Polycaprolactone-based, porous CaCO3 and Ag nanoparticle modified scaffolds as a SERS platform with molecule-specific adsorption

Surface-enhanced Raman scattering (SERS) is a high-performance technique allowing detection of extremely low concentrations of analytes. For such applications, fibrous polymeric matrices decorated with plasmonic metal nanostructures can be used as flexible SERS substrates for analysis of analytes in many application. In this study, a three-dimensional SERS substrate consisting of a CaCO3-mineralized electrospun (ES) polycaprolactone (PCL) fibrous matrix decorated with silver (Ag) nanoparticles is developed. Such modification of the fibrous substrate allows achieving a significant increase of the SERS signal amplification. Functionalization of fibers by porous CaCO3 (vaterite) and Ag nanoparticles provides an effective approach of selective adsorption of biomolecules and their precise detection by SERS. This new SERS substrate represents a promising biosensor platform with selectivity to low and high molecular weight molecules

Polymeric and lipid membranes : from spheres to flat membranes and vice versa

Membranes are important components in a number of systems, where separation and control of the flow of molecules is desirable. Controllable membranes represent an even more coveted and desirable entity and their development is considered to be the next step of development. Typically, membranes are considered on flat surfaces, but spherical capsules possess a perfect infinite or fully suspended membranes. Similarities and transitions between spherical and flat membranes are discussed, while applications of membranes are also emphasized

Containers for drug delivery based on vaterite particles

Calcium carbonate is an important inorganic biomaterial thanks to its chemical stability, bioactivity, and biocompatibility. These properties have recently made it an interesting candidate for drug delivery systems. Calcium carbonate exists in three anhydrous polymorphic modifications: vaterite, aragonite, and calcite. Under normal conditions, vaterite is an unstable phase, while calcite and aragonite are stable. The transition between these phases can be exploited as a payload release mechanism. Vaterite polycrystalline particles have further favorable properties like high porosity, large surface area, and negative zeta potential. In our work we present a novel technique for the synthesis and characterization of CaCO3 containers. Porous polycrystalline particles were fabricated with controllable average sizes from 400 nm up to 10 microns. For demonstration a wide range of particles applications drug system as the enzyme alkaline phosphatase (ALP) and low molecular weight Fluorescent anticancer photosensitizer –“ sulfonated aluminum phthalocyanines” was encapsulated to study payload release dynamics. ALP is a popular model protein as it is easily detectable spectrophotometrically. Furthermore, it is responsible for mineralization of bone tissue in vivo. Hence, ALP-loaded vaterite could be applied for bone regeneration. In addition, ALP has been applied as an anti-inflammation drug to combat certain diseases. Several levels of control on these release dynamics could be identified: 1) The immersion medium: capsules immersed in water, showed a delayed burst release of the dye, coinciding with the crystal phase transition from vaterite to calcite. In ethanol this phase transition was inhibited, consequently only a slow desorption of the encapsulated dye was found. 2) Surface modification: Covering microcontainers with additional layers of biocompatible polyelectrolyte increases the payload release time. 3) pH value: A change of the pH from neutral to acid conditions will instead lead to a destruction of the vaterite matrix leading to an immediate release. Moreover, we report on studies of vaterite containers in cell culture assays, evaluating their cytotoxicity, their influence on cell viability, and the particles’ uptake efficiency. The prove of principle to use such particles with encapsulated photosensitizer for photodynamic therapy were demonstrated. These flexible control mechanisms and the perfect biocompatibility have proven the system’s potential for future pharmaceutical applications like drug delivery or bone reconstruction material. We would like to thank the Russian Federation (grant number 14.Z50.31.0004 to support scientific research projects implemented under the supervision of leading scientists at Russian institutions and Russian institutions of higher education), and RFBR research project №15-29-01172. BP acknowledges support of FWO (Fonds Wetenschappelijk Onderzoek

High-efficiency freezing-induced loading of inorganic nanoparticles and proteins into micron- and submicron-sized porous particles

We demonstrate a novel approach to the controlled loading of inorganic nanoparticles and proteins into submicron- and micron-sized porous particles. The approach is based on freezing/thawing cycles, which lead to high loading densities. The process was tested for the inclusion of Au, magnetite nanoparticles, and bovine serum albumin in biocompatible vaterite carriers of micron and submicron sizes. The amounts of loaded nanoparticles or substances were adjusted by the number of freezing/thawing cycles. Our method afforded at least a three times higher loading of magnetite nanoparticles and a four times higher loading of protein for micron vaterite particles, in comparison with conventional methods such as adsorption and coprecipitation. The capsules loaded with magnetite nanoparticles by the freezing-induced loading method moved faster in a magnetic field gradient than did the capsules loaded by adsorption or coprecipitation. Our approach allows the preparation of multicomponent nanocomposite materials with designed properties such as remote control (e.g. via the application of an electromagnetic or acoustic field) and cargo unloading. Such materials could be used as multimodal contrast agents, drug delivery systems, and sensors

In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers

We have developed a method for delivery of biocompatible CaCO3 microcontainers (4.0 ± 0.8 µm) containing Fe3O4 nanoparticles (14 ± 5 nm) into skin in vivo using fractional laser microablation (FLMA) provided by a pulsed Er:YAG laser system. Six laboratory rats have been used for the microcontainer delivery and weekly monitoring implemented using an optical coherence tomography and a standard histological analysis. The use of FLMA allowed for delivery of the microcontainers to the depth about 300 μm and creation of a depot in dermis. On the seventh day we have observed the dissolving of the microcontainers and the release of nanoparticles into dermis

Microstructured optical waveguide-based endoscopic probe coated with silica submicron particles

Microstructured optical waveguides (MOW) are of great interest for chemical and biological sensing. Due to the high overlap between a guiding light mode and an analyte filling of one or several fiber capillaries, such systems are able to provide strong sensitivity with respect to variations in the refractive index and the thickness of filling materials. Here, we introduce a novel type of functionalized MOWs whose capillaries are coated by a layer-by-layer (LBL) approach, enabling the alternate deposition of silica particles (SiO2) at different diameters—300 nm, 420 nm, and 900 nm—and layers of poly(diallyldimethylammonium chloride) (PDDA). We demonstrate up to three covering bilayers consisting of 300-nm silica particles. Modifications in the MOW transmission spectrum induced by coating are measured and analyzed. The proposed technique of MOW functionalization allows one to reach novel sensing capabilities, including an increase in the effective sensing area and the provision of a convenient scaffold for the attachment of long molecules such as protein

Biodegradable Nanocarriers Resembling Extracellular Vesicles Deliver Genetic Material with the Highest Efficiency to Various Cell Types

Efficient delivery of genetic material to primary cells remains challenging. Here, efficient transfer of genetic material is presented using synthetic biodegradable nanocarriers, resembling extracellular vesicles in their biomechanical properties. This is based on two main technological achievements: generation of soft biodegradable polyelectrolyte capsules in nanosize and efficient application of the nanocapsules for co‐transfer of different RNAs to tumor cell lines and primary cells, including hematopoietic progenitor cells and primary T cells. Near to 100% efficiency is reached using only 2.5 × 10−4 pmol of siRNA, and 1 × 10−3 nmol of mRNA per cell, which is several magnitude orders below the amounts reported for any of methods published so far. The data show that biodegradable nanocapsules represent a universal and highly efficient biomimetic platform for the transfer of genetic material with the utmost potential to revolutionize gene transfer technology in vitro and in vivo

The stress and vascular catastrophes in newborn rats: mechanisms preceding and accompanying the brain hemorrhages

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health