Hybrid Carriers Research Articles

Tuning the surface charge and colloidal stability of hybrid gold-chitosan derivative nanoparticles for siRNA delivery

In recent years, the therapeutic potential of small interfering RNA (siRNA) has been confirmed by the emergence of commercially available siRNA-based drugs and by advances in the clinical trials phase. However, the many biological barriers faced by siRNA up to its delivery to the intended target make the advances in siRNA therapies highly dependent on the use of efficient gene vectors. In this study, the design of a new nanoparticle structured with a gold core and a diisopropylethylamine-chitosan shell was devised for application as a siRNA carrier. Thiol functionalized diisopropylethylamine-chitosan polymers were grafted onto gold nanoparticles (AuNPs) to obtain pH-responsive hybrid siRNA carriers (AuNP@polymers). The precise control of the diisopropylethylamine (DIPEA) graft and the tuning of the amount of polymer linked to the AuNPs enabled the assembly of hybrid carriers with good colloidal stability in physiological ionic strength (150 mmol L−1), sizes between 50 and 100 nm and positive zeta potentials (up to +17 mV), over a wide range of pH (5.5–7.4). The coated AuNPs were able to bind siRNA at N/P ratios in the range of 5–20, providing protection for the siRNA against RNAse degradation and making the hybrid vectors structurally and colloidally stable even in a protein-supplemented medium. The AuNP@polymers nanocarriers displayed non-cytotoxic effects in both 3T3/NIH fibroblast and HeLa-GFP cells up to an N/P ratio of 20 and the uptake of AuNP@polymers by RAW 264.7 macrophages was similar to Lipofectamine™ RNAiMAX. The zeta potential of the hybrid vectors was accurately adjusted by controlling the DIPEA graft and the pH of the formulation medium, which in turn drove the silencing efficiency of the siRNA nanocarrier as observed by the green fluorescent protein (GFP) knockdowns in HeLa cells. GFP knockdown levels close to that of Lipofectamine (up to 70 %) were achieved for the vectors formulated at pH 5.5. Overall, the results showed that the DIPEA-chitosan/AuNP association is a promising strategy to formulate hybrid nanocarriers for siRNA delivery with potential for in vivo studies.

Impact of species hybridization on the clinical management of schistosomiasis: A prospective study

BackgroundSpecies hybridization represents a real concern in terms of parasite transmission, epidemiology and morbidity of schistosomiasis. It is greatly important to better understand the impact of species hybridization for the clinical management. MethodsA prospective observational study was carried out in sub-Saharan migrants who were diagnosed with confirmed genitourinary schistosomiasis. A tailored protocol was applied, including Schistosoma serology, a specific urine LAMP tests for schistosomiasis and an ultrasound examination before treatment with praziquantel. A scheduled follow-up was performed at 3, 6 and 12 months to monitor treatment response, comparing patients carriers of Schistosoma hybrids with carriers of only genetically pure forms. ResultsA total of 31 male patients from West Africa were included in the study with a mean age of 26.5 years. Twelve (38.7 %) of the patients were carriers of Schistosoma hybrids. As compared with patients infected with S. haematobium alone, hybrid carriers had lower haemoglobin levels (13.8 g/dL [SD 1.8] vs 14.8 g/dL [SD 1.4], p = 0.04), a greater frequency of hematuria (100 % vs 52.6 %, p = 0.005), a higher ultrasound score (2.64, SD 2.20 vs 0.89, SD 0.99; p = 0.02). However, the presence of hybrids did not result in differences in clinical and analytical responses after treatment. ConclusionsThe presence of Schistosoma hybrids seems to cause increased morbidity in infected individuals. However, it does not appear to result in differences in diagnostic tests or in clinical and analytical responses after treatment.

