Journal
ACS NANO
Volume 16, Issue 8, Pages 11676-11691Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c08720
Keywords
glioblastoma targeting; short-wavelength infrared imaging; engineered m13 bacteriophage; nanotheranostic particle; materials and gene delivery
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Funding
- DARPA Living Foundries:1,000 Molecules Program [HR0011-15-C-0084]
- Marble Center for Cancer Nanomedicine
- Cancer Center [P30-CA14051]
- Koch Institute student research funds
- Hope Babette Tang (1983) Student Research Fund
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M13 phage can be used as a diagnostic and therapeutic platform, targeting GBM22 glioblastoma tumors and enabling tumor detection through shortwave infrared imaging. They can also deliver transcriptionally active genes to glioma cells in vitro.
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.
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