Phage Particles of Controlled Length and Genome for In Vivo Targeted Glioblastoma Imaging and Therapeutic Delivery

ACS Nano. 2022 Aug 23;16(8):11676-11691. doi: 10.1021/acsnano.1c08720. Epub 2022 Jul 13.

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 "inho" circular single-stranded DNA (cssDNA) gene packaging system, we produced miniature chlorotoxin inho (CTX-inho) 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-inho phage accumulated in brain tumors, facilitating shortwave infrared detection. Furthermore, we show that our inho phage can carry cssDNA that are transcriptionally active when delivered to GBM22 glioma cells in vitro. 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.

Keywords: engineered m13 bacteriophage; glioblastoma targeting; materials and gene delivery; nanotheranostic particle; short-wavelength infrared imaging.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteriophage M13
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / therapy
  • Capsid
  • Capsid Proteins
  • Glioblastoma* / diagnostic imaging
  • Glioblastoma* / genetics
  • Glioblastoma* / therapy
  • Mice

Substances

  • Capsid Proteins