Nano-sized Systems Research Articles

Fabrication of stable oleogel-in-water nanoemulsions with ethyl cellulose nanoparticles

Nanoemulsions (NEs) are liquid-based nanosized colloidal systems offering advantages (superior kinetic stability and rheology) compared to macro- and microemulsions. However, stabilization of these emulsions is difficult, since the small droplet sizes in NEs present large surface area-to-volume ratios. Thus, they need to be stabilized by superb emulsifiers to maintain stability. Herein, we report the construction of novel oleogel-in-water NEs with excellent stability against coalescence and phase separation. To do this, nanoparticles (NPs), based on ethylcellulose (EC), were first prepared, and then NEs were made using EC oleogel as the oil phase, ECNPs solution as the water phase, and tween-80 (TW80) as the surfactant. It was observed that NE stabilized by ECNPs, EC oleogel, and TW80 had a significantly lower particle size (201.86±1.57 nm), polydispersity index (0.13±0.06), with no phase separation over 30 days of storage as well as a higher zeta potential (-79.68±1.36 mV), and complex modulus (21441.80±418.21 kPa), as compared to the control NE (stabilized only by TW80). According to the findings, the developed NE has the potential for food and drug delivery applications.

Erythrocyte nano-ghosts with dual optical and magnetic resonance characteristics.

Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ) for nEGs fabricated using of BrCy112 is -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.

Preparation of nanoparticle and nanoemulsion formulations containing repaglinide and determination of pharmacokinetic parameters in rats

Repaglinide (RPG) belongs to the class of drugs known as meglitinides and is used for improving and maintaining glycemic control in the treatment of patients with Type 2 diabetes. RPG is a Class II drug (BCS) because of its high permeability and low water solubility. It also undergoes hepatic first-pass metabolism. The oral bioavailability of RPG is low (about 56 %) due to these drawbacks. Our aim in this study is to prepare two different nano-sized drug carrier systems containing RPG (nanoparticle: RPG-PLGA-Zein-NPs or nanoemulsion: RPG-NE) and to carry out a pharmacokinetic study for these formulations. We prepared NPs using PLGA and Zein. In addition, a single NE formulation was developed using Tween 80 and Pluronic F68 as surfactants and Labrasol as co-surfactant. The droplet size values of the blank-NE and RPG-NE formulations were found to be less than 120 nm. The mean particle sizes of blank-Zein-PLGA-NPs and RPG-Zein-PLGA-NPs were less than 260 nm. The Cmax and tmax values of RPG-Zein-PLGA-NPs and RPG-NE (523 ± 65 ng/mL and 770 ± 91 ng/mL; 1.41 ± 0.46 h and 1.61 ± 0.37 h, respectively) were meaningfully higher than those of free RPG (280 ± 33 ng/mL; 0.72 ± 0.28 h) (p < 0.05). The AUC0-∞ values calculated for RPG-Zein-PLGA-NPs and RPG-NE were approximately 4.04 and 5.05 times higher than that calculated for free RPG. These nanosized drug delivery systems were useful in increasing the oral bioavailability of RPG. Moreover, the NE formulation was more effective than the NP formulation in improving the oral bioavailability of RPG (p < 0.05).

Introducing Targeting Units or pH-Releasable Immunodrugs into Core-Clickable Nanogels