Liposome-lentivirus for miRNA therapy with molecular mechanism study

BackgroundCancer stem cells (CSCs) play a vital role in the occurrence, maintenance, and recurrence of solid tumors. Although, miR-145-5p can inhibit CSCs survival, poor understanding of the underlying mechanisms hamperes further therapeutic optimization for patients. Lentivirus with remarkable transduction efficiency is the most commonly used RNA carrier in research, but has shown limited tumor-targeting capability.MethodsWe have applied liposome to decorate lentivirus surface thereby yielding liposome-lentivirus hybrid-based carriers, termed miR-145-5p-lentivirus nanoliposome (MRL145), and systematically analyzed their potential therapeutic effects on liver CSCs (LCSCs).ResultsMRL145 exhibited high delivery efficiency and potent anti-tumor efficacy under in vitro and in vivo. Mechanistically, the overexpressed miR-145-5p can significantly suppress the self-renewal, migration, and invasion abilities of LCSCs by targeting Collagen Type IV Alpha 3 Chain (COL4A3). Importantly, COL4A3 can promote phosphorylating GSK-3β at ser 9 (p-GSK-3β S9) to inactivate GSK3β, and facilitate translocation of β-catenin into the nucleus to activate the Wnt/β-catenin pathway, thereby promoting self-renewal, migration, and invasion of LCSCs. Interestingly, COL4A3 could attenuate the cellular autophagy through modulating GSK3β/Gli3/VMP1 axis to promote self-renewal, migration, and invasion of LCSCs.ConclusionsThese findings provide new insights in mode of action of miR-145-5p in LCSCs therapy and indicates that liposome-virus hybrid carriers hold great promise in miRNA delivery.Graphical abstract

TiO2-Mesoporous Ceria Carrier Modified with Sodium Benzoate: An Innovative Polyurethane Matrix for Enhanced Corrosion Protection of steel

An advanced corrosion protection system, distinguished by multilevel corrosion inhibition, was developed by integrating modified hybrid carriers strategically reinforced within a polyurethane (PU) matrix. For this purpose, mesoporous ceria (mCeO2) was synthesized via a hydrothermal hydrolysis process and incorporated with titanium butoxide to synthesize a hybrid core-shell titania mesoporous ceria (TiO2/mCeO2) carrier system. The TiO2/mCeO2 carrier system was modified with sodium benzoate (SB used as a corrosion inhibitor) to develop a modified TiO2/mCeO2-SB system. The synthesized modified particles were then reinforced into the polyurethane-based matrix to study the corrosion inhibition performance. Benefitting the corrosion-inhibiting properties of modified polyurethane-based coatings, the reinforcement of these modified TiO2/mCeO2 particles resulted in a notably improved anti-corrosion performance in the coating after immersion in 3.5 wt. % NaCl solution for four weeks, the impedance was estimated to be 96.65 GΩ.cm2, which is nearly four orders of magnitude than that of blank PU coatings. This is attributed to the synergistic anti-corrosion performance of TiO2 and SB. The protective layer formed due to the interaction of titania and hydroxyl ions resulted in the formation of Ti(OH)4 and SB absorbed on the steel surface, making iron unavailable for further electrochemical reaction. This work reports on the strategy to build a corrosion inhibition coating system, which introduces a new perspective for extending the lifespan of metals.

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles Per Se and Those Fused with Liposomes in Acidic Environment.

Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads. Despite their unique parameters, one of the major issues of virtually any nanoformulation is the ability to escape degradation in the compartment of endosomes and lysosomes which determines the overall efficiency of nanotherapeutics. In this study, we fabricated all major types of biological and hybrid NPs and studied their response to the acidic environment observed in the endolysosomal compartment. In this study, we show that EMNVs display increased protonation and swelling relative to EVs and NGs in an acidic environment. Furthermore, the hybrid NPs exhibit an even greater response compared to EMNVs. Short-term incubation of EMNVs in acidic pH corresponding to late endosomes and lysosomes again induces protonation and swelling, whereas hybrid NPs are ruptured, resulting in the decline in their quantities. Our findings demonstrate that in an acidic environment, there is enhanced rupture and release of vesicular cargo observed in hybrid EMNVs that are fused with liposomes compared to EMNVs alone. This was confirmed through PAGE electrophoresis analysis of mCherry protein loaded into nanoparticles. In vitro analysis of NPs colocalization with lysosomes in HepG2 cells demonstrated that EMNVs mostly avoid the endolysosomal compartment, whereas hybrid NPs escape it over time. To conclude, (1) hybrid biological NPs fused with liposomes appear more efficient in the endolysosomal escape via the mechanism of proton sponge-associated scavenging of protons by NPs, influx of counterions and water, and rupture of endo/lysosomes, but (2) EMNVs are much more efficient than hybrid NPs in actually avoiding the endolysosomal compartment in human cells. These results reveal biochemical differences across four major types of biological and hybrid NPs and indicate that EMNVs are more efficient in escaping or avoiding the endolysosomal compartment.

