Nanothermodynamics mediates drug delivery

© Springer International Publishing Switzerland 2015. The efficiency of penetration of nanodrugs through cell membranes imposes further complexity due to nanothermodynamic and entropic potentials at interfaces. Action of nanodrugs is effective after cell membrane penetration. Contrary to diffusion of water diluted common molecular drugs, nanosize imposes an increasing transport complexity at boundaries and interfaces (e.g., cell membrane). Indeed, tiny dimensional systems brought the concept of “nanothermodynamic potential,” which is proportional to the number of nanoentities in a macroscopic system, from either the presence of surface and edge effects at the boundaries of nanoentities or the restriction of the translational and rotational degrees of freedom of molecules within them. The core element of nanothermodynamic theory is based on the assumption that the contribution of a nanosize ensemble to the free energy of a macroscopic system has its origin at the excess interaction energy between the nanostructured entities. As the size of a system is increasing, the contribution of the nanothermodynamic potential to the free energy of the system becomes negligible. Furthermore, concentration gradients at boundaries, morphological distribution of nanoentities, and restriction of the translational motion from trapping sites are the source of strong entropic potentials at the interfaces. It is evident therefore that nanothermodynamic and entropic potentials either prevent or allow enhanced concentration very close to interfaces and thus strongly modulate nanoparticle penetration within the intracellular region. In this work, it is shown that nano-sized polynuclear iron (III)-hydroxide in sucrose nanoparticles have a nonuniform concentration around the cell membrane of macrophages in vivo, compared to uniform concentration at hydrophobic prototype surfaces. The difference is attributed to the presence of entropic and nanothermodynamic potentials at interfaces

Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis

© 2015, Spyropoulos-Antonakakis et al.; licensee Springer. Photodynamic therapy (PDT) involves the action of photons on photosensitive molecules, where atomic oxygen or OH− molecular species are locally released on pathogenic human cells, which are mainly carcinogenic, thus causing cell necrosis. The efficacy of PDT depends on the local nanothermodynamic conditions near the cell/nanodrug system that control both the level of intracellular translocation of nanoparticles in the pathogenic cell and their agglomeration on the cell membrane. Dendrimers are considered one of the most effective and promising drug carriers because of their relatively low toxicity and negligible activation of complementary reactions. Polyamidoamine (PAMAM) dendrite delivery of PDT agents has been investigated in the last few years for tumour selectivity, retention, pharmacokinetics and water solubility. Nevertheless, their use as drug carriers of photosensitizing molecules in PDT for cardiovascular disease, targeting the selective necrosis of macrophage cells responsible for atheromatous plaque growth, has never been investigated. Furthermore, the level of aggregation, translocation and nanodrug delivery efficacy of PAMAM dendrimers or PAMAM/zinc phthalocyanine (ZnPc) conjugates on human atheromatous tissue and endothelial cells is still unknown. In this work, the aggregation of PAMAM zero generation dendrimers (G0) acting as drug delivery carriers, as well as conjugated G0 PAMAM dendrimers with a ZnPc photosensitizer, to symptomatic and asymptomatic human carotid tissues was investigated by using atomic force microscopy (AFM). For the evaluation of the texture characteristics of the AFM images, statistical surface morphological and fractal analytical methodologies and Minkowski functionals were used. All statistical quantities showed that the deposition of nanodrug carriers on healthy tissue has an inverse impact when comparing to the deposition on atheromatous tissue with different aggregation features between G0 and G0/ZnPc nanoparticles and with considerably larger G0/ZnPc aggregations on the atheromatous plaque. The results highlight the importance of using PAMAM dendrimer carriers as a novel and promising PDT platform for atherosclerosis therapies

Fast Deoxynivalenol Determination in Cereals Using a White Light Reflectance Spectroscopy Immunosensor

Deoxynivalenol (DON) is a mycotoxin produced by certain Fusarium species and found in a high percentage of wheat and maize grains cultured worldwide. Although not so toxic as other mycotoxins, it exhibits both chronic and acute toxicity, and therefore methods for its fast and accurate on-site determination are highly desirable. In the current work, we employ an optical immunosensor based on White Light Reflectance Spectroscopy (WLRS) for the fast and sensitive immunochemical label-free determination of DON in wheat and maize samples. The assay is completed in 12 min and has a quantification limit of 2.5 ng/mL in buffer corresponding to 125 mu g/kg in whole grain which is lower than the maximum allowable concentrations set by the regulatory authorities for grains intended for human consumption. Several extraction protocols have been compared, and the highest recovery (>90%) was achieved employing distilled water. In addition, identical calibration curves were received in buffer and wheat/maize extraction matrix providing the ability to analyze the grain samples using calibrators in buffer. Recoveries of DON from spiked wheat and maize grain samples ranged from 92.0(+/- 4.0) to 105(+/- 4.0)%. The analytical performance of the WLRS immunosensor, combined with the short analysis time and instrument portability, supports its potential for on-site determinations