The development of nano-sized carrier systems plays a fundamental role in immunodrug delivery and the treatment of cancer. Especially functional materials, coupled with a stimuli-responsive drug release, control the selective delivery of small molecular drugs to the target site and avoid systemic side effects. Based on this, we introduce a DBCO core-functionalized nanogel platform for pH-reversible conjugation of highly potent TLR7/8-activating imidazoquinolines and the selective targeting of macrophage mannose receptor (MMR/ CD206) expressed by immunosuppressive macrophages. DBCO-PEG4-amine functionalized polymethacrylates are synthesized by controlled RAFT polymerization and self-assembled into precursor micelles in polar aprotic solvents. Corresponding nanogels are generated via reactive ester chemistry, while conjugated DBCO–units are incorporated into the core, still accessible for click reaction with azide-functionalized structures. Regarding the preparation of targeted nanogels, trimannose equipped with azide moieties can be conjugated to the DBCO nanogels, revealing the efficient targeting of macrophages’ mannose receptor in vitro. Moreover, the broad applicability of the DBCO nanogel is demonstrated by the synthesis of an azide–containing 2-propionic-3-methylmaleic anhydride-based linker sensitive for the pH–reversible conjugation of secondary amine-modified immune modulators, such as IMDQ-Me. Via bioorthogonal DBCO click reaction, the immune modulator can reversibly be conjugated, affording pH-responsive drug-loaded nanogels that conserve the desired immune stimulatory effect in vitro. Overall, these findings highlight the potential of core–functionalized DBCO nanogels, a promising carrier system for pH–sensitive conjugated immunodrugs as well as an attractive platform for controlled targeting of MMR. Altogether, the versatile application of core-functionalized DBCO nanogels may pave the way for enhancing bioorthogonal multifunctionality inside nanocarrier systems that assist in addressing multiple targets in cancer immunotherapy.

Fabrication of silver nanoparticles decorated on sodium alginate microbeads enriched with keratin and investigation of its catalytic and antioxidant activity

In this study, an environmentally friendly, effective, easily synthesizable and recoverable nano-sized catalyst system (Ag@NaAlg-keratin) was designed by decorating Ag nanoparticles on microbeads containing sodium alginate (NaAlg) and keratin obtained from goose feathers. The structure, morphology and crystallinity of the Ag@NaAlg-keratin nanocatalyst were evaluated by XRD, FT-IR, FE-SEM, EDS/EDS mapping and TEM analyses. Catalytic ability of designed Ag@NaAlg-keratin nanocatalyst was then investigated against 4-nitrophenol (4-NP) and methyl orange (MO) reductions. Ag@NaAlg-keratin nanocatalyst effectively reduced 4-NP in 6 min and MO in 5 min, with rate constants of 0.17 min−1 and 0.16 min−1, respectively. Additionally, activation energies (Ea) were found as 39.8 kJ/mol for 4-NP and 37.9 kJ/mol for MO. Performed recyclability tests showed that the Ag@NaAlg-keratin nanocatalyst was easily recovered due to its microbead form and successfully reused five times, maintaining both its activity and structure. Furthermore, antioxidant activity of Ag@NaAlg-keratin nanocatalyst was the highest (73.16 %).

Poly(amino acid)-based drug delivery nanoparticles eliminate Methicillin resistant Staphylococcus aureus via tunable release of antibiotic

Bacterial infections threaten public health, and novel therapeutic strategies critically demand to be explored. Herein, poly(amino acid) (PAA)-based drug delivery nanoparticles (NPs) were designed for eliminating Methicillin resistant Staphylococcus aureus (MRSA) via tunable release of antibiotic. Using N-acryloyl amino acids (valine, valine methyl ester, aspartic acid, serine) as monomers, four kinds of amphiphilic PAAs were synthesized via photoinduced electron/energy transfer–reversible addition fragmentation chain-transfer (PET-RAFT) polymerization and were further assembled into nano-sized delivery systems. Their assemble behavior was drove mainly by hydrophobic/hydrophilic interaction, which determined the particle size, efficacy of drug loading and release; but numerous hydrogen bonding (HB) interaction also played an important role in regulating morphologies of the NPs and enriching drug-binding capacity. By changing the HB- and hydrophobic-interaction of the PAAs, the particle sizes (240.7 nm-302.7 nm), the drug loading efficiency (9.57%-19.76%), and the Rifampicin (Rif) release rate (49.6%-69.7%) of the PAA-based NPs could be tunable. Specially, the antimicrobial properties of the Rif-loaded NPs are found to be related to the release of Rif, which was determined by its hydrophobic interaction with hydrophobic blocks and HB interaction with hydrophilic blocks. These studies provide a new outlook for the design of delivery systems for the therapy of bacterial infection.

