Polyelectrolyte Capsules Research Articles

Fluorescent Convertible Capsule Coding Systems for Individual Cell Labeling and Tracking.

In modern biomedical science and developmental biology, there is significant interest in optical tagging to study individual cell behavior and migration in large cellular populations. However, there is currently no tagging system that can be used for labeling individual cells on demand in situ with subsequent discrimination in between and long-term tracking of individual cells. In this article, we demonstrate such a system based on photoconversion of the fluorescent dye rhodamine B co-confined with carbon nanodots in the volume of micron-sized polyelectrolyte capsules. We show that this new fluorescent convertible capsule coding system is robust and is actively uptaken by cell lines while demonstrating low toxicity. Using a variety of cellular lines, we demonstrate how this tagging system can be used for code-like marking and long-term tracking of multiple individual cells in large cellular populations.

Development of Multifunctional Coating of Textile Materials Using Silver Microencapsulated Compositions

The efficiency of the method for the synthesis of silver nanoparticles using a system containing oxalic dialdehyde as a reducing agent, and polyguanidine as a stabilizer is shown. An analysis of the data of photon correlation spectroscopy characterizing the sizes of the formed particles in the Ag-polyelectrolyte system is presented. It has been established that the synthesized silver nanoparticles have a stable biocidal effect. The system of biodegradable polyelectrolytes chitosan-xanthan gum for the synthesis of the capsule shell including silver nanoparticles is selected. This will allow the formation of stable polyelectrolyte capsule shells containing oyster mushroom mycelium extract. A protocol for the synthesis of microcapsules by the method of sequential adsorption of chitosan polyelectrolytes and xanthan gum on calcium carbonate templates was developed. Silver nanoparticles are included in the capsule shell, and a biologically active drug (oyster mushroom mycelium extract) is included in the core. The technological mode of complex capsules immobilization on a textile material by the layer-by-layer method is described. The immobilization of multilayer microcapsules on a fibrous substrate is provided by a system of polyelectrolytes: positively charged chitosan and negatively charged xanthan gum. The developed multifunctional coatings make it possible to impart multifunctional properties to textile materials: antibacterial, antimycotic, high hygroscopic properties.

Biodegradable polyelectrolyte/magnetite capsules for MR imaging and magnetic targeting of tumors.

Rationale: The tireless research for effective drug delivery approaches is prompted by poor target tissue penetration and limited selectivity against diseased cells. To overcome these issues, various nano- and micro-carriers have been developed so far, but some of them are characterized by slow degradation time, thus hampering repeated drug administrations. The aim of this study was to pursue a selective delivery of magnetic biodegradable polyelectrolyte capsules in a mouse breast cancer model, using an external magnetic field.Methods: Four different kinds of magnetic polyelectrolyte capsules were fabricated via layer-by-layer assembly of biodegradable polymers on calcium carbonate templates. Magnetite nanoparticles were embedded either into the capsules' shell (sample S) or both into the shell and the inner volume of the capsules (samples CnS, where n is the number of nanoparticle loading cycles). Samples were first characterized in terms of their relaxometric and photosedimentometric properties. In vitro magnetic resonance imaging (MRI) experiments, carried out on RAW 264.7 cells, allowed the selection of two lead samples that proceeded for the in vivo testing on a mouse breast cancer model. In the set of in vivo experiments, an external magnet was applied for 1 hour following the intravenous injection of the capsules to improve their delivery to tumor, and MRI scans were acquired at different time points post administration.Results: All samples were considered non-cytotoxic as they provided more than 76% viability of RAW 264.7 cells upon 2 h incubation. Sample S appeared to be the most efficient in terms of T2-MRI contrast, but the less sensitive to external magnet navigation, since no difference in MRI signal with and without the magnet was observed. On the other side, sample C6S was efficiently delivered to the tumor tissue, with a three-fold T2-MRI contrast enhancement upon the external magnet application. The effective magnetic targeting of C6S capsules was also confirmed by the reduction in T2-MRI contrast in spleen if compared with the untreated with magnet mice values, and the presence of dense and clustered iron aggregates in tumor histology sections even 48 h after the magnetic targeting.Conclusion: The highlighted strategy of magnetic biodegradable polyelectrolyte capsules' design allows for the development of an efficient drug delivery system, which through an MRI-guided externally controlled navigation may lead to a significant improvement of the anticancer chemotherapy performance.

