RESUMO
Increasing effectiveness of cancer therapeutics requires a multipronged approach. Delivery of controlled hyperthermia in the ranges of 43 to 45 °C on site aided by superparamagnetic particles ensures cell death via the apoptosis pathway.We demonstrated the use of iron-oxide embedded hydroxyapatite (HAIO) superparamagnetic particles for delivery of controlled hyperthermia and contrast enhancement in MRI. To determine optimal hyperthermia delivery, we used 5 and 10 mg/mL concentrations of HAIO on various magnetic fields in alternating magnetic field (AMF) study. Time-temperature profile and specific loss power (SLP) data revealed that HAIO delivered precisely controlled temperature in contrast to superparamagnetic iron oxide nanoparticles (SPIONs). Earlier studies had demonstrated that HAIO concentrations of 0.5 to 3 mg/mL are cytocompatible. Exposure of HeLa cells to HAIO at a concentration of 2 mg/mL and applied field of 33.8 mT for a period of 30 min resulted in apoptosis induction in 75% of population. Significant cellular disruption was affirmed via FACS, ESEM and cLSM techniques. An aqueous phantom study and in vitro cell culture study evaluation indicated relaxivity of 50.92 mM-1 s-1 and good pixel intensity variation in MRI. The current study assesses the potential of HAIO to deliver controlled hyperthermia and act as a negative MRI contrast agent. Repeated experiments have confirmed enhanced utility of the technique in the burgeoning field of theranostics.
RESUMO
Despite the success in the use of superparamagnetic iron oxide nanoparticles (SPION) for various scientific applications, its potential in biomedical fields has not been exploited to its full potential. In this context, an in situ substitution of Mn(2+) was performed in SPION and a series of ferrite particles, MnxFe1-xFe2O4 with a varying molar ratio of Mn(2+) : Fe(2+) where 'x' varies from 0-0.75. The ferrite particles obtained were further studied in MRI contrast applications and showed appreciable enhancement in their MRI contrast properties. Manganese substituted ferrite nanocrystals (MnIOs) were synthesized using a novel, one-step aqueous co-precipitation method based on the use of a combination of sodium hydroxide and trisodium citrate (TSC). This approach yielded the formation of highly crystalline, superparamagnetic MnIOs with good control over their size and bivalent Mn ion crystal substitution. The presence of a TSC hydrophilic layer on the surface facilitated easy dispersion of the materials in an aqueous media. Primary characterizations such as structural, chemical and magnetic properties demonstrated the successful formation of manganese substituted ferrite. More significantly, the MRI relaxivity of the MnIOs improved fourfold when compared to SPION crystals imparting high potential for use as an MRI contrast agent. Further, the cytocompatibility and blood compatibility evaluations demonstrated excellent cell morphological integrity even at high concentrations of nanoparticles supporting the non-toxic nature of nanoparticles. These results open new horizons for the design of biocompatible water dispersible ferrite nanoparticles with good relaxivity properties via a versatile and easily scalable co-precipitation route.
