Uptake of surface-functionalized thermo-responsive polymeric nanocarriers in corticospinal tract motor neurons.

Nanocarrier drug delivery systems are attractive options for targeted delivery of survival- and regeneration-enhancing therapeutics to neurons damaged by degenerative or traumatic central nervous system (CNS) lesions. Functional groups on nanocarrier surfaces allow derivatization with molecules to target specific cells but may affect cellular interactions and nanocarrier uptake. We synthesized differently sized -COOH and -NH2 surface functionalized polymeric nanocarriers (SFNCs) by emulsion copolymerization and assessed uptake by different cell types in mixed cortical cultures. Following 60-min incubation with SFNCs, mean intensity measurements of fluorescently labeled SFNCs indicated that corticospinal tract motor neurons (CSMNs) took up more COOH- or NH2- functionalized SFNCs with similar sizes (150 nm), compared to glia. However, larger diameter (750 nm) SFNCs were taken up at higher concentrations compared to smaller COOH-derivatized SFNCs (150 nm). These data suggest that larger SFNCs may provide an advantage for enhanced uptake by targeted neurons.

Marriage of High-Throughput Gradient Surface Generation With Statistical Learning for the Rational Design of Functionalized Biomaterials.

Functional biomaterial is already an important aspect in modern therapeutics; yet, the design of novel multi-functional biomaterial is still a challenging task nowadays. When several biofunctional components are present, the complexity that arises from their combinations and interactions will lead to tedious trial-and-error screening. In this work, a novel strategy of biomaterial rational design through the marriage of gradient surface generation with statistical learning is presented. Not only can parameter combinations be screened in a high-throughput fashion, but also the optimal conditions beyond the experimentally tested range can be extrapolated from the models. The power of the strategy is demonstrated in rationally designing an unprecedented ternary functionalized surface for orthopedic implant, with optimal osteogenic, angiogenic, and neurogenic activities, and its optimality and the best osteointegration promotion are confirmed in vitro and in vivo, respectively. The presented strategy is expected to open up new possibilities in the rational design of biomaterials.

Polyethylene glycol and chitosan functionalized manganese oxide nanoparticles for antimicrobial and anticancer activities.

Biocompatible polymer-functionalized magnetic nanoparticles could offer promising applications in biomedical sciences. We fabricated polymer functionalized tri-manganese tetra oxide (Mn3O4) nanoparticles with the co-precipitation method and an octahedral crystal structure having a crystallite size of 10-17 nm was identified via XRD analyses. The SEM graph depicted the non-uniform and smooth surface of PEG-functionalized Mn3O4 NPs as compared to Mn3O4 and chitosan-coated Mn3O4 NPs. Elemental composition in the prepared sample was examined by EDX analysis. Various modes such as MnO, MnOH, OH, symmetric, and anti-symmetric of CH2 attached to the spectrum of Mn3O4 NPs were observed with FTIR analysis. The magnetization factor decreased and increase the coreacivity and retentivity of surface functionalized Mn3O4-NPs was calculated via VSM analysis. In-vitro bioassay, antibacterial activity was tested against Escherichiacoli, Bacillus cereus, and anti-fungal activities against two Fusarium strains indicated clear antimicrobial activities. The MTT assay to examine the anticancer activity against the MCF-7 cancer cell line was performed and the T1 MRI contrast agent demonstrated that PEG-coated Mn3O4 NPs exhibited anti-cancer activities. We propose that surface-functionalized magnetic NPs used for the treatment of cancer by using a remote controlled process of hyperthermia therapy.

Surface Design Options in Polymer- and Lipid-Based siRNA Nanoparticles Using Antibodies.

The mechanism of RNA interference (RNAi) could represent a breakthrough in the therapy of all diseases that arise from a gene defect or require the inhibition of a specific gene expression. In particular, small interfering RNA (siRNA) offers an attractive opportunity to achieve a new milestone in the therapy of human diseases. The limitations of siRNA, such as poor stability, inefficient cell uptake, and undesired immune activation, as well as the inability to specifically reach the target tissue in the body, can be overcome by further developments in the field of nanoparticulate drug delivery. Therefore, types of surface modified siRNA nanoparticles are presented and illustrate how a more efficient and safer distribution of siRNA at the target site is possible by modifying the surface properties of nanoparticles with antibodies. However, the development of such efficient and safe delivery strategies is currently still a major challenge. In consideration of that, this review article aims to demonstrate the function and targeted delivery of siRNA nanoparticles, focusing on the surface modification via antibodies, various lipid- and polymer-components, and the therapeutic effects of these delivery systems.

