In this letter, we report a new, one-step, rapid, and easy-to-implement method for the synthesis of PEGylated gold nanoparticles (PEG-AuNPs) having a narrow size distribution and very interesting plasmonic properties. Unmodified polyethylene glycol molecules with a molecular weight of 1000 g/mole (PEG1000) have been employed as reducing and capping agents for the synthesis of spherical gold nanoparticles having an average diameter of 35 nm, within a few minutes. The novelty of the herein proposed synthesis method consists in the fact that the synthesis takes place inside of a sealed bottle flask containing aqueous solutions of PEG1000, tetrachloroauric(III) acid (HAuCl4), and NaOH, placed in the center of a microwave oven, capable to provide a very uniform temperature environment. It turned out that, during the very short synthesis procedure (2 minutes), PEG 1000 suffers an oxidative transformation in such a manner that its terminal alcohol groups (-CH2-OH) are transformed in carboxylate ones (-COO−). The as-synthesized PEG-AuNPs possess very interesting plasmonic properties allowing the detection of different molecules by means of SER spectroscopy performed either in liquid droplets or on solid spots. As a consequence of their unique plasmonic properties, the SER spectra acquired using this new class of nanoparticles on different molecules of interest (methylene blue, rhodamine 6G, doxorubicin, and 5-fluorouracil) are highly reproducible, making them ideal candidates for further use as SERS substrates.

Increasing the biocompatibility, cellular uptake, and magnetic heating performance of ferromagnetic iron-oxide magnetic nanoparticles (F-MNPs) is clearly required to efficiently induce apoptosis of cancer cells by magnetic hyperthermia (MH). Thus, F-MNPs were coated with silica layers of different thicknesses via a reverse microemulsion method, and their morphological, structural, and magnetic properties were evaluated by multiple techniques. The presence of a SiO2 layer significantly increased the colloidal stability of F-MNPs, which also enhanced their heating performance in water with almost 1000 W/gFe as compared to bare F-MNPs. The silica-coated F-MNPs exhibited biocompatibility of up to 250 μg/cm2 as assessed by Alamar Blues and Neutral Red assays on two cancer cell lines and one normal cell line. The cancer cells were found to internalize a higher quantity of silica-coated F-MNPs, in large endosomes, dispersed in the cytoplasm or inside lysosomes, and hence were more sensitive to in vitro MH treatment compared to the normal ones. Cellular death of more than 50% of the malignant cells was reached starting at a dose of 31.25 μg/cm2 and an amplitude of alternating magnetic field of 30 kA/m at 355 kHz.

The applications of ferrimagnetic nanoparticles (F-MNPs) in magnetic hyperthermia (MH) are restricted by their stabilization in microscale aggregates due to magnetostatic interactions significantly reducing their heating performances. Coating the F-MNPs in a silica layer is expected to significantly reduce the magnetostatic interactions, thereby increasing their heating ability. A new fast, facile, and eco-friendly oil-in-water microemulsion-based method was used for coating Zn0.4Fe2.6O4 F-MNPs in a silica layer within 30 min by using ultrasounds. The silica-coated clusters were characterized by various physicochemical techniques and MH, while cytotoxicity studies, cellular uptake determination, and in vitro MH experiments were performed on normal and malignant cell lines. The average hydrodynamic diameter of silica-coated clusters was approximately 145 nm, displaying a high heating performance (up to 2600 W/gFe). Biocompatibility up to 250 μg/cm2 (0.8 mg/mL) was recorded by Alamar Blue and Neutral Red assays. The silica-coating increases the cellular uptake of Zn0.4Fe2.6O4 clusters up to three times and significantly improves their intracellular MH performances. A 90% drop in cellular viability was recorded after 30 min of MH treatment (20 kA/m, 355 kHz) for a dosage level of 62.5 μg/cm2 (0.2 mg/mL), while normal cells were more resilient to MH treatment.

