Magnetically triggered smart liposomes

Abstract

Event Abstract Back to Event Magnetically triggered smart liposomes Md Shahriar Hossain1*, Boris Martinac2*, Jung Ho Kim1*, M Azam Ali3*, Mislav Mustapic1*, Yoshitaka Nakayama2* and Joseph Horvat1* 1 Institute for Superconducting and Electronic Materials, University of Wollongong, Science and Engineering, Australia 2 Victor Chang Cardiac Research Institute, Mechano Biology Laboratory, Australia 3 University of Otago, Department of Applied Science, New Zealand Introduction: The magnetic properties of superparamagnetic nanoparticles have been the subject of research for many years. Within the last decade there has been a rapidly growing interest for magnetic nanoparticles motivated by numerous existing and expected applications in biomedicine, like separation of magnetically tagged cells, targeted drug or radionuclide transport into the cells or tissues, contrast improvement in diagnostic MRI and magnetic hyperthermia (local destruction of tumour tissues by inductive heating), amongst many others. The use of magnetic nanoparticles as a drug delivering system is still defined by its biocompatibility and selective targeting to the desired cell or tissue under the guidance of external magnetic field. Advances in current technologies and the development of magnetic nanoparticles as drug delivery systems to deliver drugs to tumor hypoxic zones have fast-tracked in the past decade and led to the development of various magnetic nano-formulations such as liposomes, metallic/nonmetallic, and polymeric nanoparticles. In this study, we have developed superparamagnetic CoFe2O4 nanoparticles for binding to MscL. We show their lack of toxicity on a human cell culture. In addition, we demonstrate the activation of MscL by magnetic field in the presence of the superparamagnetic nanoparticles using patch fluorometry[1]. Materials and Methods: We developed superparamagnetic nanoparticles for activation of the MscL nanovalves by magnetic field. Synthesised CoFe2O4 nanoparticles with the radius less than 10 nm were labelled by SH groups for attachment to MscL. Liposomes made of azolectin (Sigma) were produced using the dehydration/rehydration method as reported previously (Delcour et al. 1989; Häse et al. 1995). Activation of MscL by magnetic field with the nanoparticles attached was examined by the patch clamp technique showing that the number of activated channels under ramp pressure increased upon application of the magnetic field. In addition, we have not observed any cytotoxicity of the nanoparticles in human cultured cells. Nano particles were also characterized by XRD, TEM, FTIR and MPMS. Results and Discussion: By recording the channel activity in patch clamp experiments we found that the number of activated channels increased upon application of the magnetic field in the presence of the nanoparticles, which was not the case in the absence of the magnetic field [Figure 1]. The nanoparticles coated with SH groups on their surface can bind to the cysteine residue of each subunit of the M42C MscL channel mutant by forming a disulphide bond, as previously shown in several EPR and FRET spectroscopic studies. Conclusion: In summary, our study indicates that superparamagnetic nanoparticles of average size of less than 6 nm coated with SH groups are highly suitable as components of a trigger mechanism for opening MscL nanovalves. Due to their very large open pore and property of being modulated by mechanical stimuli MscL channels present an ideal candidate for use as nanovalves in liposomal drug delivery. Consequently, a combination of MscL channels and the magnetic nanoparticles generated for this study holds promise for use in the development of “smart liposomes”, a new generation of liposomal drug delivery system.