Targeted hyperthermia using magnetite cationic liposomes and an alternating magnetic field in a mouse osteosarcoma model

Abstract

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45 degrees C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia. The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung.

Liposomal Drug Delivery: A Versatile Platform for Challenging Clinical Applications

“…Magnetic liposomes provide permeability and controllable release (138)(139). Magnetic liposomes are decorated with various surface ligands, such as polyethylene glycol, as targeting ligands (140), and are bi-functional which means they can carry fluorescent probe and MRI contrast agents for imaging as well as functional DNA delivery to the same cell (141). Recent research has reported super magnetic liposomes to treat cancer tissues and their metastasis without involving surgery or chemotherapeutic agents (142).…”

Tissue Morphology and Gene Expression Characterisation of Transplantable Adenocarcinoma Bearing Mice Exposed to Fluorodeoxyglucose-Conjugated Magnetic Nanoparticles

“…[14][15][16][17] In addition, the use of magnetic field stimulation to induce tumour cell hyperthermia following intravenous administration of MNPs has been shown to be beneficial in controlling tumour growth. [18][19][20][21] Recently, we tested the in vitro functionality of fludeoxyglucose-conjugated magnetic nanoparticles (FDG-MNPs) with the aim of targeting MCF-7 cancer cells in vitro by magnetic field stimulation. As cancer cells are characterised by increased glycolysis and elevated lactate production, 22 23 a phenomenon known as the Warburg effect, 24 their higher metabolic status results in preferential uptake of FDG-MNPs over non-cancerous cells.…”

Intravenous magnetic nanoparticle cancer hyperthermia

“…26 Much progress has also been made in developing better quality magnetic nanoparticles that: are constructed using high temperature crystallization; 27 heat better; 28,29 have different coatings, such as dextran, 30,31 polyethylene glycol (PEG), 32 dopamine, 33 silanes, 34 and gold; 35,36 have low Curie temperatures for heat control; 37 and for liposomal encapsulation. 17,[38][39][40] Direct intratumoral injections of MNPs followed by induction heating has shown some benefit in controlling tumor growth. 38,[41][42][43][44][45][46][47][48][49] Direct intratumoral injection was used in the first MNP hyperthermia clinical trial treating a prostate cancer using a 100 kHz machine designed for human patients, 50 and later in human glioma trials 51,52 which demonstrated safety and some benefit.…”

“…17,[38][39][40] Direct intratumoral injections of MNPs followed by induction heating has shown some benefit in controlling tumor growth. 38,[41][42][43][44][45][46][47][48][49] Direct intratumoral injection was used in the first MNP hyperthermia clinical trial treating a prostate cancer using a 100 kHz machine designed for human patients, 50 and later in human glioma trials 51,52 which demonstrated safety and some benefit. Heating was obtained, but due to inhomogeneous MNP distribution, complete tumor eradication was not possible.…”