A microwave-triggered opening of the multifunctional polyelectrolyte capsules with nanodiamonds in the shell composition

Microcapsules are ideal cargo platform for variety of applications such as drug delivery, sensing and imaging due to the combination of a simplicity fabrication and flexibility in the design. We developed remotely collapsing polymer capsules to response to external microwave treatment. The multilayer structure of the capsules was designed to create a polyfunctional system intercalating with nanodiamonds (NDs) and upconversion nanoparticles (UCNPs) into the polyelectrolyte shell. NDs empower local overheating to the microcapsules, while UCNPs provide opportunity to luminescent thermal sensing. UCNPs consist of inorganic crystalline host matrix - hexagonal β-phase NaYF4, doped with pairs of trivalent lanthanide ions, which play role of sensitizer (Yb3+) and activator (Er3+). The microwave triggering followed by the capsule heating results in the controlled destruction of the polyelectrolyte shell with subsequent cargo release. UCNPs luminescence was utilized to determine the local temperature of the capsule shell at nanoscale under GHz ultrasonic treatment. Our novel approach provides on demand microcapsule system destruction, which can be used in the development of nanotheranostic platform for the unification of diagnosis and treatment of various diseases.

Quantitative Assessment of Endosomal Escape of Various Endocytosed Polymer-Encapsulated Molecular Cargos upon Photothermal Heating.

Encapsulated molecular cargos are efficiently endocytosed by cells. For cytosolic delivery, understanding the dynamic process of cargos release from the carrier vehicles used for encapsulation and the lysosomes where the carrier vehicles are trapped (which in general is the bottleneck), followed by diffusion in the cytosol is important for improving drug/gene delivery strategies. A methodology is reported to image this process on a millisecond scale and to quantitatively analyze the data. Polyelectrolyte capsules with embedded gold nanostars to encapsulate 43 fluorescent molecular cargos with diverse properties, ranging from small fluorophores to fluorescently labeled proteins, siRNA, etc., are used. By short laser irradiation intracellular release of the molecular cargos from endocytosed capsules into the cytosol is triggered, and their intracellular spreading is imaged. Most of the released molecular cargos evenly distribute inside the entire cell, while others are enriched in certain cell compartments. The time the different molecular cargos take to distribute within cells, i.e., the spreading time, is used as a quantifier. Quantitative analysis reveals that intracellular spread cannot be described by free diffusion, but is determined by interaction of the molecular cargo with intracellular components.

The Influence of a Low-Frequency Magnetic Field on Polyelectrolyte Capsules with Magnetite Nanoparticles

The Influence of a Low-Frequency Magnetic Field on Polyelectrolyte Capsules with Magnetite Nanoparticles

Alginate microbeads with internal microvoids for the sustained release of drugs

The process of Ca2+ mediated gelation of alginate and the fabrication of nanoengineered polyelectrolyte capsules were combined for the preparation of alginate microbeads characterized by the presence of well-defined drug loaded microvoids in their volume.The obtained engineered alginate microbeads are described in terms of their morphology, loading efficiency and release characteristics. It was found that the generation of microvoids in the volume of alginate microbeads could be a promising approach for the creation of microstructured and biocompatible hydrogels, prospectively having highly tunable properties in terms of loading and releasing characteristics. In particular, it was found that the developed system was able to limit drug leakage during the gelation process and to control the initial burst release of small hydrophilic drug molecules, such as doxorubicin hydrochloride. Finally, the cytocompatibility of the developed microhydrogels was assessed on MCF-7 human breast cancer cells as well as their ability to sustain the release of the model drug during time.

