Preparation and characterization of temperature-responsive magnetite nanoparticles conjugated with N-isopropylacrylamide-based functional copolymer
Introduction
Until recently, magnetite nanoparticles were typically used as ferrofluids and only lately much attention has been directed to their biomedical applications [1], [2], especially as targeting drug delivery devices [3], [4], [5]. Nano-sized magnetite nanoparticles dispersed with water-soluble dextran or incorporated in liposome were designed for delivery by induction with extracorporeal magnet movement. Moreover, it is well known that the nanoparticles can effectively provide a source of heat induced by an alternating magnetic field. Therefore, the nanoparticles were used as localized heating mediator agents for hyperthermia [6], [7]. Furthermore, based on the magnetic attractive force and large surface area available for chemical binding, the magnetite particles have been applied to cell separations [8], [9], magnetic resonance imaging (MRI) [10], [11], enzyme and protein immobilization [12], [13], [14], immunoassays [15], and RNA and DNA purification [16], [17], [18]. To develop the functional nano-sized magnetite particles, a stable dispersion in organic or aqueous media is critical for the successful modification with organic compounds or polymers.
Poly(N-isopropylacrylamide) (PIPAAm) is one of the thermo-responsive polymers that produces a coil-to-globule transition around the lower critical solution temperature (LCST). This phenomenon is based on a reversible hydration–dehydration of amide groups in the molecules [19], [20]. At a temperature lower than the LCST, the polymer is completely soluble in aqueous media. However, on the other hand, with the increasing temperature, the polymer solution becomes opaque and precipites over the LCST. For example, the modification using this polymer is very useful to fabricate an enzyme whose solubility is controlled by only temperature change [21]. Such a phase transition occurs in a narrow temperature range; therefore, the modification of PIPAAm would improve the stability and produce a sensitive temperature-dependent property. From this point of view, Kondo et al. reported thermo-responsive magnetite nanoparticles using N-isopropylacrylamide (NIPAAm)-based copolymer [22]. The conjugated nanoparticles that they prepared have the advantage of easy separation and recovery of proteins by the synergism of magnetic force and hydrophobic interaction. According to their paper, for the preparation of the NIPAAm copolymer to bind bioactive molecules, methacrylic acid was used.
We have succeeded in preparing NIPAAm-based copolymers with both sensitive temperature-response and chemical reactivity. To achieve this, 2-carboxyisopropylacrylamide (CIPAAm) and 2(benzyloxycarbonyl)aminoisopropylacrylamide (Z-protected AIPAAm) were designed to include the chemical structure of comonomer alignment in the copolymers [23], [24], [25]. These copolymers comprise completely random sequences of comonomers due to the almost same reactivity ratios; therefore, they would contribute to the sensitive temperature-response and uniform immobilization of the molecules. Furthermore, the combination of these NIPAAm-based reactive copolymers with magnetite nanoparticles could lead to a temperature-responsive drug carrier system, because the magnetite would provide a source of heat in the magnetic field.
Section snippets
Materials
The magnetite nanoparticles were kindly supplied by Toda Kogyo Corp. (Hiroshima, Japan). The nanoparticles were spherical and had an average particle size of approximately 130 nm.These characteristics of the polymer-conjugated particles were confirmed by transmission electron microscopy (TEM, N-700H, HITACHI, Tokyo, Japan) and X-ray diffraction (XRD) measurements (RINT 2200 HK/PC, RIGAKU, Tokyo, Japan). 3-aminopropyltrimethoxysilane (APTMS) was obtained from the Shin-etsu Co. (Tokyo, Japan) and
Immobilization of temperature-responsive polymers
It is well known that metal oxides, such as Fe3O4, react with a silane coupling agent and the desired functional groups can be thus introduced onto the surface [26], [27], [28]. In this study, to immobilize the temperature-responsive IPAAm-based functional copolymer onto magnetite nanoparticle surfaces, APTMS was used to achieve a stable amide bond formation with amino groups. Fig. 1 shows XPS spectra of the reacted magnetite nanoparticle surfaces in which peaks corresponding to the N and Si
Conclusions
We succeeded in the preparation of magnetite nanoparticles conjugated with a temperature-responsive PIPAAm-based functional polymer. The polymer was derived from the copolymerization of IPAAm and CIPAAm. This nanoparticle system showed a sensitive and reversible hydrophilic–hydrophobic change in response to the heat induced by the AC magnetic field. These temperature-responsive magnetite nanoparticles contain carboxyl groups, and these groups can be used as the binding point of the drug.
We are
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