Nanoparticle-mediated magnetic hyperthermia is an effective method for killing the human-infective protozoan parasite Leishmania mexicana in vitro

Abstract

Cutaneous leishmaniasis is a neglected tropical disease characterized by disfiguring skin lesions. Current chemotherapeutic options depend on toxic, expensive drugs that are both difficult to administer and becoming less effective due to increasing levels of resistance. In comparison, thermotherapy displays greater patient compliance and less adverse systemic effects, but there are still significant issues associated with this. The procedure is painful, requiring local anaesthetic, and is less effective against large lesions. Using nanoparticles to controllably generate heat in a localized manner may provide an alternative solution. Here we evaluate magnetic hyperthermia, using iron oxide magnetic nanoparticles, as a localized, heat-based method to kill the human-infective parasite in vitro. We assessed the effectiveness of this method against the differentiated, amastigote form of the parasite using three distinct viability assays: PrestoBlue, Live/Dead stain and a novel luciferase-based assay. Changes in amastigote morphology and ultrastructure were assessed by immunofluorescence, scanning and transmission electron microscopy. Our findings show that magnetic hyperthermia is an effective method to kill host-infective amastigotes, with morphological changes consistent with heat treatment. This method has the potential to be a step-change for research into new therapeutic options that moves away from the expensive chemotherapeutics currently dominating the research climate.

Establishment, optimisation and quantitation of a bioluminescent murine infection model of visceral leishmaniasis for systematic vaccine screening

“…While several studies have used bioluminescent Leishmania spp. parasites, expressing different types of luciferase for a variety of purposes [31][32][33][34][35] , only a few have fully characterised the VL-infection progression in vivo [36][37][38] . Careful assessment and understanding of how different parameters such as parasite dose, route of administration or how the effects of adjuvant on vaccine formulation may affect experimental infections is important for these models to be useful for both drug and especially vaccine development.…”

Radio frequency plasma assisted surface modification of Fe3O4 nanoparticles using polyaniline/polypyrrole for bioimaging and magnetic hyperthermia applications

“…Superparamagnetic Fe 3 O 4 nanoparticles release thermal energy when subjected to an alternating magnetic field which is due to the Brownian and Neel relaxation [ 5 , 15 ]. This property of superparamagnetic iron oxide nanoparticles (SPIONs) can be used for hyperthermia generation and is effective for the treatment of tumours [ 7 ]. It is reported that cancerous cells are more sensitive to temperature in the range of 42–45 °C than normal tissues [ 6 ].…”

The Intrinsic Biological Identities of Iron Oxide Nanoparticles and Their Coatings: Unexplored Territory for Combinatorial Therapies

“…Indeed, these features make up the physical identity of IONPs, understood as the physical properties intrinsic to the metallic core ( Table 1 and Figure 1 ). Physical identity ultimately determines the biomedical application of metallic nanoparticles in imaging/therapy, and the magnetic properties of IONPs make it possible for them to be used in MRI [ 5 ], magnetic targeting [ 6 , 7 , 8 ] and delivery [ 9 , 10 ], and hyperthermia [ 11 , 12 , 13 ].…”