The synthesis of CdSe quantum dots stabilized by polymers and polyelectrolyte capsules

The formation of nanocomposites based on quantum dots and polymers is a way of combining the benefits of quantum dots, such as their fundamental novelty and biomedical perspectives, with technological capabilities of polymers. The aim of this work was to synthesize cadmium selenide (CdSe) quantum dots in the presence of polymers (polyethyleneimine and chitosan) in an aqueous solution and embed cadmium selenide/polymer nanoparticles into polyelectrolyte capsules. To characterize the polymer-stabilized cadmium selenide quantum dots, the authors used fluorescence spectroscopy and dynamic and electrophoretic light scattering methods. The morphology of cadmium selenide/polymer nanoparticles characterized by the method of transmission electronic microscopy. The incorporation of quantum dots into a polymer matrix can significantly reduce their toxicity and prolong the duration of their fluorescence signals. Cadmium selenide nanoparticles stabilized by chitosan were used to synthesize five-layered polyelectrolyte capsules.

Polyelectrolyte hydrogel capsules as stabilizers for reconfigurable complex emulsions

Polyelectrolyte capsules stabilize biphasic oil droplets while preserving droplet reconfigurability in the presence of surfactants.

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.

Effect of Systemic Polyelectrolyte Microcapsule Administration on the Blood Flow Dynamics of Vital Organs.

Polyelectrolyte microcapsules and other targeted drug delivery systems could substantially reduce the side effects of drug and overall toxicity. At the same time, the cardiovascular system is a unique transport avenue that can deliver drug carriers to any tissue and organ. However, one of the most important potential problems of drug carrier systemic administration in clinical practice is that the carriers might cause circulatory disorders, the development of pulmonary embolism, ischemia, and tissue necrosis due to the blockage of small capillaries. Thus, the presented work aims to find out the processes occurring in the bloodstream after the systemic injection of polyelectrolyte capsules that are 5 μm in size. It was shown that 1 min after injection, the number of circulating capsules decreases several times, and after 15 min less than 1% of the injected dose is registered in the blood. By this time, most capsules accumulate in the lungs, liver, and kidneys. However, magnetic field action could slightly increase the accumulation of capsules in the region-of-interest. For the first time, we have investigated the real-time blood flow changes in vital organs in vivo after intravenous injection of microcapsules using a laser speckle contrast imaging system. We have demonstrated that the organism can adapt to the emergence of drug carriers in the blood and their accumulation in the vessels of vital organs. Additionally, we have evaluated the safety of the intravenous administration of various doses of microcapsules.

Salt-Triggered Release of Hydrophobic Agents from Polyelectrolyte Capsules Generated via One-Step Interfacial Multilevel and Multicomponent Assembly.

Controlled release of hydrophobic agents from salt-responsive capsules is hindered by the hydrophilic shell and interfacial tension between inner oil and surrounding water. Rupturing shells in salt solution is another effective way. However, the densely entangled polyelectrolytes (PEs) in shells determined that the rupture requires extremely high ion-strength. Herein, salt-responsive capsules with double-network shells including a continuous PE-nanocrystal network and interfacial ion pairs are proposed and revealed via a one-step interfacial multilevel and multicomponent assembly (IMMA) method. Rigid nanocrystals can weaken the entanglements of PE chains and reduce the critical salt-concentration. Interfacial ion pairs are responsible for maintaining the stability of the shells. Such double networks enable the disintegration of capsules in an applicable salt-concentration without damaging the stability of capsules. In addition, hydrophobic domains assemblied by surfactants and PE-nanocrystal network supply transport pathway for oil to across hydrophilic shells and subsequently produce inverse micelle to carry oil into water. The mechanism of formation and release of capsules is systematically investigated, which further demonstrates IMMA to be a typical method for creation of sophisticated structures in a brief way.

