Poly(2-oxazoline)-magnetite NanoFerrogels: Magnetic field responsive theranostic platform for cancer drug delivery and imaging.

Combining diagnosis and treatment approaches in one entity is the goal of theranostics for cancer therapy. Magnetic nanoparticles have been extensively used as contrast agents for nuclear magnetic resonance imaging as well as drug carriers and remote actuation agents. Poly(2-oxazoline)-based polymeric micelles, which have been shown to efficiently solubilize hydrophobic drugs and drug combinations, have high loading capacity (above 40% w/w) for paclitaxel. In this study, we report the development of novel theranostic system, NanoFerrogels, which is designed to capitalize on the magnetic nanoparticle properties as imaging agents and the poly(2-oxazoline)-based micelles as drug loading compartment. We developed six formulations with magnetic nanoparticle content of 0.3%-12% (w/w), with the z-average sizes of 85-130 nm and ξ-potential of 2.7-28.3 mV. The release profiles of paclitaxel from NanoFerrogels were notably dependent on the degree of dopamine grafting on poly(2-oxazoline)-based micelles. Paclitaxel loaded NanoFerrogels showed efficacy against three breast cancer lines which was comparable to free paclitaxel. They also showed improved tumor and lymph node accumulation and signal reduction in vivo (2.7% in tumor; 8.5% in lymph node) compared to clinically approved imaging agent ferumoxytol (FERAHEME®) 24 h after administration. NanoFerrogels responded to super-low frequency alternating current magnetic field (50 kA m-1, 50 Hz) which accelerated drug release from paclitaxel-loaded NanoFerrogels or caused death of cells loaded with NanoFerrogels. These proof-of-concept experiments demonstrate that NanoFerrogels have potential as remotely actuated theranostic platform for cancer diagnosis and treatment.

Dynamic characterization of indocyanine green-assisted dental caries ablation with continuous diode laser using thermal imaging and fluorescence spectroscopy.

We describe the time-resolved thermal changes in indocyanine green (ICG)-assisted diode laser ablation of dental caries as a potential technique for painless treatment based on the selective photoabsorption and controlled photothermal ablation. Static ablation mode produced a higher temperature rise compared with scanning mode due to localized accumulation of heat. A temperature rise between 45-80 and 70-95 °C was obtained after 20 s that corresponded to 29 and 80 W cm-2, respectively. The temperature of the tooth surface increased by irradiation time, and it behaved linearly up to 70 °C at 29 and 80 W cm-2. A maximum ablation per area of about 0.3 and 0.45 mg cm-2 was achieved after 80 s exposure at 29 and 80 W cm-2, respectively. A statistically significant difference is observed in mean carious teeth weight at various exposure times between low and high irradiances. A thermal penetration depth of 0.8-9 mm is determined for 1-100 s of exposure time. The IR thermal imaging of ICG temperature as a function of exposure time showed a linear increase for 60 s beyond which it deviated. The laser-induced fluorescence spectroscopy indicated that the ICG quality can be altered during the course of irradiation, which in our case, it corresponded to ≈ 78% loss of signal within 23 min of exposure. The caries removal experiment was performed within 100 s corresponding to ≈ 7% loss. We believe that the application of the above-combined technique can be utilized as a monitoring device to control the ablation interaction process.

Medical application of biomimetic 4D printing.

Additive manufacturing has attracted a lot of attention in fabrication of bio medical devices and structures in recent years. 4D printing, a new class of 3D printing where time is considered as a 4th dimension, allows us to build biological structures such as scaffolds, implants, and stents with dynamic performance mimicking the body's natural tissues. In order to properly exploit the capabilities of this fabrication method, understanding and exploiting the shape memory materials is critical. These 'smart' materials are responsive to the external stimuli which eliminates the need for utilizing the sensors, and batteries. These stimuli-triggered 'smart' materials possess a dynamic behavior unlike the static scaffolds based on conventional manufacturing techniques. In this review, recent advances on application of 4D printing for manufacturing of this type of materials and other high-performance biomaterials for medical applications have been discussed.

Enhanced cellular uptake of size-separated lipophilic silicon nanoparticles.

Specific size, shape and surface chemistry influence the biological activity of nanoparticles. In the case of lipophilic nanoparticles, which are widely used in consumer products, there is evidence that particle size and formulation influences skin permeability and that lipophilic particles smaller than 6 nm can embed in lipid bilayers. Since most nanoparticle synthetic procedures result in mixtures of different particles, post-synthetic purification promises to provide insights into nanostructure-function relationships. Here we used size-selective precipitation to separate lipophilic allyl-benzyl-capped silicon nanoparticles into monodisperse fractions within the range of 1 nm to 5 nm. We measured liposomal encapsulation and cellular uptake of the monodisperse particles and found them to have generally low cytotoxicities in Hela cells. However, specific fractions showed reproducibly higher cytotoxicity than other fractions as well as the unseparated ensemble. Measurements indicate that the cytotoxicity mechanism involves oxidative stress and the differential cytotoxicity is due to enhanced cellular uptake by specific fractions. The results indicate that specific particles, with enhanced suitability for incorporation into lipophilic regions of liposomes and subsequent in vitro delivery to cells, are enriched in certain fractions.

Screening of Lipid Composition for Scalable Fabrication of Solvent-Free Lipid Microarrays.

Liquid microdroplet arrays on surfaces are a promising approach to the miniaturization of laboratory processes such as high-throughput screening. The fluid nature of these droplets poses unique challenges and opportunities in their fabrication and application, particularly for the scalable integration of multiple materials over large areas and immersion into cell culture solution. Here, we use pin spotting and nanointaglio printing to screen a library of lipids and their mixtures for their compatibility with these fabrication processes, as well as stability upon immersion into aqueous solution. More than 200 combinations of natural and synthetic oils composed of fatty acids, triglycerides, and hydrocarbons were tested for their pin-spotting and nanointaglio print quality and their ability to contain the fluorescent compound tetramethylrhodamine B isothiocyanate (TRITC) upon immersion in water. A combination of castor oil and hexanoic acid at the ratio of 1:1 (w/w) was found optimal for producing reproducible patterns that are stable upon immersion into water. This method is capable of large-scale nanomaterials integration.

Simulation and experimental results of optical and thermal modeling of gold nanoshells.

This paper proposes a generalized method for optical and thermal modeling of synthesized magneto-optical nanoshells (MNSs) for biomedical applications. Superparamagnetic magnetite nanoparticles with diameter of 9.5 ± 1.4 nm are fabricated using co-precipitation method and subsequently covered by a thin layer of gold to obtain 15.8 ± 3.5 nm MNSs. In this paper, simulations and detailed analysis are carried out for different nanoshell geometry to achieve a maximum heat power. Structural, magnetic and optical properties of MNSs are assessed using vibrating sample magnetometer (VSM), X-ray diffraction (XRD), UV-VIS spectrophotometer, dynamic light scattering (DLS), and transmission electron microscope (TEM). Magnetic saturation of synthesized magnetite nanoparticles are reduced from 46.94 to 11.98 emu/g after coating with gold. The performance of the proposed optical-thermal modeling technique is verified by simulation and experimental results.