Modulated electro-hyperthermia-enhanced liposomal drug uptake by cancer cells

Abstract

Purpose

Modulated electro-hyperthermia (mEHT) stands to be a significant technological advancement in the hyperthermia field, utilizing autofocusing electromagnetic power on the cell membrane to create massive apoptosis. Since mEHT possesses the unique ability to excite cell membranes, we hypothesized that mEHT could enhance the uptake of liposomal drugs by enhancing phagocytic activity.

Materials and methods

Water bath control and mEHT were used to compare the enhancement of liposome-encapsulated doxorubicin (Lipodox^®) uptake by cancer cells. Cancer cells were made visible by doxorubicin fluorescence to investigate drug uptake. Viable cell yield was determined via the Trypan Blue exclusion method. Various substrates were used to investigate the mechanism of drug-uptake enhancement. The murine colon carcinoma model, CT26, was used to confirm the tissue infiltration of Lipodox^® and its therapeutic effect.

Results

mEHT treatment showed a significant enhancement of Lipodox^® uptake of doxorubicin fluorescence compared with 37°C or 42°C water bath treatment. Tumor tissue sections also confirmed that mEHT treatment achieved the highest doxorubicin concentration in vivo (1.44±0.32 µg/g in mEHT group and 0.79±0.32 µg/g in 42°C water bath). Wortmannin was used to inhibit the macropinocytosis effect and 70 kDa dextran-FITC served as uptake substance. The uptake of dextran-FITC by cancer cells significantly increased after mEHT treatment whereas such enhancement was significantly inhibited by wortmannin.

Conclusion

The result showed mEHT-induced particle-uptake through macropinocytosis. mEHT-enhanced uptake of Lipodox^® may amplify the therapeutic effect of liposomal drugs. This novel finding warrants further clinical investigation.

Keywords:

• hyperthermia
• cancer treatment
• liposome
• doxorubicin
• micropinocytosis

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Modulated electro-hyperthermia-enhanced liposomal drug uptake by cancer cells [Corrigendum]

Acknowledgments

The authors would like to thank Mr Winston Han and Dr Tony Tsoi for their editing and proofing of the manuscript. This study was supported by the research fund from the Department of Radiation Oncology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.

Author contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.