Development of bio-based material from the Moringa oleifera and its bio-coagulation kinetic modeling-A sustainable approach to treat the wastewater.

The development of bio-coagulants from Moringa oleifera seeds for sewage wastewater treatment has been investigated. The prepared bio-coagulant was treated with distilled water, HCl, NaOH, and NaCl to surface-functionalize the M. oleifera seed powder (MOSP). The bio-coagulant performance was investigated by monitoring the reduction of turbidity, EC, pH, TS, BOD, and COD from the wastewater. SEM, EDAX, and FTIR characterized the native and functionalized MOSP bio-coagulants. The HCl treated MOSP was found to be effective and have good coagulation activity (∼90%) compared to natural and other MOSPs. The turbidity removal by all the MOPS conformed to the WHO acceptable limit of finished water. Hence, maximum turbidity reduction was recorded in HCl > NaCl > NaOH > Natural (distilled water) treated MOSP. The pseudo-first and second-order kinetics rate also showed the effectiveness against turbidity reduction in municipal sewage water. Hence, the prepared MOSP bio-coagulants could be suitable for primary water treatments.

Design of a Sensitive Extracellular Vesicle Detection Method Utilizing a Surface-Functionalized Power-Free Microchip.

Extracellular vesicles (EVs), which are small membrane vesicles secreted from cells into bodily fluids, are promising candidates as biomarkers for various diseases. We propose a simple, highly sensitive method for detecting EVs using a microchip. The limit of detection (LOD) for EVs was improved 29-fold by changing the microchannel structure of the microchip and by optimizing the EV detection protocols. The height of the microchannel was changed from 25 to 8 µm only at the detection region, and the time for EV capture was extended from 5 to 10 min. The LOD was 6.3 × 1010 particles/mL, which is lower than the concentration of EVs in the blood. The detection time was 19 min, and the volume of EV solution used was 2.0 µL. These results indicate that an efficient supply of EVs to the detection region is effective in improving the sensitivity of EV detection. The proposed EV detection method is expected to contribute to the establishment of EV-based cancer point-of-care testing.

Fenton micro-reactor on a bubble: A novel microbubble-triggered simultaneous capture and catalytic oxidation strategy for recalcitrant organic pollutant removal.

A novel catalyst-functionalized microbubble system was developed to trigger both of the Fenton reaction and the flotation separation on the gas-liquid interface of bubbles for efficiently removing the recalcitrant organic pollutants from waters. The Fe(II)-functionalized colloidal microbubbles (FCMBs) were featured as large specific surface area, great bubble density and high ·OH activation capacity. Approximately 98.2% and 93.1% of the triphenylmethane and aromatic azo pollutants were removed within 0.5 min, respectively. Particularly, at the lowest Fe(II) dose of 0.2 mmol/L, the FCMB-triggered Fenton still achieved 7.4-20.6% higher removal than the traditional Fenton method at 0.5 min. In addition to the Fenton oxidative degradation mechanism, the FCMBs themselves were able to capture and remove 20.1-36.8% of pollutants from water. Thus, FCMBs served as micro-reactors in terms of: (i) the target molecules and intermediates were adhered and separated by FCMBs; and (ii) the FCMBs enhanced the mass transfer of catalyst and exposed sufficient active sites on the bubble surface for catalytic oxidation reaction. Compared with the traditional Fenton, the present method showed the robust tolerance of pH (4.0-9.5) and salinity (up to 40‰) at decreased Fe(II) doses, and the bio-toxicity of intermediates was obviously lower. The FCMB-triggered pollutant capture and catalytic oxidation technology exhibited a great potency in engineering implementation given the flexible bubble construction, the integration and simplification of treatment unit, as well as the decreased chemical doses.

Targeting foodborne pathogens via surface-functionalized nano-antimicrobials.

