Polymer Capsules Research Articles

Long-term tracing of individual human neural cells using multiphoton microscopy and photoconvertible polymer capsules.

The study of human neural cells, their behaviour and migration are important areas of research in the biomedical field, particularly for potential therapeutic applications. The safety of using neural cells in therapy is still a concern due to a lack of information on long-term changes that may occur. While current methods of cell tracing explore gene manipulations, we elaborate approaches to cell marking with no genetic interference. In this study, we present a novel method for labelling and tracking neural cells using cell-impregnatable photoconvertible polyelectrolyte microcapsules. These capsules demonstrated low cytotoxicity with no effect on the differentiation ability of the neural cells, maintained a high level of fluorescent signal and ability for tracing individual neural cells for over 7 days. The capsules modified with rhodamine- and fluorescein-based dyes were demonstrated to undergo photoconversion by both one- and two-photon lasers while being internalized by neural cells. The finding gives the possibility to select individual capsules inside multicellular structures like spheroids and tissues and alternate their fluorescent appearance. Thus, we can track individual cell paths in complex systems. This new method offers a promising alternative for studying neural cells' long-term behaviour and migration in complex systems such as three-dimensional cellular populations.

Experimental and simulation-based engineering of calcium alginate self-healing asphalt capsules

An emerging technology to mitigate the cracking of asphalt pavements is the use of self-healing capsules embedded in asphalt mixtures. In this study, self-healing capsules were fabricated by encapsulating asphalt rejuvenators with calcium alginate shells. While past studies have used a “brute force” design process for such capsules, the design and formulation of these can be optimized through careful consideration of chemical interactions and crack healing mechanisms. In this study, experiments and molecular dynamics (MD) simulation were used to engineer capsule–rejuvenator formulations to mitigate premature failure of capsules and improve self-healing efficiency. To explore the thermodynamic process, the inter-diffusion coefficient and blending degree between materials in the capsule system were evaluated at different temperatures and capsule designs to determine the ratio of capsules which survive mixing and compaction through molecular scale studies. MD provided an understanding of healing behavior by simulating and quantifying the fracture–healing–fracture process of the binder–capsule system. The experiments verified the MD model by quantifying oil release percentage from micro-extraction and recovery and fine aggregate matrix (FAM) healing efficiency. The research revealed that the interaction between asphalt binder, rejuvenator, and capsules highly depended on their chemical compositions and that the dose of capsule content influences the penetration degree, and structural failure process. Polymeric capsules experienced significant premature failure and content release at high temperatures (160 °C) compared to intermediate temperatures (25 °C) due to enhanced thermal movement. To optimize capsule performance, rejuvenators C and E, which had higher viscosities, required 30%–40% calcium alginate, while rejuvenator A with lower viscosity needed 40%–60% calcium alginate. Rejuvenators with more asphaltenes were more sensitive to the capsule shell protection effect, and strengthened healing efficiency, while rejuvenators with more aromatics resulted in better wetting and diffusion processes during healing. The healing index, derived from FAM experimental healing test and validated by simulations, indicated that approximately 40% shell material effectively prevented capsule breakage and resulted in a 50% reduction in healing capacity. This research therefore established a framework for engineering a combination of capsules for use at pavement scale based on an understanding of chemical interactions, mechanical properties, and experimental verification.

Grapefruit‐Inspired Polymeric Capsule with Hierarchical Microstructure: Advanced Nanomaterial Carrier Platform for Energy Storage, Drug Delivery, Catalysis, and Environmental Applications (Small 30/2024)

Grapefruit‐Inspired Polymeric Capsule with Hierarchical Microstructure: Advanced Nanomaterial Carrier Platform for Energy Storage, Drug Delivery, Catalysis, and Environmental Applications (Small 30/2024)

Functionalized Calcium Carbonate-Based Microparticles as a Versatile Tool for Targeted Drug Delivery and Cancer Treatment.

Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness of silica-based carriers to spontaneous drug release. Calcium carbonate (CaCO3) is an emerging alternative, being an easily available, cost-effective, and biocompatible material with high porosity and surface reactivity, which makes it an attractive choice for targeted drug delivery. CaCO3 particles are used in this field in the form of either bare CaCO3 microbeads or core/shell microparticles representing polymer-coated CaCO3 cores. In addition, they serve as removable templates for obtaining hollow polymer microcapsules. Each of these types of particles has its specific advantages in terms of biomedical applications. CaCO3 microbeads are primarily used due to their capacity for carrying pharmaceutics, whereas core/shell systems ensure better protection of the drug-loaded core from the environment. Hollow polymer capsules are particularly attractive because they can encapsulate large amounts of pharmaceutical agents and can be so designed as to release their contents in the target site in response to specific stimuli. This review focuses first on the chemistry of the CaCO3 cores, core/shell microbeads, and polymer microcapsules. Then, systems using these structures for the delivery of therapeutic agents, including drugs, proteins, and DNA, are outlined. The results of the systematic analysis of available data are presented. They show that the encapsulation of various therapeutic agents in CaCO3-based microbeads or polymer microcapsules is a promising technique of drug delivery, especially in cancer therapy, enhancing drug bioavailability and specific targeting of cancer cells while reducing side effects. To date, research in CaCO3-based microparticles and polymer microcapsules assembled on CaCO3 templates has mainly dealt with their properties in vitro, whereas their in vivo behavior still remains poorly studied. However, the enormous potential of these highly biocompatible carriers for in vivo applications is undoubted. This last issue is addressed in depth in the Conclusions and Outlook sections of the review.

Grapefruit-Inspired Polymeric Capsule with Hierarchical Microstructure: Advanced Nanomaterial Carrier Platform for Energy Storage, Drug Delivery, Catalysis, and Environmental Applications.

Efficient support materials are crucial for maximizing the efficacy of nanomaterials in various applications such as energy storage, drug delivery, catalysis, and environmental remediation. However, traditional supports often hinder nanomaterial performance due to their high weight ratio and limited manageability, leading to issues like tube blocking and secondary pollution. To address this, a novel grapefruit-inspired polymeric capsule (GPC) as a promising carrier platform is introduced. The millimeter-scale GPC features a hydrophilic shell and an internal hierarchical microstructure with 80% void volume, providing ample space for encapsulating diverse nanomaterials including metals, polymers, metal-organic frameworks, and silica. Through liquid-phase bottom-up methods, it is successfully loaded Fe2O3, SiO2, polyacrylic acid, and Prussian blue nanomaterials onto the GPC, achieving high mass ratio (1776, 488, 898, and 634wt.%, respectively). The GPC shell prevents nanomaterial leakage and the influx of suspended solids, while its internal framework enhances structural stability and mass transfer rates. With long-term storage stability, high carrying capacity, and versatile applicability, the GPC significantly enhances the field applicability of nanomaterials.

Multiple dyes applications for fluorescent convertible polymer capsules as macrophages tracking labels

Tracing individual cell pathways among the whole population is crucial for understanding their behavior, cell communication, migration dynamics, and fate. Optical labeling is one approach for tracing individual cells, but it typically requires genetic modification to induce the generation of photoconvertible proteins. Nevertheless, this approach has limitations and is not applicable to certain cell types. For instance, genetic modification often leads to the death of macrophages. This study aims to develop an alternative method for labeling macrophages by utilizing photoconvertible micron-sized capsules capable of easy internalization and prolonged retention within cells. Thermal treatment in a polyvinyl alcohol gel medium is employed for the scalable synthesis of capsules with a wide range of fluorescent dyes, including rhodamine 6G, pyronin B, fluorescein, acridine yellow, acridine orange, thiazine red, and previously reported rhodamine B. The fluorescence brightness, photostability, and photoconversion ability of the capsules are evaluated using confocal laser scanning microscopy. Viability, uptake, mobility, and photoconversion studies are conducted on RAW 264.7 and bone marrow-derived macrophages, serving as model cell lines. The production yield of the capsules is increased due to the use of polyvinyl alcohol gel, eliminating the need for conventional filtration steps. Capsules entrapping rhodamine B and rhodamine 6G meet all requirements for intracellular use in individual cell tracking. Mass spectrometry analysis reveals a sequence of deethylation steps that result in blue shifts in the dye spectra upon irradiation. Cellular studies on macrophages demonstrate robust uptake of the capsules. The capsules exhibit minimal cytotoxicity and have a negligible impact on cell motility. The successful photoconversion of RhB-containing capsules within cells highlights their potential as alternatives to photoconvertible proteins for individual cell labeling, with promising applications in personalized medicine.

Seeded Growth of Plasmonic Nanostructures in Deformable Polymer Confinement.

