One-Pot Synthesis of Affordable Redox-Responsive Drug Delivery System Based on Trithiocyanuric Acid Nanoparticles.

Redox-responsive drug delivery systems present a promising avenue for drug delivery due to their ability to leverage the unique redox environment within tumor cells. In this work, we describe a facile and cost-effective one-pot synthesis method for a redox-responsive delivery system based on novel trithiocyanuric acid (TTCA) nanoparticles (NPs). We conduct a thorough investigation of the impact of various synthesis parameters on the morphology, stability, and loading capacity of these NPs. The great drug delivery potential of the system is further demonstrated in vitro and in vivo by using doxorubicin as a model drug. The developed TTCA-PEG NPs show great drug delivery efficiency with minimal toxicity on their own both in vivo and in vitro. The simplicity of this synthesis, along with the promising characteristics of TTCA-PEG NPs, paves the way for new opportunities in the further development of redox-responsive drug delivery systems based on TTCA.

A highly efficient and safe gene delivery platform based on polyelectrolyte core-shell nanoparticles for hard-to-transfect clinically relevant cell types.

While DNA and messenger RNA (mRNA) based therapies are currently changing the biomedical field, the delivery of genetic materials remains the key problem preventing the wide introduction of these methods into clinical practice. Therefore, the creation of new methods for intracellular gene delivery, particularly to hard-to-transfect, clinically relevant cell populations is a pressing issue. Here, we report on the design of a novel approach to format 50-150 nm calcium carbonate particles in the vaterite state and using them as a template for polymeric core-shell nanoparticles. We apply such core-shell nanoparticles as safe and efficient carriers for mRNA and pDNA. We prove that such nanocarriers are actively internalized by up to 99% of primary T-lymphocytes and exert minimal toxicity with the viability of >90%. We demonstrate that these nanocarriers mediate more efficient transfection compared with the standard electroporation method (90% vs. 51% for mRNA and 62% vs. 39% for plasmid DNA) in primary human T-lymphocytes as a model of the hard to transfect type that is widely used in gene and cell therapy approaches. Importantly, these polymeric nanocarriers can be used in serum containing basic culture medium without special conditions and equipment, thus having potential for being introduced in clinical development. As a result, we have provided proof-of-principle that our nanosized containers represent a promising universal non-viral platform for efficient and safe gene delivery.

Comprehensive Characterization of Titania Nanotubes Fabricated on Ti-Nb Alloys: Surface Topography, Structure, Physicomechanical Behavior, and a Cell Culture Assay.

In this study, hybrid composites based on ß-alloy Ti-xNb and oxide nanotubes (NTs) have been successfully prepared. NTs of different sizes were grown on Ti-Nb substrates with different Nb contents (5, 25, and 50 wt %) via electrochemical anodization at 30 and 60 V. Scanning electron microscopy imaging revealed that vertically aligned nanotubular structures form on the surface of Ti-Nb alloy substrates and influence Nb content in alloys based on NT length. X-ray diffraction analysis confirmed the formation of the anodized TiO2 layer and revealed several phases as the Nb content increased, starting with α' for low Nb content (5 wt %), the martensite α″ for intermediate Nb content (25 wt %), and the ß phase for the highest Nb content (50 wt %). Nanoindentation testing was used to evaluate the changes in mechanical properties of oxide NTs grown on Ti-Nb alloys with different compositions. NT arrays showed wide variations in Young's modulus and hardness depending upon the anodization voltage and the Nb content. The hardness and Young's modulus strongly correlated with NT morphology and structure. The highly dense morphology formed at a lower anodization voltage results in increased elastic modulus and hardness values compared with the surfaces prepared at higher anodization voltages. The nanostructurization of Ti-Nb surface substrates favored improved surface properties for the enhanced adhesion and proliferation of human mesenchymal stem cells (hMSCs). In vitro adhesion, spreading, and proliferation of hMSCs revealed the improved surface properties of the NTs prepared at an anodization voltage of 30 V compared with the NTs prepared at 60 V. Thus it can be concluded that NTs with diameters of ∼50 nm (at 30 V) are more favorable for cell adhesion and growth compared with NTs with diameters of 80 ± 20 nm (at 60 V). The surfaces of Ti-25Nb substrates anodized at 30 V promoted enhanced cell growth, as the further increase in Nb content in Ti-Nb substrate (Ti-50Nb) led to reduced cell proliferation. The application of NTs on Ti-Nb substrates leads to significant reductions in mechanical properties compared with those on the Ti-Nb alloy and improves cell adhesion and proliferation, which is vitally important for successful application in regenerative medicine.

Biological Kerker Effect Boosts Light Collection Efficiency in Plants.

