Novel Cisplatin-Magnetosome Complex Shows Enhanced Antitumor Activity via Hyperthermia

Abstract There are many approaches to enhance the survival rate of cancer patients based on hyperthermia of tumor tissues, increasing their temperature above 41°C. These approaches use different energy sources to deliver the desired heat to the target region, including light, microwaves or radiofrequency electromagnetic fields. We have developed a new, magnetically responsive nanovector, composed by liposomes loaded with magnetic nanoparticles and cis-diamminedichloroplatinum (II) (CDDP), which is commonly known as Cisplatin. The resulting synthetic magnetosome (SM) is rapidly internalized by lung and pancreas tumor cell lines, stored in intracellular vesicles, and capable of inducing hyperthermia under magnetic fields. Additionally, it efficiently releases the cytotoxic drug upon an increase in temperature. The SM has no significant toxicity both in vitro and in vivo and, most importantly, enhances cell death by apoptosis after magnetic hyperthermia. This indicates that the intracellular release of low-dose CDDP increases the antitumor effect over CDDP-encapsulated liposomes and empty SM. Remarkably, mice bearing induced lung tumors, treated with CDDP-loaded nanovectors and subjected to an applied electromagnetic field, showed an improved survival rate over those treated with either soluble CDDP or hyperthermia alone. Therefore, our approach of magnetic hyperthermia plus CDDP- SM significantly enhances in vitro cell death and in vivo survival of treated animals.