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 <i>in vivo</i> 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 <i>in vitro</i> 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 <i>ex vivo</i> 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 <i>in vivo</i> despite <i>in vitro</i> enhancements, suggesting that extravasation is a limiting factor for delivery to tumors by these particles