Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice

Kenan Aloss, Syeda Mahak Zahra Bokhari, Pedro Henrique Leroy Viana, Nino Giunashvili, Csaba András Schvarcz, Gábor Szénási, Dániel Bócsi, Zoltán Koós, Gert Storm, Zsuzsanna Miklós, Zoltán Benyó, Péter Hamar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). The 4T1 cells were orthotopically injected into Balb/C mice, and mEHT was performed on days 9, 12, and 15 after the implantation. DOX, LTLD, or PEGylated liposomal DOX (PLD) were administered for comparison. The tumor size and DOX accumulation in the tumor were measured. The cleaved caspase-3 (cC3) and cell proliferation were evaluated by cC3 or Ki67 immunohistochemistry and Western blot. The LTLD+mEHT combination was more effective at inhibiting tumor growth than the free DOX and PLD, demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the tumor one hour after treatment. Tumor cell damage was associated with cC3 in the damaged area, and with a reduction in Ki67 in the living area. These changes were significantly the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.

Original languageEnglish
Article number3101
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume25
Issue number6
DOIs
Publication statusPublished - Mar 2024

Keywords

  • doxorubicin
  • lyso-thermosensitive liposome
  • modulated electro-hyperthermia
  • PEGylated liposome

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