Исследование зависимости физико-химических свойств флуоресцентных гибридных полимерных носителей от условий гидротермального синтеза

Currently, the search for new types of carriers for low-molecular weight substances, as well as the development of optimal methods for the effective encapsulation of these substances are important tasks of modern chemistry and pharmacology. However, there are still limitations in this area, among which one of the most significant is the lack of the optimal carrier capable of stably retaining a low-molecular weight substance. The work presents hybrid polymer structures obtained by in situ hydrothermal synthesis as an effective candidate for these purposes. The fluorescent dye rhodamine B has been used as a model low-molecular weight substance for encapsulation into the structures. The resulting hybrid polymer structures demonstrated good stability when stored in an aqueous environment for 336 h with the release of the low-molecular weight dye rhodamine B no more than 2%. In addition, the influence of the conditions for obtaining hybrid carriers (including the composition of the carriers (thickness of the polymer shell and the presence of a calcium carbonate core) and synthesis temperature) on their physical-chemical characteristics has been studied. Thus, the optimal approach for obtaining fluorescent hybrid polymer carriers with a set of desired properties has been revealed. In particular, it has been shown that the optimal production conditions are hydrothermal synthesis temperature of 180 °C and the absence of CaCO 3 core inside the polyelectrolyte shell which allow us to obtain a stable hybrid polymer carrier with bright fluorescence. The results presented in this study can be used to create functional platforms and systems with tunable fluorescent properties and the ability to deliver low-molecular weight substances.

In situ-polymerized and nano-hybridized Ti3C2-MXene with PDA and Zn-MOF carrying phosphate/glutamate molecules; toward the development of pH-stimuli smart anti-corrosion coating

A smart anti-corrosion epoxy coating (EPC) was designed on the basis of polydopamine (PDA), and zeolitic imidazolate framework8 (ZIF8) tailored MXene (Ti3C2) sheets, which were loaded with two different corrosion inhibitors, namely phosphate and glutamate ions. The utilization of these inhibitor-loaded hybrid carriers in EPC yielded self-healing properties and prolonged resistance against corrosion. First, characterization tests including FT-IR, Raman, XRD, XPS, BET, TGA, SEM, and HRTEM were performed to confirm the synthesis of the constructed containers. Then, the inhibition efficiency and mechanism of the container were investigated via ICP and electrochemical (EIS and polarization) analyses. The synthesized PM-ZP and PM-ZG containers loaded with phosphate and glutamate inhibitors were proven to have a promising efficiency in reducing the corrosion of the metal, as the inhibition efficiency in the polarization test was demonstrated to be 42.17 and 60.31 %, respectively. The impedance values in the EIS test regarding solution media showed a considerable increment in PM-ZP (6511.3 Ω.cm2@3h) and PM-ZG (5438.3 Ω.cm2@5h) compared to the unprotected steel (2081.0 Ω.cm2@24 h). The self-healing potential of the nanocomposite containing PM-ZP and PM-ZG samples was manifested through the EIS test, FE-SEM as well as EDX maps of coatings with artificially produced scratches. The intact coatings’ long-term barrier characteristics were also investigated with an EIS test and impedance values > 40 Ω.cm2 and log|Z|10mHz > 10.5 justified the high performance of epoxy composites containing PM-ZP and PM-ZG synthesized carrier after 90 days of immersion in aggressive media. Pull-off, salt spray, and cathodic disbonding tests revealed that coatings containing PM-ZP and PM-ZG carriers outperformed epoxy coatings without corrosion inhibitors.

Synthesis and Utilisation of Hybrid Metal-Carbonic Anhydrase Enzyme Carrier System for Soil Biocementation

Biocementation is an emerging nature-inspired method of producing eco-friendly cement for soil stabilization. This paper used the bovine-derived carbonic anhydrase (CA) enzyme to catalyse the bioprecipitation of CaCO3 in a fine-grained soil and thus to biocement the soil. To increase the efficiency of the CA, an innovative copper–carbonic anhydrase (CA) hybrid was fabricated. This study is a proof-of-concept of the potential application of these enzyme carriers for soil biocementation. The hybrid carriers are aimed to enhance the stability, recovery and reusability of the enzyme used in the biocementation process. The results showed that the fabricated copper phosphate-based inorganic hybrid was stable throughout the duration of the tests (2 months) and under a wide range of pH and temperatures. Its enzymatic activity was enhanced compared to the free CA enzyme and it was proved suitable for soil biocementation. This was further confirmed by the SEM analysis. Additionally, the treated soil with the formulated hybrid carrier showed improved unconfined compressive strength, especially when the carriers were implemented into the soil by mixing. The material analysis by Raman spectroscopy confirmed calcium carbonate as the primary precipitate, consistent with soil biocementation. Overall, this innovative method of delivery of enzymes with enhanced stability and activity shows promise that, upon further development, it can be successfully used to increase the efficiency and sustainability of the biocementation process.

