PhD Scientific Days 2023

Budapest, 22-23 June 2023

Translational Medicine II.

Modulated Electro Hyperthermia Enhances the Delivery and Antitumor Effects of Doxorubicin Encapsulated in Lyso-thermosensitive Liposome in 4T1 Mouse Model

Kenan Aloss1, Csaba Schvarcz1, Pedro Leroy1, Nino Guinasvilli1, Mahak Bokhari Zahra1, Daniel Bocsi1, Zoltán Koós1, Peter Hamar1
1 Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary

Text of the abstract

Introduction: Modulated electro hyperthermia (mEHT) is an adjuvant cancer therapy which selectively targets the tumor. 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 inhibition was followed and DOX accumulation in the tumor was monitored by in vivo optical imaging. Results: LTLD+ mEHT combination was more effective in tumor growth inhibition compared to free DOX and pegylated liposomal DOX (PLD- Caelyx) as demonstrated by both tumor volume and tumor weight reduction. Moreover, the highest tumor destruction ratio (TDR) was observed in (LTLD+mEHT) group on HE stained samples. Furthermore, LTLD combined with mEHT resulted in the highest DOX accumulation in the tumor at 1 h and 24 h after treatment. On the other hand, LTLD exhibited similar toxicity to free DOX as demonstrated by body weight loss. In conclusion, mEHT can be an effective tool to improve tumor delivery and anti-tumor activity of DOX-encapsulated in TSL. Funding: SE250 ID: EFOP-3.6.3-VEKOP-16-2017-00009, ÚNKP-22-4-I-SE-15, 2021-1.2.4-TÉT-2021-00060, STIA-OTKA to PH