matthew B
MB
Francis
D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D001943:Breast Neoplasms / Q000378:metabolism*; D002213:Capsid / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017909:Levivirus / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D000072078:Positron Emission Tomography Computed Tomography
D000906:Antibodies; D036022:Capsid Proteins
PET imaging; antibody targeting; bacteriophage MS2; bioconjugation; tumor targeting