Phage Particles of Controlled Length and Genome for <i>In Vivo</i> Targeted Glioblastoma Imaging and Therapeutic Delivery

Abstract

M13 bacteriophage (phage) are versatile, genetically tunable nanocarriers that have been recently adapted for use as diagnostic and therapeutic platforms. Applying p3 capsid chlorotoxin fusion with the "<i>inho</i>" circular single-stranded DNA (cssDNA) gene packaging system, we produced miniature chlorotoxin <i>inho</i> (CTX-<i>inho</i>) phage particles with a minimum length of 50 nm that can target intracranial orthotopic patient-derived GBM22 glioblastoma tumors in the brains of mice. Systemically administered indocyanine green conjugated CTX-<i>inho</i> phage accumulated in brain tumors, facilitating shortwave infrared detection. Furthermore, we show that our <i>inho</i> phage can carry cssDNA that are transcriptionally active when delivered to GBM22 glioma cells <i>in vitro</i>. The ability to modulate the capsid display, surface loading, phage length, and cssDNA gene content makes the recombinant M13 phage particle an ideal delivery platform.