Comparison of iron oxide nanoparticle and microwave hyperthermia alone or combined with cisplatinum in murine breast tumors

Abstract

Surgery, radiation and chemotherapy are currently the most commonly used cancer therapies. Hyperthermia has been shown to work effectively with radiation and chemotherapy cancer treatments. The major obstacle faced by previous hyperthermia techniques has been the inability to deliver heat to the tumor in a precise manner. The ability to deliver cytotoxic hyperthermia to tumors (from within individual cells) via iron oxide magnetic nanoparticles (mNP) is a promising new technology that has the ability to greatly improve the therapeutic ratio of hyperthermia as an individual modality and as an adjuvant therapy in combination with other modalities. Although the parameters have yet to be conclusively defined, preliminary data suggests mNP hyperthermia can achieve greater cytotoxicity (in vitro) than conventional water bath hyperthermia methods. At this time, our theory is that intracellular nanoparticle heating is more effective in achieving the combined effect than extracellular heating techniques.1 However, understanding the importance of mNP association and uptake is critical in understanding the potential novelty of the heating modality. Our preliminary data suggests that the mNP heating technique, which did not provide time for particle uptake by the cells, resulted in similar efficacy to microwave hyperthermia. mNP hyperthermia/cisplatinum results have shown a tumor growth delay greater than either modality alone at comparable doses Methods One hour before nanoparticle hyperthermia, CDDP chemotherapy (5mg/kg of body mass) was delivered intraperitoneally (IP). Iron oxide nanoparticles, 7.5mg of iron per gram of tumor, were injected into MTGB flank tumors in female C3H mice immediately before activation. A 170 KHz, 400-450 Oe alternating magnetic field (AMF) was used to induce particle heating. A comparison of nanoparticle induced hyperthermia to non-nanoparticle induced hyperthermia was also made using a 915 MHz microwave generator. Treatment duration was determined by the use of the cumulative equivalent minutes (CEM) algorithm. A CEM 60 was selected as the thermal dose for all experimental groups. Results 1) Preliminary mNP hyperthermia/cisplatinum results have shown a tumor growth delay greater than either modality alone at comparable doses. 2) mNP hyperthermia delivered 10 minutes post mNP injection and microwave hyperthermia, with the same thermal dose, demonstrate similar treatment efficacy.

Hyperthermia approaches for enhanced delivery of nanomedicines to solid tumors

“…However, evidence suggests that hyperthermia can be effective in improving flow throughout these tumors that can overcome some of the biological barriers to delivery when significant localized heating is achieved. Increases in blood flow and accumulation have been observed both during and after hyperthermia (Khandhar et al, ; Petryk et al, ).…”

Advances with metal oxide-based nanoparticles as MDR metastatic breast cancer therapeutics and diagnostics

“…121 Sensitivity of the tumor cells to hyperthermia depends on several factors such as pH, oxygen concentration and cell nutrient level. 122 Preclinical trials have demonstrated that combination of hyperthermia with chemotherapy have enhanced cytotoxicity on tumor cells. 123 Iron oxide NPs with ligands can be utilized in case of specic types of breast cancer for targeted hyperthermia therapy or injected into the tumor tissues for nonspecic hyperthermia.…”

“…The investigation demonstrated that magnetic nanoparticle-based hyperthermia therapy has improved signicantly over conventional hyperthermia treatments. 122 The SPION (e.g., MF66) were electrostatically conjugated with either Nucant multivalent pseudopeptide (N6L; MF66-N6L), doxorubicin (DOX; MF66-DOX) or both (MF66-N6L-DOX). Cytotoxicity of these drugs was examined utilizing MDA-MB-231 breast tumor cells, whereas healing efficiency was examined with subcutaneous MDA-MB-231, TNBC tumor in mice.…”

Understanding Nanoparticle Toxicity to Direct a Safe-by-Design Approach in Cancer Nanomedicine

“…Magnetic nanoparticles allow the supply of tumor-specific hyperthermia intracellularly at the nanoscale level [134]. This can greatly improve the therapeutic efficacy of hyperthermia, concentrating the particles in the tumor and achieving better homogeneity [135]. An alternating magnetic field (AMF) is then applied, heating tumor cells to eradicate/damage cancerous cells.…”