Plasmonic nanostructures exhibit optical properties highly related to their morphologies, enabling diverse applications in various areas such as biosensing, bioimaging, chemical detection, cancer therapy, and solar energy conversion. The expansive uses of these nanostructures necessitate robust and versatile synthesis methods suitable for large-scale production. Here, we introduce our recent efforts in developing a new strategy for controlling the seeded growth of plasmonic metal nanostructures, employing deformable polymer capsules to regulate the growth kinetics and the resulting particle morphology. Employing sol-gel-derived resorcinol-formaldehyde (RF) resin as a typical capsule material, we highlight its advanced features, including mechanical deformability and molecular permeability, that can be manipulated by tuning the capsule thickness and cross-linking degree. These features enable highly controllable confined seeded growth of plasmonic nanostructures. We reveal the significant role of the Ostwald ripening process of the seeds and the capsule structures in determining the morphological evolution of the plasmonic nanostructures. Moreover, we highlight some distinctive plasmonic nanostructures resulting from this unique synthesis strategy and their intriguing functionalities in various potential applications. Our discussion concludes with potential research directions to advance the development of the deformable polymer-confined seeded growth strategy into a general and robust synthesis platform for creating cutting-edge functional plasmonic nanostructures.

3D printing of hybrid solid–liquid structures

Abstract3D printing is a versatile technology for creating objects with custom geometries and compositions and is increasingly employed for fabricating hybrid solid–liquid composites (SLCs). These composites, comprising solid matrices with integrated liquid components, showcase unique properties such as enhanced flexibility and improved thermal and electrical conductivities. This review focuses on methods to fabricate SLCs directly by different 3D printing techniques, e.g. without needing to backfill or impregnate a porous matrix. The techniques of extrusion, vat photopolymerization and material jetting combined with microfluidics, inkjet printing, vacuum filling and ultraviolet light curing to produce SLCs are emphasized. We also discuss the development of feedstocks, focusing on emulsions and polymer capsules as fillers, and analyze current literature to highlight their significance. The review culminates in a perspective on new directions, highlighting the potential of bicontinuous interfacially jammed emulsion gels (bijels) to facilitate the printing of continuous liquid pathways, alongside the importance of understanding ink formulation and stability. Concluding with future perspectives, we underline the transformative impact of 3D‐printed SLCs in diverse applications, signaling a significant advancement in the field. © 2024 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Visible Light Induced Interfacial Photo-Cross-Linking for Fabrication of Polymer Capsules Using Photoreactive Polymers with Substituted Cinnamates

Visible Light Induced Interfacial Photo-Cross-Linking for Fabrication of Polymer Capsules Using Photoreactive Polymers with Substituted Cinnamates

Shear strength recovery of sand with self-healing polymeric capsules

Self-healing approaches are increasingly being explored in various fields as a potential method to recover damaged material properties. By self-recovering without external intervention, self-healing techniques emerge as a potential solution to arrest or prevent the development of large strains problems in soils (e.g., landslides) and other ground effects that influence the serviceability of structures (e.g., differential settlement). In this study, a microcapsule-based self-healing sand was developed, and its performance during mixing and compaction, shearing, and recovery of shear strength was demonstrated. The cargo used for sand improvement, a hardening oil, tung oil, was encapsulated in calcium alginate capsules by the ionic gelation method. The surface properties, internal structure, thermal stability and molecular structure of the capsules were evaluated by advanced material characterization techniques. The survivability of capsules during mixing and compaction was assessed by measuring the content of tung oil released into the sand, while their influence on sand shear strength and its recovery was assessed with shear box tests. The results showed that the capsules could rupture due to movement of the sand particles, releasing the tung oil cargo, leading to its hardening and minimizing its strain-softening response and enhancing up to 76% of the sand shear strength (at a normal stress of 10 kPa and capsules content of 4%). This study demonstrates the potential of a capsules-based self-healing system to provide ‘smart’ autonomous soil strength recovery and thus with potential to actively control the large strain behavior of soils.

Photoinduced Toxicity Caused by Gold Nanozymes and Photodynamic Dye Encapsulated in Submicron Polymer Shell

