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

Uyanga Tsedev, Ching Wei Lin, Gaelen T. Hess, Jann N. Sarkaria, Fred C. Lam, Angela M. Belcher

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)11676-11691
Number of pages16
JournalACS Nano
Volume16
Issue number8
DOIs
StatePublished - Aug 23 2022

Keywords

  • engineered m13 bacteriophage
  • glioblastoma targeting
  • materials and gene delivery
  • nanotheranostic particle
  • short-wavelength infrared imaging

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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