Protein and polymer immobilized La_0.7Sr_0.3MnO₃nanoparticles for possible biomedical applications

Abstract

La0.7Sr0.3MnO3 (LSMO) is a mixed-valent room temperature ferromagnet with properties that are attractive for their applicability in biomedicine. We report, for the first time, immobilization of commonly used biocompatible molecules on LSMO nanoparticles, namely bovine serum albumin and dextran. The former was conjugated to LSMO using 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide (CDI) as a coupling agent while the latter was used without any coupler. These bioconjugated nanoparticles exhibit several properties that suggest their applicability in the field of biomedicine, namely (a) no changes in the Curie temperature at ∼360 K after conjugation with biomolecules, (b) rapid attainment of the desired temperature (48 °C) at low concentration (e.g. fluidized dextran-coated system at 80 µg ml−1) upon exposure to 20 MHz radio-frequency, (c) extremely low cytotoxicity in skin carcinoma, human fibrosarcoma and neuroblastoma cell lines and (d) high stability of the LSMO system with negligible leaching of ionic manganese into the delivery medium, indicating their safety in possible human applications.

Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3: in vitro studies

“…We therefore evaluated the cytotoxicity of Dex-LSMO nanoparticles alone in various cell lines. As reported elsewhere, 21,23 we have noted a cell line-dependent and concentration-dependent cytotoxic effect of Dex-LSMO nanoparticles. Nevertheless, coating of LSMO with dextran could significantly reduce cytotoxicity as compared with bare LSMO.…”

“…21 These dextran-coated (Dex)-LSMO nanoparticles were found to display a low Curie temperature (360 K) and self-controlled heating properties on exposure to RF. 22,23 To evaluate the efficacy of hyperthermia mediated by Dex-LSMO nanoparticles, we selected murine melanoma (B16F1) cells as a cancer model, since this cancer is reported to be resistant to conventional treatment such as chemotherapy. 24 Before treatment with hyperthermia, it was important to confirm that the Dex-LSMO nanoparticles themselves do not damage cells.…”

“…Nevertheless, coating of LSMO with dextran could significantly reduce cytotoxicity as compared with bare LSMO. 21,23,25 Based on our previous research, a Dex-LSMO concentration of 250 μg/mL was found to be safe in melanoma cells and therefore was used in further experiments. 25 The results of an internalization study was performed using fluorescence microscopy to investigate intracellular localization of nanoparticles.…”

“…23 Briefly, presynthesized LSMO nanoparticles (200 mg) were dispersed in 10 mL of double-distilled water and bath-sonicated for 30 minutes. An equal concentration of dextran sulfate was added to the dispersion of LSMO nanoparticles and sonicated for another 30 minutes.…”

Hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3 nanoparticles: in vivo studies

“…We have earlier reported that dextran-coated La 0.7 Sr 0.3 MnO 3 (Dex-LSMO) nanoparticles (30-50 nm) with Curie temperature of ~360 K (~86°C) show self-controlled heating property and have potential to be used for both localized hyperthermia 13,14 and magnetic resonance imaging (MRI). 15 Although iron oxide nanoparticles (magnetite/maghemite) are extensively studied for hyperthermia, the heating is not self-controlled in the therapeutic range owing to their high Curie temperature.…”