The incorporation of antibiotics and bioactive compounds into non-toxic nanoparticles has been popularly used to produce effective antimicrobial nanocarriers against foodborne pathogens. These systems can protect antimicrobials against harsh environments, control their release, and increase their antimicrobial activities; however, their functions can be decreased by some major barriers. Intracellular localization of bacteria protects them from the host immune system and antimicrobial agents. Also, bacteria can cause constant infection by nestling in professional phagocytic cells. In the last years, surface functionalization of nanocarriers by passive and active modification methods has been applied for their protection against clearance from the blood, increasing both circulation time and uptake by target cells. For achieving this objective, different functional agents such as specifically targeted peptides internalize ligands, saccharide ligands, or even therapeutic molecules (e.g., antibodies or enzymes) are used. In this review, techniques for functionalizing the surface of antimicrobial-loaded nanocarriers have been described. This article offers a comprehensive review of the potential of functional nanoparticles to increase the performance of antimicrobials against foodborne pathogens through targeting delivery.

Designing Better Cardiovascular Stent Materials - A Learning Curve.

Cardiovascular stents are life-saving devices and one of the top 10 medical breakthroughs of the 21st century. Decades of research and clinical trials have taught us about the effects of material (metal or polymer), design (geometry, strut thickness, and the number of connectors), and drug-elution on vasculature mechanics, hemocompatibility, biocompatibility, and patient health. Recently developed novel bioresorbable stents are intended to overcome common issues of chronic inflammation, in-stent restenosis, and stent thrombosis associated with permanent stents, but there is still much to learn. Increased knowledge and advanced methods in material processing have led to new stent formulations aimed at improving the performance of their predecessors but often comes with potential tradeoffs. This review aims to discuss the advantages and disadvantages of stent material interactions with the host within five areas of contrasting characteristics, such as 1) metal or polymer, 2) bioresorbable or permanent, 3) drug elution or no drug elution, 4) bare or surface-modified, and 5) self-expanding or balloon-expanding perspectives, as they relate to pre-clinical and clinical outcomes and concludes with directions for future studies.

Kinetic modelling of high turbid water flocculation using native and surface functionalized coagulants prepared from shed-leaves of Avicennia marina plants.

Coagulation performance of shed-leaves of Avicennia marina plants collected from Alang coastline, Gujarat (India) was scrutinized for the treatment of mud and starch water suspensions. For which, native, hydrochloric acid, sodium hydroxide and sodium chloride treated A. marina shed-leaves were processed with minimum environmental impact. Experiments were accomplished for the concentration of water suspensions (10-50 g/L) at the range of pH 7.0-8.0. The performances of these coagulants were assessed in terms of reduction in turbidity, pH, alkalinity, hardness, electrical conductivity and solids from water suspensions. The removal of bulk impurities was noted due to the floc formation of coagulant through hydrolysing salts, thus, resulted in the highest settlement at pH 7.82, 7.90 for mud and starch water, accordingly. Native and functionalized A. marina coagulants (AMCs) were characterized and interpreted using scanning electron microscopy, elemental analyses, energy dispersive and Fourier transform infrared spectroscopy. HCl treated AMC was relatively effective with good coagulation performance (96.76%), when compared with native and other treated AMCs. The turbidity removal by all AMCs obeyed with World Health Organization (WHO) acceptable limit of finished water, where HCl treated AMC clarified 15.15 and 16.36 NTU of mud and starch water suspensions to produce a clear water of 0.92 and 1.61 NTU, respectively. The proficiency of prepared AMCs were compared with other natural coagulants and surface functionalized (HCl > NaOH > NaCl) AMCs prepared in this study exerted better performance than the native AMC. The critical coagulation rate from the second-order kinetics were evaluated and the results were highly satisfying. Other physico-chemical parameters of water suspensions were evident for the adequate removal of impurities by non-toxic plant-based coagulants.

Multiplex MicroRNA Detection on a Surface-Functionalized Power-Free Microfluidic Chip.

