Highly Reproducible Hyperthermia Response in Water, Agar, and Cellular Environment by Discretely PEGylated Magnetite Nanoparticles

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Abstract
Local heat generation from magnetic nanoparticles (MNPs) exposed to alternating magnetic fields can revolutionize cancer treatment. However, the application of MNPs as anticancer therapy is limited by serious drawbacks. Foremost among these are the fast uptake and biodegradation of NPs by cancer cells and the unpredictable magnetic behavior of NPs when they accumulate within cells or tissues. In fact, several studies have reported that the heating power of MNPs is severely reduced in the cellular environment, probably due to a combination of increased viscosity and strong NP agglomeration. Herein, we present an optimized protocol to coat magnetite (Fe3O4) NPs larger than 20 nm with high molecular weight PEG molecules that avoid collective coatings, prevent the formation of large clusters of NPs and keep constant their high heating performance in environments with very different ionic strengths and viscosities (distilled water, physiological solutions, agar and cell culture media). The great reproducibility and reliability of the heating capacity of this [email protected] system in such different environments has been confirmed by AC magnetometry and by more conventional calorimetric measurements. The explanation of this behavior has been shown to lie in preserving as much as possible the magnetic single domain-type behavior of nearly isolated NPs. In-vitro endocytosis experiments in colon cancer derived cell line indicate that [email protected] formulations with PEGs of higher molecular weight (20 kDa) are more resistant to endocytosis than formulations with smaller PEGs (5 kDa), showing quite large uptake mean-life ( > 5 h) in comparison with other NP systems. The in-vitro magnetic hyperthermia was performed at 21 mT and 650 kHz during one hour in a pre-endocytosis stage and complete cell death was achieved 48 h post-hyperthermia. These optimal [email protected] formulations with high resistance to endocytosis and predictable magnetic response will aid the progress and the reliability of the emerging era of theranostics.
Funding Information
  • H2020 Marie Sklodowska-Curie Actions (798830)
  • Eusko Jaurlaritza (GU_IT1226-19)

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