Controlling the Permeability of Polyelectrolyte Capsule Shells by Modifying Them with Haematin

The permeability of polyelectrolyte capsule shells is controlled by incorporating a natural hydrophobic pigment, haematin, into them via adsorption from an aqueous ammonia solution. The modification of capsules with the dye has been confirmed by the data of Raman light scattering and the measurements of the ζ potential. The capsules containing haematin in the shells have been characterized by spectrophotometry, atomic force microscopy, and scanning electron microscopy. Time variations in the surface charge, morphology, and thickness of the capsule shells have been discovered. Moreover, a decrease in the permeability of the modified capsule shells with respect to rhodamine 6G has been revealed. Polyelectrolyte capsules containing doxorubicin inside of them and haematin in their shells have been obtained. It has been shown that the drug is not spontaneously released into an aqueous medium over time.

Biodegradable Alginate Polyelectrolyte Capsules As Plausible Biocompatible Delivery Carriers.

Polyelectrolyte capsules made of different biodegradable and nonbiodegradable polymers can be designed as systems for effective encapsulation and delivery of compounds. The objective of this work was to synthesize biocompatible and biodegradable capsules (<1 μm) by the layer-by-layer (LbL) approach using alginate (ALGI) and poly-l-arginine (PARG) polyelectrolytes with a pH-sensitive outer layer of EUDRAGIT L 100 (EuL) polymer. Those capsules were loaded with curcumin as a model therapeutic drug, which possesses antioxidant, anti-inflammatory, and anticancer activity. Encapsulation of drugs inside capsules protects its therapeutic activity and increases its bioavailability. We report the capsule stability, loading efficiency, drug release, as well as capsule degradation studies as a function of pH. Furthermore, in vitro biocompatibility studies of capsules including cell viability and uptake studies were performed using HeLa cells. The here synthesized capsules exhibited good reproducibility, spherical shape, and high monodispersibility. The capsules showed good loading efficiency and drug release profile dependent upon pH environment. The in vitro studies indicate that the capsules exhibited acceptable biocompatibility and are highly internalized by cells. Our study thus suggests that alginate LbL capsules could be used as an efficient drug carrier with effective encapsulation and successful in vitro release of cargo in the cell.

Modification of the polyelectrolyte capsule shell by nanodiamonds for remote microwave opening

Nanodiamonds (ND) are one of the most attractive carbon materials for nanotechnology. The impregnation of NDs into the polymer capsule shell in the form of the single nanoparticles insures the control over the thermal conductivity of the capsule shell and increases their sensitivity to the external microwave irradiation. The polymer shell of the polyelectrolyte capsules was modified with NDs by electrostatic adsorption technique. The sensitivity of the capsules with embedded NDs to the external microwave irradiation was demonstrated by scanning electron microscopy leading to the shell rupture and release of the encapsulated agents.

The Effect of Focused Ultrasound on Magnetic Polyelectrolyte Capsules Loaded with Dye When Suspended in Tissue-Mimicking Gel.

Capsules containing a dye were prepared by the LbL method with iron oxide nanoparticles (50 nm) in different layers of the shell. The capsules were dispersed in a gel and subjected to focused ultrasonic irradiation at three different powers and exposure times. It was found that the inclusion of iron oxide magnetic nanoparticles in any of the polyelectrolyte shells (4, 6, 8 and 10) strengthened the capsules with respect to capsules without nanoparticles. Incorporation of nanoparticles in shell 8 provided the most resistance to fragmentation under focused ultrasonic irradiation. The relative degree of capsule stability is dependent on both the power of the ultrasound and the exposure time. The presence of iron oxide nanoparticles not only conferred more resistance to fragmentation but also provided a route to protein labelled dye release through sonoporation that was not present for capsules without nanoparticles.