Circulating microRNAs (miRNAs) have emerged as promising cancer biomarkers because their concentration profiles in body fluids are associated with the type and clinical stage of cancer. For multiplex miRNA detection, a novel surface-functionalized power-free microfluidic chip (SF-PF microchip) has been developed. The inner surface of the SF-PF microchip microchannels was functionalized via electron beam-induced graft polymerization and immobilization of capture probe DNAs. Simultaneous and specific duplex miRNA detection was achieved on the line-type SF-PF microchip with detection limits of 19.1 and 47.6 nmol L-1 for hsa-miR-16 and hsa-miR-500a-3p, respectively. Moreover, simultaneous and specific triplex miRNA detection was achieved on the stripe-type SF-PF microchip. The sample volume required for this microchip was 0.5 µL, and the time required for detection was 17 min. These results indicate that up to six types of miRNAs could be detected without compromising the advantages of the previous SF-PF microchips for cancer point-of-care testing.

Removal of micron-scale microplastic particles from different waters with efficient tool of surface-functionalized microbubbles.

Microplastic (MP) contamination in water has garnered significantly global concerns. The MP removal particularly challenges when the particle size decreases to several microns and other contaminants co-exist. This study used the coagulative colloidal gas aphrons (CCGAs) to simultaneously remove the micron-scale MP particles (~5 µm in diameter) and dissolved organic matter (DOM). Carboxyl-modified poly-(methyl methacrylate) (PMMA) and unsurface-coated polystyrene (PS) were chosen as target MPs. Over 94% of PS particles and almost 100% of color were simultaneously removed with lower CCGA consumption than the scenarios with either contaminant in water. The PMMA removal was not as high as the PS removal since the HA polyanions could compete with the negatively-charged PMMA for CCGAs. High salinity reduced the removal of HA by changing its interfacial behaviors without impacting the MP separation. In river water or influent of wastewater treatment plant, the MP particles were almost completely eliminated whereas the DOM (tyrosine-like or tryptophan-like) was partially removed. The fluorescence quenching titration revealed that CCGAs preferably captured the free DOM and the DOM-coated MP particles through complexation interaction. The study denoted that the CCGA system could be a robust tool for efficiently and synergistically removing micron-scale MPs and DOM from different water matrixes.

Lability-specific enrichment of typical engineered metal (oxide) nanoparticles by surface-functionalized microbubbles from waters.

Enrichment of metallic engineered nanoparticles (MENPs) from environmental waters is a prerequisite for their removal, reliable analyses, and environmental process interpretations. This work investigated the enrichment of typical MENPs with different degrees of lability using surface-functionalized microbbubles. During the process, the transformation/dissolution characteristics of MENPs were considered, and the impact of surfactant or coagulant dose, pH of MENP suspensions, and water matrix was systematically investigated. Results show that the colloidal gas aphrons (CGAs) were capable of enriching over 90.0% of ionic Ag(I) which ended up as AgBr and Ag2CO3 in floats when the pH of suspension was 6.0. The polyaluminum chloride-modified CGAs with positive surface charges were good at capturing the particulate ZnO-NPs (~84.8%) but failed to collect the ionic species. It should be noted that the total MENP enrichment efficiency closely related to the content proportions of different species. In the river water, both of the dissolved natural organic matter (fulvic acids) and the electrolytes might influence the enrichment process by affecting the species transformation of Ag-NPs and ZnO-NPs. For the stable TiO2-NPs, 97.1% of the nanoparticles were captured by CGAs. FAs apparently reinforced the enrichment performance since the molecules acted as bridge and facilitated the attachment between TiO2-NP and CGAs. This work contributes to establishing the robust microbubble-induced enrichment method considering the characteristics of MENP contaminants.

Surface-Functionalized Poly(Ether Sulfone) Composite Hollow Fiber Membranes with Improved Biocompatibility and Uremic Toxins Clearance for Bioartificial Kidney Application.

Bioartificial kidney (BAK) is attracting the focus of the research community. In this study, the efficacy of surface-functionalized poly(ether sulfone)-TPGS-graphene oxide composite hollow fiber membranes as a promising material for the single extracorporeal unit for BAK application was evaluated. The cytotoxicity was examined using human primary renal proximal tubular epithelial cells (hPTCs), and the removal of uremic toxins (urea, creatinine, phosphate, and lysozyme) from the toxin-spiked goat blood was measured. The surface-functionalized polymer composite membranes acted as a biocompatible material for attachment and proliferation of hPTCs, which was confirmed by microscopy studies, proliferation, and activity assays. The functional activity of these renal cells over this biocompatible membrane was also maintained. Remarkably, the functionalized composite membranes showed removal of urea (46.4 ± 3.5%), creatinine (52.2 ± 3.9%), phosphate (35.5 ± 2.7%), and lysozyme (11.2 ± 0.8%) from the toxin-spiked goat blood. Therefore, these obtained results showed that the surface-functionalized poly(ether sulfone)-TPGS-graphene oxide composite hollow fiber membranes are suitable for BAK application.