Self-aligned hybrid carrier-based PWM for modular multilevel converters

The self-aligned hybrid carrier-based pulse-width modulation (PWM) for modular multilevel converters (MMC) based on decentralized control is proposed in this paper. It is based on parallel cells in a submodule (SM) using self-aligned hybrid carrier-based PWM, which combines the concept of level-shifted carrier-based PWM (LSC-PWM) and phase-shifted carrier-based PWM (PSC-PWM) methods. By implementing a decentralized control system digitally, hybrid carriers align themselves. Each SM interacts with the other SMs and each parallel cell in an SM communicates with the other cells to generate hybrid carriers. The proposed control strategy makes advantage of the redundancy idea by adding or removing a cell in the case of cell malfunction and system reconfiguration. A current balancing method is incorporated into the decentralized control system to ensure current balance among parallel cells in an SM. The simulation results illustrate the effectiveness of the presented control method in piecewise linear electrical circuit simulation (PLECS) software.

Alginate-based ‘nano-micro’ hybrid matrices developed using ultrasonic atomization for Co-delivery of chemotherapeutic drugs against superficial tumors

Cancer has remained a life-threatening condition, with about 9.6 million deaths globally, despite the advancements and research in therapeutic approaches. Several chemotherapeutic agents are available which can reduce the size of tumors but have non-specific adverse effects on surrounding cells and the propensity to cause the formation of multi-drug resistant tumors. This report investigates a novel and facile method of ultrasonic atomization for the synthesis of Doxorubicin (Dox) loaded chitosan and Piperine (Pip) loaded Poly lactide-co-glycolide (PLGA) nanoparticles (Dox-Ch-NP, Pip-PLGA-NP). Further co-encapsulate these drug-loaded nanoparticles in hybrid alginate microspheres (HAM) using the same technique. The nanoparticles and microspheres were analyzed for size and morphology by DLS, SEM, TEM and CLSM. In vitro studies were performed to determine encapsulation efficiency, drug release and cell cytotoxicity. For the in-vivo evaluation of this co-delivery vehicle Swiss Albino Mice were used. The ultrasonic atomization process led to the development of Dox-Ch-NP (50–150 nm), Pip-PLGA-NP (50–200 nm) and HAM (5 μm). The encapsulation efficiency was 32% and 67% in the case of Dox-Ch-NP and Pip-PLGA-NP, respectively. Sustained in vitro release of both drugs was achieved for 15 days. MTT-based cell cytotoxicity assay shows 88% cell viability in HEK-293 and 51% in HeLa cells after 24Hrs of treatment with HAM. The in-vivo study suggested 93% of tumor reduction with Dox-Ch-NP treatment, 75% reduction with Pip-PLGA-NP treatment While 100% reduction in tumor volume after 15 days of treatment completion. The in-vivo study also showed higher and faster tumor volume reduction in co-delivered drugs via HAM than in single drug-loaded nanoparticles. The results indicate the successful formulation of multi-drug hybrid carriers which can aid in generating an efficient anti-tumor therapeutic regimen for localized tumors with reduced chances of occurrence of multi-drug resistant tumors.

PROMISING NANOBIOTECHNOLOGY FOR POULTRY FARMING BASED ON SILVER NANOPARTICLES EMBEDDED IN POLYMER-INORGANIC HYBRID CARRIERS

