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

Gold nanoparticle coated silicon nitride chips for intracellular surface-enhanced Raman spectroscopy

Using surface-enhanced Raman spectroscopy on gold-nanoparticle-decorated silicon nitride chips, we monitor the release of dextran-rhodamin molecules from capsules inside living cells. This demonstrates the feasibility of using photonic chips for intracellular sensing at visible wavelengths

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

Progress in Isolation and Molecular Profiling of Small Extracellular Vesicles via Bead-Assisted Platforms

Tremendous interest in research of small extracellular vesicles (sEVs) is driven by the participation of vesicles in a number of biological processes in the human body. Being released by almost all cells of the body, sEVs present in complex bodily fluids form the so-called intercellular communication network. The isolation and profiling of individual fractions of sEVs secreted by pathological cells are significant in revealing their physiological functions and clinical importance. Traditional methods for isolation and purification of sEVs from bodily fluids are facing a number of challenges, such as low yield, presence of contaminants, long-term operation and high costs, which restrict their routine practical applications. Methods providing a high yield of sEVs with a low content of impurities are actively developing. Bead-assisted platforms are very effective for trapping sEVs with high recovery yield and sufficient purity for further molecular profiling. Here, we review recent advances in the enrichment of sEVs via bead-assisted platforms emphasizing the type of binding sEVs to the bead surface, sort of capture and target ligands and isolation performance. Further, we discuss integration-based technologies for the capture and detection of sEVs as well as future research directions in this field

Colloidal micro- and nano-particles as templates for polyelectrolyte multilayer capsules

Colloidal particles play an important role in various areas of material and pharmaceutical sciences, biotechnology, and biomedicine. In this overview we describe micro- and nano-particles used for the preparation of polyelectrolyte multilayer capsules and as drug delivery vehicles. An essential feature of polyelectrolyte multilayer capsule preparations is the ability to adsorb polymeric layers onto colloidal particles or templates followed by dissolution of these templates. The choice of the template is determined by various physico-chemical conditions: solvent needed for dissolution, porosity, aggregation tendency, as well as release of materials from capsules. Historically, the first templates were based on melamine formaldehyde, later evolving towards more elaborate materials such as silica and calcium carbonate. Their advantages and disadvantages are discussed here in comparison to non-particulate templates such as red blood cells. Further steps in this area include development of anisotropic particles, which themselves can serve as delivery carriers. We provide insights into application of particles as drug delivery carriers in comparison to microcapsules templated on them

Pharmacological aspects of release from microcapsules: from polymeric multilayers to lipid membranes

This review is devoted to pharmacological applications of principles of release from capsules to overcome the membrane barrier. Many of these principles were developed in the context of polymeric multilayer capsule membrane modulation, but they are also pertinent to liposomes, polymersomes, capsosomes, particles, emulsion-based carriers and other carriers. We look at these methods from the physical, chemical or biological driving mechanisms point of view. In addition to applicability for carriers in drug delivery, these release methods are significant for another area directly related to pharmacology modulation of the Permeability of the membranes and thus promoting the action of drugs. Emerging technologies, including ionic current monitoring through a lipid membrane on a nanopore, are also highlighted

Polyelectrolyte multilayer microcapsules templated on spherical, elliptical and square calcium carbonate particles

Recent studies have revealed that a variety of shaped particles can interact with cells in a different way. Elongated particles can be effectively and quickly internalized intercellularly compared with other configurations. Herein we present the potential of fabrication of anisotropic polyelectrolyte multilayer capsules formed by coating spherical, ellipsoid-like and square calcium carbonate (CaCO3) particles. By varying the intermixing speed, time, pH value and ratio of initial ingredients during precipitation such CaCO3 templates are produced. Particles loaded with FITC-dextran and coated with polyelectrolytes could maintain the templated shape after core removal. Quantitative data are derived from analysis of confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) measurements

Identification and Analysis of Exosomes by Surface-Enhanced Raman Spectroscopy

The concept of liquid biopsy has emerged as a novel approach for cancer screening, which is based on the analysis of circulating cancer biomarkers in body fluids. Among the various circulating cancer biomarkers, including Food and Drug Administration (FDA)-approved circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), exosomes have attracted tremendous attention due to their ability to diagnose cancer in its early stages with high efficiency. Recently, surface-enhanced Raman spectroscopy (SERS) has been applied for the detection of cancer exosomes due to its high sensitivity, specificity, and multiplexing capability. In this article, we review recent progress in the development of SERS-based technologies for in vitro identification of circulating cancer exosomes. The accent is made on the detection strategies and interpretation of the SERS data. The problems of detecting cancer-derived exosomes from patient samples and future perspectives of SERS-based diagnostics are also discussed.</jats:p