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.
Dextran stabilized La(0.7)Sr(0.3)MnO(3) (Dex-LSMO) is an alternative cancer hyperthermia agent holding considerable promise. Here, we have carried out a comparative study on radio frequency (~264 kHz) induced Dex-LSMO mediated heating and extraneous heating (mimicking generalized hyperthermia) in terms of changes in the morphology, proliferation pattern and induction of heat shock proteins in a human melanoma cell line (A375). Our results clearly show that the cellular effects seen with extraneous heating (60 min at 43 °C) could be reproduced by just six minutes of radio frequency induced Dex-LSMO mediated heating. More importantly, the observed enhanced levels of HSP 70 and 90 (molecular markers of heat shock that trigger favorable immunological reactions) seen with Dex-LSMO mediated heating were comparable to extraneous heating. These results suggest the possible utility of Dex-LSMO as a cancer hyperthermia agent.
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