A promising composite material is proposed to reduce the endogenous and exogenous contamination of chicken eggs with pathogenic microflora during their formation and storage. It is based on hybrid biocompatible and biodegradable silica/polyacrylamide nanocarriers containing small silver nanoparticles (dav=2.4±1.0 nm) that are orally administered to laying hens with drinking water. The features of the formation of nanosilver in hybrid carriers by borohydride reduction of a silver salt at its various concentrations in an aqueous solution have been studied. An interesting effect of the sharp appearance of the second surface plasmon resonance band in the UV-Vis spectra of a silver salt/hybrid mixture at a high salt concentration was found. This was explained by sharp structural changes in the hybrid carriers caused by the simultaneous growth of many AgNPs in them. It was assumed that the intensive growth of many AgNPs in one hybrid particle was accompanied by detachment of the grafted PAAm chains from the SiO2 surface due to the breaking of hydrogen bonds. The change in the state of the composite material under the influence of the pH of the solution, the concentration of nanoparticles, the presence of NaCl (as in a “physiological solution”), and visible light was studied by UV-Vis spectroscopy, potentiometric titration, and TEM. Nanosilver in carriers showed high stability with respect to most of these factors. The influence of the composite material on the clinical state of laying hens and important parameters of their eggs and blood was studied when it was administered orally with drinking water three times every 10 days at doses of 0.2 and 0.4 mg per chicken per day. A striking effect of selective endogenous accumulation of silver in eggshells has been revealed. This confirmed the penetration of the nanosilver composite into the circulatory system of chickens by passing through the digestive tract, absorption through the intestinal epithelium and further transport into the tissues of the chickens, including the oviducts, where protein and eggshell are formed. Such penetration did not cause a toxic effect on the body of laying hens.

Lipid-Based Nanocarriers in the Treatment of Glioblastoma Multiforme (GBM): Challenges and Opportunities

Glioblastoma multiforme (also known as glioblastoma; GBM) is one of the most malignant types of brain tumors that occurs in the CNS. Treatment strategies for glioblastoma are majorly comprised of surgical resection, radiotherapy, and chemotherapy along with combination therapy. Treatment of GBM is itself a tedious task but the involved barriers in GBM are one of the main impediments to move one step closer to the treatment of GBM. Basically, two of the barriers are of utmost importance in this regard, namely blood brain barrier (BBB) and blood brain tumor barrier (BBTB). This review will address different challenges and barriers in the treatment of GBM along with their etiology. The role and recent progress of lipid-based nanocarriers like liposomes, solid lipid nanocarriers (SLNs), nanostructured lipid carriers (NLCs), lipoplexes, and lipid hybrid carriers in the effective management of GBM will be discussed in detail.

RETRACTED: Theoretical simulation and experimental design of selenium and gold incorporated polymer-based microcarriers for ROS-mediated combined photothermal therapy

Recently, multi-modal combined photothermal therapy (PTT) with the use of photo-active materials has attracted significant attention for cancer treatment. However, drug carriers enabling efficient heating at the tumor site are yet to be designed: this is a fundamental requirement for broad implementation of PTT in clinics. In this work, we design and develop hybrid carriers based on multilayer capsules integrated with selenium nanoparticles (Se NPs) and gold nanorods (Au NRs) to realize reactive oxygen species (ROS)-mediated combined PTT. We show theoretically and experimentally that cooperative interaction of Se NPs with Au NRs improves the heat release efficiency of the developed capsules. In addition, after uptake by tumor cells, intracellular ROS level amplified by Se NPs inhibits the tumor growth. As a consequence, the synergy between Se NPs and Au NRs exhibits the advantages of hybrid carriers such as (i) improved photothermal conversion efficiency and (ii) dual-therapeutic effect. The results of in vitro and in vivo experiments demonstrate that the combination of ROS-mediated therapy and PTT has a higher tumor inhibition efficiency compared to the single-agent treatment (using only Se-loaded or Au-loaded capsules). Furthermore, the developed hybrid carriers show negligible in vivo toxicity towards major organs such as the heart, lungs, liver, kidneys and spleen. This study not only provides a potential strategy for the design of multifunctional “all-in-one” carriers, but also contributes to the development of combined PTT in clinical practice.

Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy.

Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an in vitro fertilization (IVF) cycle remains only about 20%-30%, and 75% of these losses are due to implantation failure (the crucial rate-limiting step of gestation). Implantation failure and abnormal placenta formation are mainly caused by defective adhesion, invasion, and angiogenesis. Placental insufficiency endangers both the mother's and the fetus's health. Therefore, we suggested a novel treatment strategy to improve endometrial receptivity and implantation success rate. In this strategy, regulating mir-30d expression as an upstream transcriptomic modifier of the embryo implantation results in modified expression of the involved genes in embryonic adhesion, invasion, and angiogenesis and consequently impedes implantation failure. For this purpose, "scaffold/matrix attachment regions (S/MARs)" are employed as non-viral episomal vectors, transfecting into trophoblasts by exosome-liposome hybrid carriers. These vectors comprise CRISPR/dCas9 with a guide RNA to exclusively induce miR-30d gene expression in hypoxic stress conditions. In order to avoid concerns about the fetus's genetic manipulation, our vector would be transfected specifically into the trophoblast layer of the blastocyst via binding to trophoblast Erb-B4 receptors without entering the inner cell mass. Additionally, S/MAR episomal vectors do not integrate with the original cell DNA. As an on/off regulatory switch, a hypoxia-sensitive promoter (HRE) is localized upstream of dCas9. The miR-30d expression increases before and during the implantation and placental insufficiency conditions and is extinguished after hypoxia elimination. This hypothesis emphasizes that improving the adhesion, invasion, and angiogenesis in the uterine microenvironment during pregnancy will result in increased implantation success and reduced placental insufficiency, as a new insight in translational medicine.

Magnetic Porous Silica-lipid Bilayer Hybrid Carriers for Target Delivery of Curcumin

Mesoporous silica nanoparticles with embedded magnetic particles and sizes around 80 nm were prepared. Curcumin loading in mesoporous silica was realized by a post-synthesis impregnation procedure. The loaded particles were additionally modified by surface coating with a phospholipid bilayer of a thickness of around 5 nm changing the surface charge of the carrier from negative to positive, which enables the efficient attachment to cells, increasing the probability of cellular uptake. The non-loaded, curcumin loaded and their surface-coated counterparts were characterized by XRD, N2 physisorption, thermal analysis, TEM, and ATR-FTIR spectroscopy. Release experiments were performed and demonstrated that the phospholipid coating contributed greatly a sustained drug release to be achieved. A comparative study on the antiproliferative effect of curcumin loaded into the mesoporous carrier and lipid-coated vs. free drug was performed on a panel of three human cell lines. On the basis of the obtained results, it can be concluded that obtained hybrid magnetic silica-lipid particles are promising carriers of curcumin.

DNA-Liposome Hybrid Carriers for Triggered Cargo Release.

The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination with liposomes have great potential to render biocompatible hybrid carriers for triggered cargo release. We present an approach to form a DNA mesh on large unilamellar liposomes incorporating a stimuli-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence, a hairpin closes, and the DNA building block is allowed to self-contract. We demonstrate the actuation of this building block by single-molecule Förster resonance energy transfer (FRET), fluorescence recovery after photobleaching, and fluorescence quenching measurements. By triggering this process, we demonstrate the elevated release of the dye calcein from the DNA–liposome hybrid carriers. Interestingly, the incubation of the doxorubicin-laden active hybrid carrier with HEK293T cells suggests increased cytotoxicity relative to a control carrier without the triggered-release mechanism. In the future, the trigger could be provided by peritumoral nucleic acid sequences and lead to site-selective release of encapsulated chemotherapeutics.

Degradation of Hybrid Drug Delivery Carriers with a Mineral Core and a Protein-Tannin Shell under Proteolytic Hydrolases.

Hybrid carriers with the mineral CaCO3/Fe3O4 core and the protein–tannin shell are attractive for drug delivery applications due to reliable coupling of anticancer drugs with protein–tannin complex and the possibility of remote control over drug localization and delivery by the external magnetic field. This study aims to elucidate the mechanisms of drug release via enzymatic degradation of a protein–tannin carrier shell triggered by proteolytic hydrolases trypsin and pepsin under physiological conditions. To do this, the carriers were incubated with the enzyme solutions in special buffers to maintain the enzyme activity. The time-lapse spectrophotometric and electron microscopy measurements were carried out to evaluate the degradation of the carriers. It was established that the protein–tannin complex demonstrates the different degradation behavior depending on the enzyme type and buffer medium. The incubation in trypsin solution mostly resulted in the protein shell degradation. The incubation in pepsin solution did not affect the protein component; however, the citric buffer stimulates the degradation of the mineral core. The presented results allow for predicting the degradation pathways of the carriers including the release profile of the loaded cargo under physiological conditions. The viability of 4T1 breast cancer cells with mineral magnetic carriers with protein–tannin shells was investigated, and their movement in the fields of action of the permanent magnet was shown.

Hard, Soft, and Hard-and-Soft Drug Delivery Carriers Based on CaCO3 and Alginate Biomaterials: Synthesis, Properties, Pharmaceutical Applications.