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The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report a simple, rapid, and reproducible method for the preparation of thermosensitive magnetoliposomes (TsMLs) loaded with doxorubicin (DOX), consisting of a lipidic gel formation from a previously obtained water-in-oil microemulsion with fine aqueous droplets containing magnetic nanoparticles (MNPs) dispersed in an organic solution of thermosensitive lipids (transition temperature of ~43 °C), followed by the gel hydration with an aqueous solution of DOX. The obtained thermosensitive magnetoliposomes (TsMLs) were around 300 nm in diameter and exhibited 40% DOX incorporation efficiency. The most suitable MNPs to incorporate into the liposomal aqueous lumen were Zn ferrites, with a very low coercive field at 300 K (7 kA/m) close to the superparamagnetic regime, exhibiting a maximum absorption rate (SAR) of 1130 W/gFe when dispersed in water and 635 W/gFe when confined inside TsMLs. No toxicity of Zn ferrite MNPs or of TsMLs was noticed against the A459 cancer cell line after 48 h incubation over the tested concentration range. The passive release of DOX from the TsMLs after 48h incubation induced a toxicity starting with a dosage level of 62.5 ug/cm2. Below this threshold, the subsequent exposure to an alternating magnetic field (20–30 kA/m, 355 kHz) for 30 min drastically reduced the viability of the A459 cells due to the release of incorporated DOX. Our results strongly suggest that TsMLs represent a viable strategy for anticancer therapies using the magnetic field-controlled release of DOX.

By carefully controlling the electrostatic interactions between cationic liposomes, which already incorporate magnetic nanoparticles in the bilayers, and anionic gold nanoparticles, a new class of versatile multifunctional nanohybrids (plasmonic magneto-liposomes) that could have a major impact in drug delivery and controlled release applications has been synthesized. The experimental results confirmed the successful synthesis of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and polyethylene glycol functionalized (PEGylated) gold nanoparticles (AuNPs). The SPIONs were incorporated in the liposomal lipidic bilayers, thus promoting the formation of cationic magnetoliposomes. Different concentrations of SPIONs were loaded in the membrane. The cationic magnetoliposomes were decorated with anionic PEGylated gold nanoparticles using electrostatic interactions. The successful incorporation of SPIONs together with the modifications they generate in the bilayer were analyzed using Raman spectroscopy. The plasmonic properties of the multifunctional nanohybrids were investigated using UV-Vis absorption and (surface-enhanced) Raman spectroscopy. Their hyperthermic properties were recorded at different frequencies and magnetic field intensities. After the synthesis, the nanosystems were extensively characterized in order to properly evaluate their potential use in drug delivery applications and controlled release as a result of the interaction with an external stimulus, such as an NIR laser or alternating magnetic field.

The collective organization of magnetic nanoparticles (MNPs) influences significantly their hyperthermic properties, relevant for their in vitro and in vivo applications. We report a systematic investigation of the effects of the concentration and the static bias direct current (DC) magnetic field superposed over the alternating magnetic field (AMF), both in a parallel and perpendicular configuration, on the specific absorption rate (SAR) by using zinc ferrite MNPs. The nonmonotonic dependence of the SAR on the concentration, with a maximum at very small concentrations (c ≤ 0.1 mgFe/mL), followed by a minimum at 0.25 mgFe/mL, and the second maximum of 3.3 kW/gFe at around 1 mgFe/mL, was explained by the passage of the MNPs from a single particle behavior to a collective one and the role of the dipolar interactions. By superposing a static 10 kA/m bias DC field on the AMF we obtained an increase in the SAR for both parallel and perpendicular orientations, up to 4285 W/gFe and 4070 W/gFe, respectively. To the best of our knowledge, this is the first experimental proof of a significant enhancement of the SAR produced by a perpendicular DC field. The effect of the DC field to increase the SAR is accompanied by an increase in the hyperthermia coercive field (HcHyp) for both configurations. No enhancement of the DC fields was noticed for the MNPs immobilized in a solid matrix but the DC field increases the HcHyp only in the parallel configuration. This translates into a higher SAR value for the perpendicular configuration as compared to the parallel configuration. These results have practical applications for magnetic hyperthermia.