AbstractThe development of nanozymes, artificial enzymes made from inorganic nanoparticles, is widely studied due to their affordability, durability, and strength. Gold nanoparticles (AuNPs) are employed to imitate peroxidase, glucose oxidase, lactate oxidase, superoxide dismutase, and catalase. The last one transforms intracellular hydrogen peroxide into molecular oxygen, whose deficiency is characteristic of the hypoxic tumor microenvironment. Thus, gold nanoparticles are thought to enhance the overall effectiveness of photodynamic therapy. However, the enzyme‐like activity of nanoparticles rapidly decreases in biological media, due to the aggregation and formation of the so‐called “protein corona”. In this study, polymeric submicrocapsules loaded with AuNPs and a photodynamic dye are fabricated via Layer‐by‐Layer (LbL) assembly. The enhancement of photodynamic treatment efficacy by in situ production of oxygen by the catalase‐like effect of AuNPs is investigated. Polymeric capsules are thoroughly characterized in terms of physicochemical and catalytic properties, and as a proof of concept, their therapeutic potential is evaluated in vitro. Furthermore, encapsulated AuNPs shows significantly lower aggregation both upon storage and during the reaction course. The results shows that the polymer capsules, containing AuNPs and photodynamic dye, show significantly higher light‐induced cytotoxicity in comparison to the individual photodynamic dye, suggesting a synergistic effect between the formation of molecular oxygen by catalase‐like gold nanozymes and photodynamic action.

Polymer‐based filaments with embedded magnetocaloric Ni‐Mn‐Ga Heusler alloy particles for additive manufacturing

AbstractOne important issue associated to magnetocaloric materials that hinders its technological application is the poor processability and structural integrity of those with the highest performance, usually intermetallics undergoing first‐order magnetic phase transitions. Additionally, the performance of these magnetocaloric materials highly depends on the structural stability of the magnetocaloric phase, which is, in many cases, very sensitive to temperature and mechanical processes. Additive manufacturing via the extrusion of polymer‐based composites is regarded as a promising way to overcome these issues. A recently presented manufacturing method of encapsulating functional fillers into polymer capsules has been used to produce a composite filament with a large load of magnetocaloric off‐stoichiometric Ni2MnGa Heusler alloy fillers with a uniform distribution throughout the polymer matrix as demonstrated by x‐ray tomography characterization. The incorporation of these metallic particles causes changes in the thermal behavior of the polymer as well as an increase in the flowability of the composite with respect to the polymer at the same temperature. The increased flowability of the composites found during manufacturing can be compensated by lowering the extrusion temperatures, making this technique even more convenient for preserving the filler properties, which is an important concern when additive manufacturing magnetocaloric materials. This is confirmed by the magnetic and magnetocaloric behavior of the composites, with responses proportional to the fraction of fillers.Highlights Ultrasonic‐atomization produces highly spherical Ni‐Mn‐Ga Heusler alloy particles. Ni‐Mn‐Ga filled polymer capsules allow a direct extrusion of composites for AM. X‐ray tomography shows uniform volumetric filler distribution within the filaments. Decreased viscosity of the matrix favors the lowering of the processing temperature. The low processing temperatures avoid altering the MCE of the alloy fillers.

Microfluidic Templating and Initiator‐Free Photocrosslinking of Protein‐Loaded PCL Microcapsules

AbstractPolymer network materials are interesting alternatives to thermoplastic polymers. Here, the preparation of polymer capsules is investigated, which are made from poly(ε‐caprolactone) (PCL) networks and are compartmentalized in a crosslinked PCL shell and a core that is suitable to enclose payloads of interest. Aided by microfluidic templating, PCL network capsules with a narrow size distribution (176 ± 5 µm) and thin shells (≈7.5 µm) are formed from 4‐arm star‐shaped 12 kDa PCL precursors by photoinitiator‐free UV light‐induced radical polymerization of methacrylate end‐groups. FITC‐BSA is encapsulated as a model protein. The physicochemical characterization of the capsules indicated a partial crosslinking of methacrylate endgroups into netpoints. Microscopy revealed a fraction of collapsed capsules that are discussed in the context of network stability and mechanical stress created at the capsule interfaces during solvent removal. The incubation of particles with human embryonic kidney (HEK) cells showed good cell compatibility, suggesting their potential use in biosciences and beyond.

Charged hollow microgel capsules.

Responsive hollow microgels are a fascinating class of soft model systems at the crossover between polymer capsules and microgels. The presence of the cavity makes them promising materials for encapsulation and controlled release applications but also confers them an additional softness that is reflected by their peculiar behaviour in bulk and at interfaces. Their responsivity to external stimuli, such as temperature, pH, and ionic strength, can be designed from their synthesis conditions and the choice of functional moieties. So far most studies have focused on "small" hollow microgels that were mostly studied with scattering or atomic force microscopy techniques. In our previous study, we have shown that large fluorescent hollow poly(N-isopropylacrylamide) (PNIPAM) microgels could be synthesized using micrometer-sized silica particles as sacrificial templates allowing their investigation in situ via confocal microscopy. In this work, we extend this approach to charged large hollow microgels based on poly(N-isopropylacrylamide-co-itaconic acid) (P(NIPAM-co-IA)). Hereby, we compare the structure and responsivity of "neutral" (PNIPAM) and "charged" (P(NIPAM-co-IA)) hollow microgel systems synthesized under similar conditions with the same sacrificial template using confocal and atomic force microscopy and light scattering techniques. In particular, we could demonstrate the extremely soft character of the swollen charged hollow microgels and their responsivity to pH, ionic strength, and temperature. To conclude this study, the buckling behavior of the different capsules was investigated illustrating the potential of such systems to change its conformation by varying the osmotic pressure and pH conditions.