A Smart Nanotherapeutic Agent for in†vitro and in†vivo Reversal of Heavy-Metal-Induced Causality: Key Information from Optical Spectroscopy.

Human exposure to heavy metals can cause a variety of life-threatening disorders, affecting almost every organ of the body, including the nervous, circulatory, cardiac, excretory, and hepatic systems. The presence of heavy metal (cause) and induced oxidative stress (effect) are both responsible for the observed toxic effects. The conventional and effective way to combat heavy metal overload diseases is through use of metal chelators. However, they possess several side effects and most importantly they fail to manage the entire causality. In this study, we introduce citrate-functionalized Mn3 O4 nanoparticles (C-Mn3 O4 NPs) as an efficient chelating agent for treatment of heavy metal overload diseases. By means of UV/Vis absorbance and steady-state fluorescence spectroscopic techniques we investigated the efficacy of the NPs in chelation of a model heavy metal, lead (Pb). We also explored the retention of antioxidant properties of the Pb-chelated C-Mn3 O4 NPs using a UV/Vis-assisted DPPH assay. Through CD spectroscopic studies we established that the NPs can reverse the Pb-induced structural modifications of biological macromolecules. We also studied the in vivo efficacy of NPs in Pb-intoxicated C57BL/6j mice. The NPs were not only able to mobilize the Pb from various organs through chelation, but also saved the organs from oxidative damage. Thus, the C-Mn3 O4 NPs could be an effective nanotherapeutic agent for complete reversal of heavy-metal-induced toxicity through chelation of the heavy metal and healing of the associated oxidative stress.

Stable and sustainable photoanodes using zinc oxide and cobalt oxide chemically gradient nanostructures for water-splitting applications.

Amorphous cobalt oxide (CoO) encapsulated zinc oxide (ZnO) nanostructures were developed by adopting three low-temperature methods respectively atomic layer deposition, chemical bath deposition, and electrochemical deposition. The impact of CoO growth on the physical and chemical properties of ZnO nanostructures was investigated. Then, the ZnO/CoO core/shell nanostructures grown under optimized conditions were adopted for the fabrication of photoelectrochemical (PEC) water-splitting devices. The catalytic performance of ZnO nanostructures is substantially improved after their encapsulation with CoO layers. In addition, the chemical stability and durability of the structures are significantly enhanced. Under typical measurement conditions, these surface-modified ZnO nanostructures exhibited incident photon to charge carrier conversion efficiency (IPCE) higher than 16%, and a stable photocurrent density of 1.25 mA cm-2. Further, these ZnO/CoO nanostructured photoanodes showed a high illumination to dark current density ratio, ~2910.

AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts.

Cellular senescence may contribute to aging and age-related diseases and senolytic drugs that selectively kill senescent cells may delay aging and promote healthspan. More recently, several categories of senolytics have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors and natural compounds such as quercetin and fisetin. However, senolytic and senostatic potential of nanoparticles and surface-modified nanoparticles has never been addressed. In the present study, quercetin surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and their senolytic and senostatic activity was evaluated during oxidative stress-induced senescence in human fibroblasts in vitro. MNPQ promoted AMPK activity that was accompanied by non-apoptotic cell death and decreased number of stress-induced senescent cells (senolytic action) and the suppression of senescence-associated proinflammatory response (decreased levels of secreted IL-8 and IFN-ß, senostatic action). In summary, we have shown for the first time that MNPQ may be considered as promising candidates for senolytic- and senostatic-based anti-aging therapies.

Fenalan Yellow G adsorption using surface-functionalized green nanoceria: An insight into mechanism and statistical modelling.

