Liposome Formulation for Tumor-Targeted Drug Delivery Using Radiation Therapy.

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg phosphatidylethanolamine (PE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-disteroyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG-2000), and the mean size of the RTL was in the range of 114 to 133 nm, as measured by nanoparticle tracking analysis (NTA). The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three IV injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.

Physicochemical characteristics of pristine and functionalized graphene.

Graphene-based nanomaterials have received significant attention in the last decade due to their interesting properties. Its electrical and thermal conductivity and strength make graphene well suited for a variety of applications, particularly for use as a composite material in plastics. Furthermore, much work is taking place to utilize graphene as a biomaterial for uses such as drug delivery and tissue regeneration scaffolds. Owing to the rapid progress of graphene and its potential in many marketplaces, the potential toxicity of these materials has garnered attention. Graphene, while simple in its purest form, can have many different chemical and physical properties. In this paper, we describe our toxicity evaluation of pristine graphene and a functionalized graphene sample that has been oxidized for enhanced hydrophilicity, which was synthesized from the pristine sample. The samples were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, infrared spectroscopy, thermogravimetric analysis, zeta-potential, atomic force microscopy and electron microscopy. We discuss the disagreement between the size of imaged samples analyzed by atomic force microscopy and by transmission electron microscopy. Furthermore, the samples each exhibit quite different surface chemistry and structure, which directly affects their interaction with aqueous environments and is important to consider when evaluating the toxicity of materials both in vitro and in vivo. Copyright © 2017 John Wiley & Sons, Ltd.

Functionalized Nanocellulose Drives Neural Stem Cells toward Neuronal Differentiation.

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC-Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC-Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC-Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array.

Simultaneous Electrochemical Deposition of Cobalt Complex and Poly(pyrrole) Thin Films for Supercapacitor Electrodes.

Supercapacitors are beneficial as energy storage devices and can obtain high capacitance values greater than conventional capacitors and high power densities compared to batteries. However, in order to improve upon the overall cost, energy density, and charge-discharge rates, the electrode material of supercapacitors needs to be fine-tuned with an inexpensive, high conducting source. We prepared a Co(III) complex and polypyrrole (PPy) composite thin films (CoN4-PPy) that was electrochemically deposited on the surface of a glassy carbon working electrode. Cyclic voltammetry studies indicate the superior performance of CoN4-PPy in charge storage in acidic electrolyte compared to alkaline and organic solutions. The CoN4-PPy material generated the highest amount of specific capacitance (up to 721.9 F/g) followed by Co salt and PPy (Co-PPy) material and PPy alone. Cyclic performance studies showed the excellent electrochemical stability of the CoN4-PPy film in the acidic medium. Simply electrochemically depositing an inexpensive Co(III) complex with a high electrically conducting polymer of PPy delivered a superior electrode material for supercapacitor applications. Therefore, the results indicate that novel thin films derived from Co(III) metal complex and PPy can store a large amount of energy and maintain high stability over many cycles, revealing its excellent potential in supercapacitor devices.

Fabrication and characterization of hydroxypropyl guar-poly (vinyl alcohol)-nano hydroxyapatite composite hydrogels for bone tissue engineering.

Biocompatible bone implants composed of natural materials are highly desirable in orthopedic reconstruction procedures. In this study, novel and ecofriendly bionanocomposite hydrogels were synthesized using a blend of hydroxypropyl guar (HPG), poly vinyl alcohol (PVA), and nano-hydroxyapatite (n-HA) under freeze-thaw and mild reaction conditions. The hydrogel materials were characterized using various techniques. TGA studies indicate that both composites, HPG/PVA and HPG/PVA/n-HA, have higher thermal stability compared to HPG alone whereas HPG/PVA/n-HA shows higher stability compared to PVA alone. The HPG/PVA hydrogel shows porous morphology as revealed by the SEM, which is suitable for bone tissue regeneration. Additionally, the hydrogels were found to be transparent and flexible in nature. In vitro biomineralization study performed in simulated body fluid shows HPG/PVA/n-HA has an apatite like structure. The hydrogel materials were employed as extracellular matrices for biocompatibility studies. In vitro cell viability studies using mouse osteoblast MC3T3 cells were performed by MTT, Trypan blue exclusion, and ethidium bromide/acridine orange staining methods. The cell viability studies reveal that composite materials support cell growth and do not show any signs of cytotoxicity compared to pristine PVA. Osteoblastic activity was confirmed by an increased alkaline phosphatase enzyme activity in MC3T3 bone cells grown on composite hydrogel matrices.

