Magnetic hyperthermia induced drug release
from thermosensitive magneto-liposomes
for cancer cells apoptosis

HYPERAEMIA

Project PN-III-P1-1.1-TE-2019-1392

Contract no TE 193 ⁄ 2021

Cancer still remains one of the leading causes of death worldwide and arises when a normal cell undergoes a series of genetic mutations resulting in its uncontrolled cell growth and proliferation, causing malignancy. The mortality rates of a variety of cancer types have only decreased by less than 2%, even though the fight against cancer has been long-standing. The current standard of cancer care comprises the elimination of solid tumors by surgery followed by the treatment with chemotherapeutic drugs. However, it has been shown that the anticancer drugs used in chemotherapy also target other healthy tissues in the body resulting in toxicity to vital organs such as heart in the case of doxorubicin.

On the other hand it was discovered that cancer cells have a greater sensitivity to heat as compared to normal cells. Indeed, healthy tissues are able to withstand temperatures of 42 – 45 °C, in contrast to cancer cells which undergo apoptosis at those temperatures. As a result, the magnetic hyperthermia (MH) based on the MNPs acting as heating sources to raise the temperature of the cancer cells up to a level at which apoptosis can be initiated, has become one of the most promising adjuvant treatment therapy, capable to cure cancer and thus to save millions of lives. However, the complete eradication of cancer tumors cannot be achieved by the application of MH standalone respecting the safety limit. In the best case, the mild heating generated by the internalized MNPs in the safety interval can trigger the differentiation of cancer cells and sensitize fast-dividing cancer cells to other treatments, such as chemotherapy and radiation.

The combination of two independent therapies through one single versatile nano-platform has become a really promising technology in the treatment of cancer. In this regard, combined drug delivery and hyperthermia treatment at a specific target site hold great expectations.  
 
In this project we would like to further extend the very recent advancements in both preparation and application of thermosensitive magneto-liposomes (ThMLs) to cancer treatment with the precise goal of elaborating a new class of biofunctionalized hybrid ThMLs capable to efficiently induce in vitro apoptosis of cancer cells. The precise choice of lipids and the careful adjustment of their amounts in the mixture will give us the opportunity to prepare robust and stealth ThMLs having the transition temperature between 42-43°C, easy attainable by any heating procedure. Cubic superparamagnetic nanoparticles (SPIONs) with high heating power will be synthesized and further introduced in the inner hydrophilic cavity of the liposomes together with anticancer therapeutic drugs to complete the preparation of drug-loaded ThMLs. The high thermal energy delivered by encapsulated cubic SPIONs upon exposure to external AC magnetic field within the safety limit, besides altering the liposomal membrane and render it permeable to encapsulated anticancer drug, will also sensitize the cancer cells to chemotherapy. In other words, the proposed drug-loaded ThMLs, acting as drug carriers, will provide a synergistic therapeutic effect in the treatment of cancer cells via hyperthermia and chemotherapy with triggered drug release.