Selective immobilization of proteins guided by photo-patterned poly(vinyl alcohol) structures

AbstractThe development of “protein resistant” materials is challenging since protein hysisorption takes place on most surfaces due to van der Waals interactions, hydrogen bonding and entropy effects. In this work a new process for converting a surface resistant to protein adsorption is presented by using a photo-patternable poly(vinyl alcohol) (PVA) based film. This material minimizes effectively protein physisorption and it can be patterned through photolithography on top of any substrate. Herein the PVA-based film is patterned on top of a poly(styrene) (PS) film, in order to achieve selective protein patterning on the PS film and demonstrate the resistance of the PVA-based material to protein physisorption. The proposed methodology is expected to facilitate the fabrication of sensors and bioelectronic devices since it provides a patterning route with alignment capabilities for protein resistant-surfaces and it is based on an easy to implement process

Three-dimensional (3D) hierarchical oxygen plasma micro/nanostructured polymeric substrates for selective enrichment of cancer cells from mixtures with normal ones

The enrichment of cancer cell population when in mixtures with normal ones is of great importance for cancer diagnosis. In this work, poly(methyl methacrylate) films have been processed applying different oxygen plasma conditions to fabricate surfaces with structure height ranging from 22 to more than 2000 nm. The surfaces were then evaluated with respect to adhesion and proliferation of both normal and cancer human cells. In particular, normal skin and lung fibroblasts, and four different cancer cell lines, A431 (skin cancer), HT1080 (fibrosarcoma), A549 (lung cancer), and PC3 (prostate cancer), have been employed. It was found that adhesion and proliferation of cancer cells was favored when cultured onto the hierarchical micro/nanostructured surfaces as compared to untreated ones with the maximum values obtained for substrates treated at −100 V for 3 min. On the other hand, although the adhesion of normal fibroblasts was not influenced by the micro/nanostructured surfaces, their morphology and proliferation was significantly impaired, especially after 3-day culture on these surfaces. The reduced proliferation rate of adherent fibroblasts was linked to reduced focal points formation, as it was verified through vinculin staining, and not to apoptosis. The micro/nanostructured surfaces prepared with plasma treatment at −100 V for 3 min (hierarchical topography with mean height of ∼800 nm) were selected as substrates for normal and cancer cell co-culture experiments. It was found that 25–80 times enrichment of cancer over the normal cells was achieved on the nanostructured surfaces after 3-day culture, while it was 5–8 times lower on the untreated ones. It should be noticed that this is the first time such high enrichment ratios are achieved without implementing surfaces modified with binding molecules specific for cancer cells. Thus, the nanostructured surfaces hold a strong promise as culture substrates for separation and enrichment of cancer cells from mixtures with normal ones that should find application in cancer diagnostics. © 2019 Elsevier B.V

Bio-orthogonal fluorinated resist for biomolecules patterning applications

The patterning of organic materials on solid substrate surfaces has been demonstrated by several methods, such as photolithography, soft lithography, imprint lithography and ink-jet printing. Fluorinated polymers and solvents provide attractive material systems to develop new patterning approaches, as they are chemically orthogonal to non-fluorinated organic molecules, allowing their efficient incorporation in different devices and systems. Moreover, fluorinated polymers are soluble in hydrofluoroether solvents, benign to biomolecules, and can be properly engineered to enable efficient photolithographic patterning. In this work, we report the development of a new photolithographic process for patterning biomolecules on any kind of surfaces either by physical adsorption or covalent bonding. The photoresist is based on a fluorinated material and hydrofluoroether solvents that have minimum interactions with biomolecules and thus they can be characterized as orthogonal to the biomolecules (bio-orthogonal). In both cases, the creation of patterns with dimensions down to 2 μm was achieved. The implementation of the developed photolithographic procedure for the creation of a multi-protein microarray is demonstrated. © 2019 Elsevier B.V