Guar-Based Injectable Thermoresponsive Hydrogel as a Scaffold for Bone Cell Growth and Controlled Drug Delivery.

In this study, an injectable thermoresponsive hydroxypropyl guar-graft-poly(N-vinylcaprolactam) (HPG-g-PNVCL) copolymer was synthesized by graft polymerization. The reaction parameters such as temperature, time, monomer, and initiator concentrations were varied. In addition, the HPG-g-PNVCL copolymer was modified with nano-hydroxyapatite (n-HA) by in situ covalent cross-linking using divinyl sulfone (DVS) cross-linker to obtain HPG-g-PNVCL/n-HA/DVS composite material. Grafted copolymer and composite materials were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, proton nuclear magnetic resonance spectroscopy (1H NMR), and differential scanning calorimetry. The morphology of the grafted copolymer (HPG-g-PNVCL) and the composite (HPG-g-PNVCL/n-HA/DVS) was examined using scanning electron microscopy (SEM), which showed interconnected porous honeycomb-like structures. Using Ultraviolet-visible spectroscopy, low critical solution temperature for HPG-g-PNVCL was observed at 34 °C, which is close to the rheology gel point at 33.5 °C. The thermoreversibility of HPG-g-PNVCL was proved by rheological analysis. The HPG-g-PNVCL hydrogel was employed for slow release of the drug molecule. Ciprofloxacin, a commonly known antibiotic, was used for sustainable release from the HPG-g-PNVCL hydrogel as a function of time at 37 °C because of viscous nature and thermogelation of the copolymer. In vitro cytotoxicity study reveals that the HPG-g-PNVCL thermogelling polymer works as a biocompatible scaffold for osteoblastic cell growth. Additionally, in vitro biomineralization study of HPG-g-PNVCL/n-HA/DVS was conducted using a simulated body fluid, and apatite-like structure formation was observed by SEM.

Nanocrystalline Cellulose-Derived Doped Carbonaceous Material for Rapid Mineralization of Nitrophenols under Visible Light.

Nitrophenols (NPs) and related derivatives are industrially important chemicals, used notably to synthesize pharmaceuticals, insecticides, herbicides, and pesticides. However, NPs and their metabolites are highly toxic and mutagenic. They pose a serious threat to human health and ecosystem. Current work was undertaken to develop a suitable visible-light active catalyst for the sustainable and efficient mineralization of NPs in an aqueous environment. Nanocrystalline cellulose (NCs)-based nitrogen-doped titanium dioxide and carbonaceous material (N-TiO2/C) was synthesized by pyrolysis and sol-gel methods using NCs, polydopamine, and TiO2. The synthesized N-TiO2/C was characterized using different analytical techniques. Photocatalytic degradation of NPs under visible light indicated that acidic pH (3) was most suitable for the optimal degradation. 4-NP degradation followed both pseudo-first-order (R 2 = 0.9985) and Langmuir-Hinshelwood adsorption kinetic models (adsorption constant, K LH = 1.13 L mg-1). Gas chromatography-mass spectrometry and ion chromatography analysis confirmed the total mineralization of 4-NP into smaller molecular fragments such as acids, alcohols, and nitrates. The total organic carbon showed that 67% of total carbon present in 4-NP was mineralized into CO2 and CO. The catalyst was recycled for five consecutive cycles without losing its catalytic activities. The degradation mechanism of NPs with N-TiO2/C was also explored.