Reusable Hollow Polymer Microreactors Incorporated with Anisotropic Nanoparticles for Catalysis Application.

We report a methodology to encapsulate gold nanorods (AuNRs) and gold bipyramids (AuBPs) into polyelectrolyte capsules for catalytic application. Microreactors (capsules with encapsulated NRs or BPs) were fabricated by sequential deposition of poly(allylamine hydrochloride) and dextran sulfate on modified sacrificial template, followed by core dissolution. AuNRs and AuBPs of size 25–30 nm were successfully encapsulated in the fabricated polyelectrolyte capsules and were stable and distributed uniformly in the interior. Fabricated microreactors were investigated as catalysts for the reduction of p-nitrophenol to p-aminophenol in the presence of sodium borohydride in aqueous phase. Reaction parameters such as order, conversion, and rate constants were estimated for microreactors and compared to free anisotropic nanoparticles in suspension. The reaction rate was higher for NRs in both free and capsule forms compared to BPs. Microreactors demonstrated excellent catalytic activity even after three times of use. Such capsules have high potential for use as microreactors in applications such as catalysis, drug delivery, imaging, and cancer chemo-photothermal therapy.

Encapsulation of Long Genomic DNA into a Confinement of a Polyelectrolyte Microcapsule: A Single-Molecule Insight.

Encapsulation of nucleic acids is an important technology in gene delivery, construction of “artificial cells”, genome protection, and other fields. However, although there have been a number of protocols reported for encapsulation of short or oligomeric DNAs, encapsulation of genome-sized DNA containing hundreds of kilobase pairs is challenging because the length of such DNA is much longer compared to the size of a typical microcapsule. Here, we report a protocol for encapsulation of a ca. 60 μm contour length DNA into several micrometer-sized polyelectrolyte capsules. The encapsulation was carried out by (1) compaction of T4 DNA with multivalent cations, (2) entrapment of DNA condensates into micrometer-sized CaCO3 beads, (3) assembly of polyelectrolyte multilayers on a bead surface, and (4) dissolution of beads resulting in DNA unfolding and release. Fluorescence microscopy was used to monitor the process of long DNA encapsulation at the level of single-DNA molecules. The differences between long and short DNA encapsulation processes and morphologies of products are discussed.

A Study of the Cytotoxic Effect of Microcapsules and Their Constituent Polymers on Macrophages and Tumor Cells.

We studied the effect of different concentrations of polyelectrolytes poly(allylamine hydrochloride) (PAH) and polystyrene sulfonate (PSS) as well as the effects of microcapsules coated with these polymers on survival of Ehrlich ascites carcinoma cells and mouse peritoneal macrophages and on ROS production by phagocytes. PAH reduced viability of Ehrlich ascites carcinoma in a concentration-dependent manner (LD50=12-15 μg/ml). This effect was presumably determined by its ability to bind phosphates, thereby depleting the culture medium. At the same time, PAH did not affect the viability of macrophages. PSS produced no cytotoxic effect on the examined cells. Polyelectrolyte capsules with the shell architectonics (PAH/PSS)3 and (PAH/PSS)3PAH in the examined concentration range had no effect on the viability of macrophages and tumor cells. PAH microcapsules with positively charged surface much more rapidly and more intensively activated macrophages. The chemiluminescence response directly depended on the amount of capsules in the solution.

Thermo-Induced Shrinking of “Dextran Sulfate/Polyarginine” Capsules with Magnetic Nanoparticles in the Shell

Polyelectrolyte capsules consisting of a combination of biodegradable polyelectrolytes, dextran sulfate/polyarginine, and magnetic nanoparticles have been prepared. The possibility of changing the sizes and morphology of the capsules by heating their aqueous suspension has been investigated. The efficiency of capsule shrinking doesn’t change when a layer of magnetic nanoparticles is introduced into the shell. The nanoparticles are uniformly distributed in the shell and do not aggregate during the process of its rearrangement under the influence of temperature.