Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-30106-4
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Funding
- Center for Veterinary Health Sciences
- Kerr
- McCasland Foundation Endowed Chair at Oklahoma State University
- NSF MRI program
- NIH COBRE [P20GM103648]
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Using attenuated Salmonella that efficiently homes in solid tumors, here we developed thermobots that actively transported membrane attached low-temperature sensitive liposome (LTSL) inside colon cancer cells for triggered doxorubicin release and simultaneous polarized macrophages to M1 phenotype with high intensity focused ultrasound (HIFU) heating (40-42 degrees C). Biocompatibility studies showed that the synthesized thermobots were highly efficient in LTSL loading without impacting its viability. Thermobots demonstrated efficient intracellular trafficking, high nuclear localization of doxorubicin, and induced pro-inflammatory cytokine expression in colon cancer cells in vitro. Combination of thermobots and HIFU heating (similar to 30 min) in murine colon tumors significantly enhanced polarization of macrophages to M1 phenotype and therapeutic efficacy in vivo compared to control. Our data suggest that the thermobots and focused ultrasound treatments have the potential to improve colon cancer therapy.
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