Chemo-immunotherapy of colon cancer with focused ultrasound and Salmonella-laden temperature sensitive liposomes (thermobots)

Scientific Reports
Kalyani EktateAshish Ranjan

Abstract

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 °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 (~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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Citations

Jun 6, 2019·Chemical Society Reviews·Wei SangXiaoyuan Chen
Jul 22, 2020·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Chun ChenJianzhong Zou
Apr 24, 2019·Nanomaterials·Beatriz García-PinelJuan M López-Romero
Mar 17, 2020·Drug Delivery and Translational Research·Arpit BhargavaPradyumna Kumar Mishra
Oct 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jordan B JoinerPaul A Dayton
Jan 12, 2021·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Michael-Joseph GorbetAshish Ranjan
Mar 8, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Guanglong MaWafa T Al-Jamal
Apr 1, 2021·International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group·Ashish RanjanSunil More
May 1, 2021·Pharmaceutics·Tianqi WangJie Shen
Jun 14, 2021·Seminars in Cancer Biology·Muhammad Jameel Mughal, Hang Fai Kwok
Aug 16, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Eskandar MoghimipourSomayeh Handali

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Methods Mentioned

BETA
flow
fluorescence spectroscopy
flow cytometry
ELISA
dynamic light scattering
FACS
enzyme linked immunosorbent assay
PCR

Software Mentioned

Metamorph
FlowJo
GraphPad Prism
2000
VIFU
BD FACS Diva
GraphPad

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