Magnetic iron oxide nanoparticles as long wavelength photoinitiators for free radical polymerization

Iron oxide nanoparticles (Fe3O4 NPs) capped with lauric acid agents were synthesized and their photocatalytic activity was investigated in free radical photopolymerization of vinyl monomers. These NPs were able to release charge carriers (electron-hole pairs) upon photoexcitation through which the capping agents or an additional amine co-initiator acting as the hole acceptor underwent oxidation to eventually form the initiating radicals. In lauric acid coated Fe3O4 NPs, electron transfer followed by a decarboxylation process accounts for the initiation

RGDS-functionalized polyethylene glycol hydrogel-coated magnetic iron oxide nanoparticles enhance specific intracellular uptake by HeLa cells

The objective of this study was to develop thin, biocompatible, and biofunctional hydrogel-coated small-sized nanoparticles that exhibit favorable stability, viability, and specific cellular uptake. This article reports the coating of magnetic iron oxide nanoparticles (MIONPs) with covalently cross-linked biofunctional polyethylene glycol (PEG) hydrogel. Silanized MIONPs were derivatized with eosin Y, and the covalently cross-linked biofunctional PEG hydrogel coating was achieved via surface-initiated photopolymerization of PEG diacrylate in aqueous solution. The thickness of the PEG hydrogel coating, between 23 and 126 nm, was tuned with laser exposure time. PEG hydrogel-coated MIONPs were further functionalized with the fibronectin-derived arginine-glycine-aspartic acid-serine (RGDS) sequence, in order to achieve a biofunctional PEG hydrogel layer around the nanoparticles. RGDS-bound PEG hydrogel-coated MIONPs showed a 17-fold higher uptake by the human cervical cancer HeLa cell line than that of amine-coated MIONPs. This novel method allows for the coating of MIONPs with nano-thin biofunctional hydrogel layers that may prevent undesirable cell and protein adhesion and may allow for cellular uptake in target tissues in a specific manner. These findings indicate that the further biofunctional PEG hydrogel coating of MIONPs is a promising platform for enhanced specific cell targeting in biomedical imaging and cancer therapy

Development of theranostic PNIPAM/SPION nanoparticles for cancer treatment

Backround/Aim: Stimuli-responsive nanoparticles are being investigated for controlled delivery of toxic drugs to the disease site, especially in cancer. Tumors are known as more acidic and hypertermic in comparison with healthy body parts. Thus, pH and/or temperature-responsive drug delivery vehicles have a tremendous importance in achieving secure delivery and se-cretion of the cargo chemotherapeutic drug only to the tumor site to enhance the efficacy and reduce side effects. Materi-als & Methods: In this study, Poly (N-isopropylacrylamide) (PNIPAM) bound Fe3O4 nanoparticles (SPION-PNIPAM) were synthesized via surface initiated ATRP (atom transfer radical polymerization) and loaded with chemotherapeutic drug Doxo-rubicin (Dox). We performed MTT and Trypan Blue Exclusion Assay to evaluate dose and temperature dependent cell viabili-ty exposed to Dox, nanoparticles and Dox loaded nanoparticles. Confocal analysis was carried out to observe cellular uptake and intracellular trafficking of NPs. Gamma-H2AX phosphor-ylation, p53 and Caspase activation were examined through Immunoblotting to identify the NP and drug dependent DNA damage in vitro. Results: Release studies performed at differ-ent temperatures (25 °C, 37 °C, 42 °C) and pH (7.4, 5.6) re-vealed both pH and temperature dependent release which is minimal at physiological pH and temperature and maximum at low pH-high temperature combination. For the toxicity studies, we have used HeLa cervical cancer cells. Administration of the PNIPAM/SPION alone did not show toxic effect event at high doses, proving safety of the delivery vehicle.. However, Dox loaded NPs (0.3 μg/ml and 1.3 μg/ml drug content) showed dose and time dependent toxicity. Based on the confocal microsco-py studies, internalization of NPs increases with the NP dose, incubation time and temperature. We have also observed that NPs were internalized through endosomal pathway using the endosomal markers Rab5 and Rab9. In addition, cells incubated with Dox loaded NPs exhibited higher levels of gamma-H2AX phosphorylation, p53 and Caspase activation in comparison to free Doxorubicin. Conclusion: According to our findings, du-ally responsive controlled drug release behavior makes these SPION-PNIPAM nanoparticles valuable stimuli responsive theranostic candidates

Development of tailored SPION-PNIPAM nanoparticles by ATRP for dually responsive doxorubicin delivery and MR imaging

Biocompatible, colloidally stable and ultra-small Fe3O4 nanoparticles (SPIONs) coated with poly(N-isopropyl-acrylamide) (PNIPAM) were synthesized via surface-initiated ATRP (atom transfer radical polymerization) to prevent excessive aggregation of magnetic cores and interparticle crosslinking, and to provide control over polymer content. These SPION-PNIPAM nanoparticles (NPs) have a hydrodynamic size between 8 and 60 nm depending on the PNIPAM content, and hence are ultrasmall in size and have an LCST around 38 degrees C. They had a high drug-loading capacity reaching 9.6 wt% doxorubicin in the final composition. The Dox release studies revealed pH and temperature-dependent release, which was not reported for PNIPAM before. Release of Dox under physiological conditions was below 20%, but around 90% at 42 degrees C and pH 5. This dually responsive nature is very advantageous to increase the drug efficacy and reduce side-effects, simultaneously. The cytocompatability of the SPION-PNIPAM NPs and the influence of Dox delivery to cells were investigated via in vitro cell viability, apoptosis, DNA-damage and confocal microscopy studies. The NPs were shown to be highly cytocompatible and induce significant cell death due to Dox when loaded with the drug. Besides, it was seen that the polymeric content can be used as an additional factor in tuning the release kinetics. Lastly, these nanoparticles reduced the signal intensity significantly in the T2 mode, acting as a potential SPION-based contrast agent. Overall, here, we demonstrate the design of small, smart theranostic nanoparticles with high drug-loading capacity and pH-dependent temperature-sensitive release characteristics with the ability to generate contrast in MRI