Alternating Magnetic Field Controlled, Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility

Abstract

Biocompatible magnetic nanoparticles hold great therapeutic potential, but conventional particles can be toxic. Here, we report the synthesis and alternating magnetic field dependent actuation of a remotely controllable, multifunctional nano-scale system and its marked biocompatibility with mammalian cells. Monodisperse, magnetic nanospheres based on thermo-sensitive polymer network poly(ethylene glycol) ethyl ether methacrylate-co-poly(ethylene glycol) methyl ether methacrylate were synthesized using free radical polymerization. Synthesized nanospheres have oscillating magnetic field induced thermo-reversible behavior; exhibiting desirable characteristics comparable to the widely used poly-N-isopropylacrylamide-based systems in shrinkage plus a broader volumetric transition range. Remote heating and model drug release were characterized for different field strengths. Nanospheres containing nanoparticles up to an iron concentration of 6 mM were readily taken up by neuron-like PC12 pheochromocytoma cells and had reduced toxicity compared to other surface modified magnetic nanocarriers. Furthermore, nanosphere exposure did not inhibit the extension of cellular processes (neurite outgrowth) even at high iron concentrations (6 mM), indicating minimal negative effects in cellular systems. Excellent intracellular uptake and enhanced biocompatibility coupled with the lack of deleterious effects on neurite outgrowth and prior Food and Drug Administration (FDA) approval of PEG-based carriers suggest increased therapeutic potential of this system for manipulating axon regeneration following nervous system injury.

Novel antifouling oligo(ethylene glycol) methacrylate particles via surfactant-free emulsion polymerization

“…Poly(ethylene glycol) ethyl ether methacrylate (PEGEEM) is a macromonomer with three ethylene glycol units and is used widely in the literature as a surface modifier for particle systems [9,10], a thermosensitive polymer [11][12][13] as well as a stabilizing co-monomer in surfactant-free emulsion polymerization (SFEP) [14][15][16][17]. For instance, magnetic nanoparticles with a surface PEGEEM modification showed excellent cellular uptake and biocompatibility [9], and the incorporation of PEGEEM onto starshaped cationic nonviral gene vectors reduced cytotoxicity and enhanced gene transfection efficiency [10].…”

“…For instance, magnetic nanoparticles with a surface PEGEEM modification showed excellent cellular uptake and biocompatibility [9], and the incorporation of PEGEEM onto starshaped cationic nonviral gene vectors reduced cytotoxicity and enhanced gene transfection efficiency [10]. The thermoresponsive behavior of oligo(ethylene glycol) methacrylates was extensively demonstrated by Lutz and coworkers who proposed the use of these monomers in smart biomaterial production [13].…”

Synthesis and characterization of a novel thermoresponsive copolymer series and their application in cell and cell sheet regeneration

“…The major obstacle to using pNIPAm coatings for this desired outcome is that pNIPAm coatings tend to be poorly cell compatible, with cells resisting attaching to bare pNIPAm surfaces [9][10][11][12]. Efforts to overcome this lack of compatibility have involved the copolymerization of the NIPAm monomer with another suitably chosen monomer to attain a more biocompatible copolymer or by adding an over-layer of cell adhesion encouraging proteins to a pNIPAm coating [1,10,13].…”

“…Efforts to overcome this lack of compatibility have involved the copolymerization of the NIPAm monomer with another suitably chosen monomer to attain a more biocompatible copolymer or by adding an over-layer of cell adhesion encouraging proteins to a pNIPAm coating [1,10,13]. An alternative approach has been taken by Okano et al whereby an ultra thin coating of pNIPAm is deposited using the complex electron beam polymerization technique [14].…”

Evaluation of the Biological Effects of Externally Tunable, Hydrogel Encapsulated Quantum Dot Nanospheres in Escherichia coli

“…Recently, QDs are being used extensively for labeling [1][2][3][4][5][6][7][8] in biomedical research due to their unique photoluminescence properties: (1) size-tunable emission color, (2) a narrow and symmetric emission profile and (3) a broad excitation range. At the same time, based on excellent biological compatibility, adaptability to pH and temperature changes, as well as responsiveness to magnetic or electric fields, hydrogel nanospheres have become suitable carriers for drugs, fluorescent labels, magnetic particles for hyperthermia applications, and particles that have strong absorption profiles for optical excitation [7,[9][10][11][12]. Therefore, integration of fluorescent, water-soluble QDs into hydrogel nanospheres provides a new generation of fluorescence markers for biological assays.…”