Effect of photoconversion conditions on the spectral and cytotoxic properties of photoconvertible fluorescent polymer markers.

Fluorescence labeling of cells is a versatile tool used to study cell behavior, which is of significant importance in biomedical sciences. Fluorescent photoconvertible markers based on polymer microcapsules have been recently considered as efficient and perspective ones for long-term tracking of individual cells. However, the dependence of photoconversion conditions on the polymeric capsule structure is still not sufficiently clear. Here, we have studied the structural and spectral properties of fluorescent photoconvertible polymeric microcapsules doped with Rhodamine B and irradiated using a pulsed laser in various regimes, and shown the dependence between the photoconversion degree and laser irradiation intensity. The effect of microcapsule composition on the photoconversion process was studied by monitoring structural changes in the initial and photoconverted microcapsules using X-ray diffraction analysis with synchrotron radiation source, and Fourier transform infrared, Raman and fluorescence spectroscopy. We demonstrated good biocompatibility of free-administered initial and photoconverted microcapsules through long-term monitoring of the RAW 264.7 monocyte/macrophage cells with unchanged viability. These data open new perspectives for using the developed markers as safe and precise cell labels with switchable fluorescent properties.

Stimuli-Responsive CeO2 Removal Via Surface Redox Modulation during Shallow Trench Isolation (STI) Post-Chemical Mechanical Planarization (p-CMP)

As transistor miniaturization continues to extend Moore’s Law into the future of technology, the demand for high-efficiency device manufacturing processes has increased drastically in recent years. More specifically, a critical step in preparing integrated circuits (ICs) and logic devices is Chemical Mechanical Planarization (CMP), which relies on a delicate balance of chemical and mechanical parameters to achieve angstrom-level surface uniformity and ultimately allows for increased transistor packing density. A sub-area of CMP that has gained significant attention is Shallow Trench Isolation (STI), which involves the isolation of electrically active components by removing the bulk oxide (i.e., tetraethyl orthosilicate (TEOS)) overburden from the deposition process. During polishing, chemical slurries comprised of CeO2 nanoparticles, rate enhancers, selectivity and rheology modifiers, and pH adjusters are utilized to activate the oxide layer and consequently remove material. The STI removal mechanism, known as the chemical tooth model, involves the nucleophilic attack of CeO2 nanoparticles at surface defect states (i.e., oxygen vacancies (Ovacs)) and resultant dative Ce-O-Si bond formation, which makes the surface redox state of CeO2 (i.e., Ce3+/Ce4+) a key driver for oxide-nanoparticle interactions. It is well known that Ce3+ nanoparticles contain a higher concentration of Ovacs, which enhances the material removal rate (MRR). However, the hard adsorption properties of CeO2 have resulted in the demand for a more efficient post-CMP (p-CMP) cleaning process for TEOS that promotes increased CeO2 removal without inducing secondary defects (i.e., scratching, dishing, corrosion, etc.). Current industry-standard methods involve using a polyvinyl alcohol (PVA) brush to transport harsh chemistries to contaminated surfaces under high shear force (SF). Additionally, the use of megasonic energy is an emerging non-contact cleaning mode that relies on generating reactive oxygen species (ROS) (i.e., cavitations) to induce particle removal. Previous work has shown that supramolecular additives improve overall particle removal efficiency (PRE) when implemented in traditional PVA brush cleaning due to their ability to encapsulate and charge-flip CeO2 nanoparticles while reducing SF. As a result, this research investigates a combinatorial approach to PVA brush cleaning utilizing megasonic energy to release Fenton catalysts from polymer capsules, which aid in the production of ROS through H2O2 decomposition. Initial results have shown that, by increasing the concentration of ROS during cleaning, a Ce3+ à Ce4+ transition occurs on the surface of adsorbed CeO2, enhancing overall PRE.

