As heat or ‘hyperthermia’ sensitizes living cells to apoptotic stimuli, this unique feature of SPIONs appears specifically beneficial in cancer therapy where temperatures learn more between 40°C and 45°C have been demonstrated to synergistically

enhance or potentiate chemotherapy and radiation efficacy [11, 12]. Hyperthermia generated by SPIONs following exposure to an alternating magnetic field arises from energy loss associated with oscillation and Néel/Brownian relaxation of the nanoparticle magnetic moment [13]. Stimulus-induced heat generation can also be utilized to control dissociation of a therapeutic moiety from a thermoresponsive carrier that undergoes reversible volume or sol-gel phase selleckchem transition within a desired range of 37°C to 45°C [14–16]. Previously, our laboratory described a novel phospholipid/Fe3O4 nanocomposite designed for stimulus-controlled release of an encapsulated PD-1/PD-L1 inhibitor payload via magnetically

induced hyperthermia [12]. These results demonstrated the feasibility of immobilizing a 2- to 3-nm-thick layer of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) on the surface of SPIONs via high affinity avidin/biotin interactions without negatively affecting magnetically induced heating properties. However, moderate surface charge (zeta potential -5.0 ± 3.0 mV) afforded by the zwitterionic but charge-neutral phospholipid assembly resulted in limited colloidal stability, which rapidly led to particle aggregation into the micrometer range [12]. The aim of the present study was to explore the impact of a modified phospholipid

composition and different fabrication parameters during the lipid coating process on colloidal stability of these thermoresponsive nanocomposites. In addition, the concentration-dependent heating behavior of these nanoassemblies was compared using two magnetic field generators of different designs. Surface immobilization of an equimolar mixture of DPPC and l-α-dipalmitoylphosphatidyl glycerol (DPPG) on SPIONs significantly increased colloidal stability of these nanocomposites in physiological buffer systems. Exposure to an alternating magnetic field rapidly increased (-)-p-Bromotetramisole Oxalate the temperature of the surrounding vehicle as a consequence of magnetically induced hyperthermia. Heating rates were dependent on particle concentration, suspension vehicle, and magnetic field generator design. These results underline the importance of standardized in vitro assessment of SPIONs for magnetically induced hyperthermia applications in order to effectively facilitate clinical development of these promising nanocarriers. Methods Fe3O4 nanoparticles SPIONs were synthesized following a previously published coprecipitation method [17]. Briefly, 4.44 g of FeCl3·6H2O and 1.73 g of FeCl2·4H2O (Thermo-Fischer Scientific, Pittsburgh, PA, USA) were dissolved in deionized water at a molar ratio of 1:2. Temperature was increased to 70°C while stirring under N2 protection before 20 mL of an aqueous 0.