Being the polymorphs of calcium carbonate (CaCO3), vaterite and calcite have attracted a great deal of attention as promising biomaterials for drug delivery and tissue engineering applications. Furthermore, they are important biogenic minerals, enabling living organisms to reach specific functions. In nature, vaterite and calcite monocrystals typically form self-assembled polycrystal micro- and nanoparticles, also referred to as spherulites. Here, we demonstrate that alpine plants belonging to the Saxifraga genus can tailor light scattering channels and utilize multipole interference effect to improve light collection efficiency via producing CaCO3 polycrystal nanoparticles on the margins of their leaves. To provide a clear physical background behind this concept, we study optical properties of artificially synthesized vaterite nanospherulites and reveal the phenomenon of directional light scattering. Dark-field spectroscopy measurements are supported by a comprehensive numerical analysis, accounting for the complex microstructure of particles. We demonstrate the appearance of generalized Kerker condition, where several higher order multipoles interfere constructively in the forward direction, governing the interaction phenomenon. As a result, highly directive forward light scattering from vaterite nanospherulites is observed in the entire visible range. Furthermore, ex vivo studies of microstructure and optical properties of leaves for the alpine plants Saxifraga "Southside Seedling" and Saxifraga Paniculata Ria are performed and underline the importance of the Kerker effect for these living organisms. Our results pave the way for a bioinspired strategy of efficient light collection by self-assembled polycrystal CaCO3 nanoparticles via tailoring light propagation directly to the photosynthetic tissue with minimal losses to undesired scattering channels.

Multifunctional Scaffolds with Improved Antimicrobial Properties and Osteogenicity Based on Piezoelectric Electrospun Fibers Decorated with Bioactive Composite Microcapsules.

The incorporation of bioactive compounds onto polymer fibrous scaffolds with further control of drug release kinetics is essential to improve the functionality of scaffolds for personalized drug therapy and regenerative medicine. In this study, polymer and hybrid microcapsules were prepared and used as drug carriers, which are further deposited onto polymer microfiber scaffolds [polycaprolactone (PCL), poly(3-hydroxybutyrate) (PHB), and PHB doping with the conductive polyaniline (PANi) of 2 wt % (PHB-PANi)]. The number of immobilized microcapsules decreased with increase in their ζ-potential due to electrostatic repulsion with the negatively charged fiber surface, depending on the polymer used for the scaffold's fabrication. Additionally, the immobilization of the capsules in dynamic mechanical conditions at a frequency of 10 Hz resulted in an increase in the number of the capsules on the fibers with increase in the scaffold piezoelectric response in the order PCL < PHB < PHB-PANi, depending on the chemical composition of the capsules. The immobilization of microcapsules loaded with different bioactive molecules onto the scaffold surface enabled multimodal triggering by physical (ultrasound, laser radiation) and biological (enzymatic treatment) stimuli, providing controllable release of the cargo from scaffolds. Importantly, the microcapsules immobilized onto the surface of the scaffolds did not influence the cell growth, viability, and cell proliferation on the scaffolds. Moreover, the attachment of human mesenchymal stem cells (hMSCs) on the scaffolds revealed that the PHB and PHB-PANi scaffolds promoted adhesion of hMSCs compared to that of the PCL scaffolds. Two bioactive compounds, antibiotic ceftriaxone sodium (CS) and osteogenic factor dexamethasone (DEXA), were chosen to load the microcapsules and demonstrate the antimicrobial properties and osteogenesis of the scaffolds. The modified scaffolds had prolonged release of CS or DEXA, which provided an improved antimicrobial effect, as well as enhanced osteogenic differentiation and mineralization of the scaffolds modified with capsules compared to that of individual scaffolds soaked in CS solution or incubated in an osteogenic medium. Thus, the immobilization of microcapsules provides a simple, convenient way to incorporate bioactive compounds onto polymer scaffolds, which makes these multimodal materials suitable for personalized drug therapy and bone tissue engineering.

Magnetic silica hybrids modified with guanidine containing co-polymers for drug delivery applications.

Guanidine containing co-polymers grafted onto silica nanoparticles to form core-shell structure were prepared by sol-gel method in the presence of γ-Fe2O3 nanoparticles. The morphological features for uncoated and coated silica particles have been characterized with scanning electron microscopy. The results show that the polymer coated silicas exhibit spherical morphology with rough polymeric surface covered by γ-Fe2O3 nanoparticles. The grafting amount of guanidine containing co-polymers evaluated by thermogravimetric analysis was in the range from 17 to 30%. Then, the drug loading properties and cumulative release of silica hybrids modified with guanidine containing co-polymers were evaluated using molsidomine as a model drug. It was shown that after polymer grafting the loading content of molsidomine could reach up to 3.42±0.21 and 2.34±0.14mg/g respectively. The maximum drug release of molsidomine is achieved at pH1.6 (approximately 71-75% release at 37°C), whereas at pH7.4 drug release is lower (50.4-59.6% release at 37°C). These results have an important implication that our magneto-controlled silica hybrids modified with guanidine containing co-polymers are promising as drug carriers with controlled behaviour under influence of magnetic field.