PhD Scientific Days 2024

Budapest, 9-10 July 2024

Theoretical and Translational Medicine I.

Modulated Electro-hyperthermia Accelerates Tumour Delivery of Doxorubicin from Lyso-thermosensitive Liposome and Improves its Anticancer Activity in 4T1-Bearing Mice

Author(s)

Kenan Aloss1, Syeda Mahak Zahra Bokhari1, Pedro Henrique Leroy Viana1, Nino Giunashvili1, Csaba András Schvarcz1, Gábor Szénási1, Zoltán Benyó1, Péter Hamar1
1: Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary

Text of the abstract

Introduction and Aim:
Modulated electro-hyperthermia (mEHT) is an advanced option in the hyperthermia field, applying 13.56 Radiofrequency electromagnetic current. By the autofocusing of mEHT the selective and significant (+2.5°C) heating of even deeply situated tumors is possible. In this study, we investigated the possibility of using mEHT as a source of heat for thermosensitive liposomes (TSLs) to effectively enhance the delivery and in vivo efficacy of doxorubicin (DOX).
Methods:
a triple-negative breast cancer cell line (4T1), was orthotopically injected into Balb/C mice and treated with a combination of mEHT and lyso- thermosensitive liposomal doxorubicin (LTLD). Tumor growth was followed by ultrasound and caliper. DOX accumulation in the tumor was assessed by in vivo imaging system (IVIS).
Results:
LTLD+ mEHT combination was more effective in tumor growth inhibition compared to free DOX and pegylated liposomal DOX (PLD) as demonstrated by both tumor volume and tumor weight reduction. Furthermore, LTLD combined with mEHT resulted in the highest DOX accumulation in the tumor at 1 h after treatment. Moreover, cancer cell damage was associated with upregulation of cleaved caspase-3 (cC3) in the damaged area, and reduction of Ki67 in the living area of (mEHT+ LTLD)- treated tumors.
Conclusion:
LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.
Funding:
ID: ÚNKP-23-3-II-SE-45, SE250+ EFOP-3.6.3-VEKOP-16-2017-00009, Tempus Stipendium Hungaricum