Because free therapeutic drug molecules often have adverse effects on normal tissues, deliver scanty drug concentrations and exhibit a potentially low efficacy at pathological sites, various drug carriers have been developed for preclinical and clinical trials. Their physicochemical and toxicological properties are the subject of extensive research. Inorganic calcium carbonate particles are promising candidates as drug delivery carriers owning to their hardness, porous internal structure, high surface area, distinctive pH-sensitivity, low degradability, etc, while soft organic alginate hydrogels are also widely used because of their special advantages such as a high hydration, bio-adhesiveness, and non-antigenicity. Here, we review these two distinct substances as well as hybrid structures encompassing both types of carriers. Methods of their synthesis, fundamental properties and mechanisms of formation, and their respective applications are described. Furthermore, we summarize and compare similarities versus differences taking into account unique advantages and disadvantages of these drug delivery carriers. Moreover, rational combination of both carrier types due to their performance complementarity (yin-&yang properties: in general, yin is referred to for definiteness as hard, and yang is broadly taken as soft) is proposed to be used in the so-called hybrid carriers endowing them with even more advanced properties envisioned to be attractive for designing new drug delivery systems.

Вплив препарату наносрібла в носіях на основі полімер/неорганічних гібридів на мінеральний склад курячого посліду

Nanosilver preparation is synthesized in the carriers based on polymer/inorganic hybrids in aqueous dispersion form by in situ synthesis of silver nanoparticles in biocompatible and biodegradable polymer/inorganic hybrid based on silica sol and polyacrylamide. Hydrophilic polymer/inorganic hybrid used as a carrier for silver nanoparticles was synthesized by the developed method of directly grafting polyacrylamide "from" the unmodified surface of silica sol. The size of silver particles in the preparation was <10 nm. Studies have found that single, double and three-fold sprinkling of laying hens of nanosilver in polymer/inorganic hybrid carriers at concentrations of 1.0 and 2.0 mg/l (at doses of 0.2 and 0.4 mg per hen per day) did not affect the consumption of feed, water and egg productivity of poultry. The obtained nanosilver preparation is safe for laying hens and it does not cause disorders of clinical condition, diseases and poultry death during three-fold drinking with 10 days interval. After drinking the preparation of nanosilver to the laying hens at doses of 0.2 and 0.4 mg per head per day with an interval of 10 days, the dose-dependent amount of silver in the manure was increased only after a single drinking and after double and triple drinking, it did not affect the content of silver, copper, zinc, iron and lead. Single drinking of laying hens with a solution of silver nanoparticles in carriers based on polymer/hybrids at a concentration of 1.0 mg/l (0.2 mg per hen per day) increased the silver content in hen manure by 20% compared to the control group, and it did not affect the content of copper, zinc, iron and lead in manure. Nanosilver preparation at a concentration of 2.0 mg/l (0.4 mg per hen per day) increased the silver content by 44% in hen manure on the 10th day only after the first drinking of the preparation and it did not affect the content of copper, zinc, iron and lead compared to the control and with similar data of hens to which the same preparation was given at a concentration of 1.0 mg/l.

Real-Time Temperature Monitoring of Photoinduced Cargo Release inside Living Cells Using Hybrid Capsules Decorated with Gold Nanoparticles and Fluorescent Nanodiamonds.

Real-time temperature monitoring within biological objects is a key fundamental issue for understanding the heating process and performing remote-controlled release of bioactive compounds upon laser irradiation. The lack of accurate thermal control significantly limits the translation of optical laser techniques into nanomedicine. Here, we design and develop hybrid (complex) carriers based on multilayered capsules combined with nanodiamonds (NV centers) as nanothermometers and gold nanoparticles (Au NPs) as nanoheaters to estimate an effective laser-induced temperature rise required for capsule rupture and further release of cargo molecules outside and inside cancerous (B16-F10) cells. We integrate both elements (NV centers and Au NPs) in the capsule structure using two strategies: (i) loading inside the capsule's cavity (CORE) and incorporating them inside the capsule's wall (WALL). Theoretically and experimentally, we show the highest and lowest heat release from capsule samples (CORE or WALL) under laser irradiation depending on the Au NP arrangement within the capsule. Applying NV centers, we measure the local temperature of capsule rupture inside and outside the cells, which is determined to be 128 ± 1.12 °C. Finally, the developed hybrid containers can be used to perform the photoinduced release of cargo molecules with simultaneous real-time temperature monitoring inside the cells.