Release of Redox Additives Via Megasonic Energy for High Selectivity/Low-Stress STI CMP

The advancements in a wide array of semiconductor manufacturing processing have been pivotal for the extension of Moore’s law the Chemical Mechanical Planarization (CMP) process has become an area of focus due to the stringent surface topography requirements. CMP utilizes complex slurry formulations containing abrasive nanoparticles and additives to reduce substrate defectivity and achieve angstrom-level uniformity. One area that has gained significant attention is Shallow Trench Isolation (STI), where the modulation and control of the surface oxidation state of the ceria, specifically the Ce3+ state, is critical to TEOS removal. In the Ce3+ state, defect states (i.e., oxygen vacancies (Ovacs)) on the surface are highly electron deficient (i.e., electrophilic) and allow the nucleophilic substrate to complex. By modulating the electrophilic properties of the particle, the kinetics of surface complexations required for effective TEOS removal can be controlled. This work focuses on developing stimuli-responsive capsules that can be added to STI slurry formulations to promote the controlled release of redox-active additives that can be used to drive the oxidation state of the CeO2 nanoparticle (Ce3+/Ce4+). By encapsulating the additive in a polymeric system, the reactive properties of the slurry are limited until the additive is released. In this work, megasonic action was employed to disrupt the capsules releasing the additives on demand to facilitate the modulation of the CeO2 surface redox states. Results have shown that the addition of a controlled-release capsule with an additive resulted in the increase of Ovacs at the CeO2 surface. This led to an increase from 1800 Å/min to 3450 Å/min using a constant 2.0 W/cm2 continuous flow megasonic flux. Furthermore, the overall defectivity decreased significantly with respect to both particle contamination and surface scratching. Lastly, the nature of the polymeric capsule has been shown to enhance selectivity between TEOS and silicon nitride and preliminarily appears to be megasonic flux dependent.

Surface morphology and oxidation evolution of glow discharge polymer capsules during tumble polishing

Glow discharge polymer (GDP) capsules are often used as the ablation layer in laser inertial confinement fusion (ICF) research, because of its excellent properties in low X-ray opacity, high tensile strength, and high thermal conductivity. The isolated surface defects and distribution of oxygen content on the surface of GDP capsules can lead to the increase of hydrodynamic instability and the decrease of compression efficiency. In this work, by using media spheres and silica nanoparticles, a tumble polishing device for GDP capsule polishing is built to improve the surface morphology. The effects of polishing parameters on the surface roughness and oxygen content of GDP were investigated. The test results show that tumble polishing can effectively remove convex defects, only 24 identified defects with a height below 231 nm were found after 144 h polishing, reduce the surface roughness (∼10 nm) and improve the surface quality of GDP capsules. Moreover, the oxygen content distribution on the surface of GDP is uniform after tumble polishing. And the depth analysis results show that the tumble polishing has no obvious effect on the change of oxygen content in GDP shell under the surface layer.

Multilayered Polymer Capsules for Targeted Delivery of Antitumor Compounds

Multilayered Polymer Capsules for Targeted Delivery of Antitumor Compounds

Polyelectrolyte Microcapsules as a Tool to Enhance Photosensitizing Effect of Chlorin E6

Introduction: Photodynamic therapy is a promising method of tumors treatment using photosensitizers and light of a certain wavelength. PS modification improves and enhances the phototoxic effect with decreased dark cytotoxicity. Materials and Methods: We compared the photosensitizing effect of polyelectrolyte microcapsules with chlorin E6 (ClE6) and free ClE6 at equivalent concentrations on murine fibroblast culture L929 using in vitro tests. Microcapsules were prepared layer by layer, sequentially depositing oppositely charged polyelectrolytes onto spherical CaCO3 particles. Cellular uptake of capsules was assessed using confocal microscopy. MTT test was used for a study of cell viability, and the relative amount of ROS was determined by the fluorescent method. Results: Microcapsules with ClE6 (in all tested concentrations) after exposure to red light (660 nm) reduced cell viability from 20% to 5%, while these capsules did not have dark cytotoxicity. Free ClE6 at the same concentrations as in the capsules after irradiation reduced viability from 65% to 35%. The level of ROS in the group of cells with capsules was 2 times higher compared to the group with CLE6. Discussion: The most probable mechanism of toxicity increase is creation of a higher ROS concentration and effect localization in the area of microcapsule interaction with the cell membrane. ROS production activation may stem from capsules providing a higher local PS concentration in the cell or nearby than the drug’s free form. Conclusion: The inclusion of chlorin E6 in polymer capsules reduced dark toxicity and increased the photosensitizing effect compared to the free form of ClE6.