In the present study, green nanoceria (gNC) was synthesized and surface-functionalized (sf-gNC) with amine moieties through chemical means and used as an adsorbent for the removal of Fenalan Yellow G (FYG) from the aqueous solution. Prior to the adsorption process, the optical, structural and textural characteristics of the nanomaterial ensured the presence of highly crystalline and monodisperse nanoceria with the functionalized amine group on their surfaces. The effects of the independent variables of the FYG removal process including initial solution pH, adsorbent dose, initial adsorbate concentration and time were examined for the percent removal. The maximum removal of 93.62% was observed at the pH of 2.0 with the adsorbent dose of 0.1 g for 10 mg/L of FYG dye concentration in 210 min. The equilibrium studies revealed that the maximum adsorption capacity was 25.58 mg/g by monolayer Langmuir model at 303 K and the chemical kinetics results followed pseudo-second-order and chemisorptive Elovich model. The magnitude of the energy variables from the thermodynamic analysis exposed the feasibility and spontaneity of endothermic adsorption. Furthermore, the interactive effects of the screened process variables investigated and optimized through response surface methodology (RSM). Besides, the FYG adsorption behavior was well predicted using artificial neural network (ANN) model with good accuracy (Mean Squared Error < 0.5; Coefficient of determination > 0.99) using 3 input layers, 3 hidden layers and 1 output layer. The study proposed the intrinsic mechanism of adsorbent-adsorbate interactions as either of electrostatic interaction or through surface complexation. Moreover, the prepared amine-modified nanoceria was found to have a minimum of 75% regenerative potential for five adsorption-desorption cycles.

Editorial of Special Issue "Surface-Functionalized Nanoparticles as Drug Carriers".

Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage forms. Over the decades, nanoparticles have been extensively used to increase bioavailability, improve solubility and stability, reduce toxicities, and facilitate the controlled release of therapeutics. Further, nanoparticles have often been surface-functionalized with a variety of ligands to enhance circulation half-life and increase target-specificity. Although nanotechnology has shown significant therapeutic benefits for multiple biomedical applications, limited nanoparticle-based formulations have progressed to clinical trials, and only a few have reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Surface-Functionalized Nanoparticles as Drug Carriers. We outline the scope of the special issue, summarize the results and conclusions of the nine articles published in this issue, and provide perspective on the application of surface-functionalized nanoparticles in the drug delivery field.

Surface-Functionalized Coating for Lithium-Rich Cathode Material To Achieve Ultra-High Rate and Excellent Cycle Performance.

Although the lithium-rich cathode material Li1.2Mn0.54Ni0.13Co0.13O2, as a promising cathode material, has a high specific capacity, it suffers from capacity decay and discharge voltage decay during cycling. In this work, the specific capacity and discharge voltage of Li1.2Mn0.54Ni0.13Co0.13O2 are stabilized by surface-functionalized LiCeO2 coating. We have conducted LiCeO2 coating via a mild synchronous lithium strategy to protect the electrode surface from electrolyte attack. This optimized LiCeO2 coating has high Li+ conductivity and abundant oxygen vacancies. The results demonstrate that 3% LiCeO2-coated Li1.2Mn0.54Ni0.13Co0.13O2 exhibits the highest capacity retention rate at 1, 2, and 5 C after 200 cycles, which were 84.3%, 85.4%, and 86.3%, respectively. The discharge specific capacity was almost 1.3, 1.4, and 1.4 times that of the pristine electrode. In addition, the 3% LiCeO2 electrode exhibited the least voltage decay of 0.409, 0.497, and 0.494 V at 1, 2, and 5 C, which was only about half of the pristine electrode. It should not be overlooked that the 3% LiCeO2 electrode still exhibits a high capacity at high current densities of 1250 mA g-1 (5 C) and 2500 mA g-1 (10 C), and its specific discharge capacities are 190.5 and 160.6 mAh g-1, respectively. These outstanding electrochemical properties benefit from surface-functionalized LiCeO2 coatings. To better understand the mechanism of oxygen loss of lithium-rich materials, we propose the lattice oxygen migration path of the LiCeO2-coated electrodes during the cycle. Our research provides a possible solution to the poor rate capability and cycle performance of cathode materials through surface-functionalized coatings.