Impact of conjugation to different lipids on the lymphatic uptake and biodistribution of brush PEG polymers

Delivery to peripheral lymphatics can be achieved following interstitial administration of nano-sized delivery systems (nanoparticles, liposomes, dendrimers etc) or molecules that hitchhike on endogenous nano-sized carriers (such as albumin). The published work concerning the hitchhiking approach has mostly focussed on the lymphatic uptake of vaccines conjugated directly to albumin binding moieties (ABMs such as lipids, Evans blue dye derivatives or peptides) and their subsequent trafficking into draining lymph nodes. The mechanisms underpinning access and transport of these constructs into lymph fluid, including potential interaction with other endogenous nanocarriers such as lipoproteins, have largely been ignored. Recently, we described a series of brush polyethylene glycol (PEG) polymers containing end terminal short-chain or medium-chain hydrocarbon tails (1C2 or 1C12, respectively), cholesterol moiety (Cho), or medium-chain or long-chain diacylglycerols (2C12 or 2C18, respectively). We evaluated the association of these materials with albumin and lipoprotein in rat plasma, and their intravenous (IV) and subcutaneous (SC) pharmacokinetic profiles. Here we fully detail the association of this suite of polymers with albumin and lipoproteins in rat lymph, which is expected to facilitate lymph transport of the materials from the SC injection site. Additionally, we characterise the thoracic lymph uptake, tissue and lymph node biodistribution of the lipidated brush PEG polymers following SC administration to thoracic lymph cannulated rats. All polymers had moderate lymphatic uptake in rats following SC dosing with the lymph uptake higher for 1C2-PEG, 2C12-PEG and 2C18-PEG (5.8%, 5.9% and 6.7% dose in lymph, respectively) compared with 1C12-PEG and Cho-PEG (both 1.5% dose in lymph). The enhanced lymph uptake of 1C2-PEG, 2C12-PEG and 2C18-PEG appeared related to their association profile with different lipoproteins. The five polymers displayed different biodistribution patterns in major organs and tissues in mice. All polymers reached immune cells deep within the inguinal lymph nodes of mice following SC dosing. The ability to access these immune cells suggests the potential of the polymers as platforms for the delivery of vaccines and immunotherapies. Future studies will focus on evaluating the lymphatic targeting and therapeutic potential of drug or vaccine-loaded polymers in pre-clinical disease models.

Investigation of the Role of Zirconia and Zirconia-containing Systems as Catalysts in Organic Transformations

Abstract: This review article discusses the applications of zirconia as a catalyst to promote various organic reactions and transformations. The article is subdivided into four main parts: 1) introduction, which consists of the history and introduction of zirconia, elaboration of its synthetic procedures, its application in various fields of science and technology with specified examples, and previously published review articles on ZrO2; 2) applications of sole zirconia and zirconia-based catalytic systems to promote various organic transformations, subdivided into oxidation reactions, hydrolysis and methanation reactions, reduction and hydrogenation reactions, furfural and synthesis of its derivatives, and miscellaneous reactions; 3) applications of sole zirconia and nano-sized ZrO2 to catalyze organic reactions and MCRs, classified as two-component reactions, three-component reactions (by a glance at pseudo 3-CRs), and four-component reactions (by a glance at pseudo 4-CRs); and 4) applications of zirconia-containing catalytic systems to catalyze organic transformations and MCRs classified as twocomponent reactions, three-component reactions, and four-component and higher-component reactions. According to investigations, some of the zirconia-based catalysts exist in nano-sized systems. Moreover, the literature survey contains publications up to the end of July 2023.

Comprehensive review of the skin use of bakuchiol: physicochemical properties, sources, bioactivities, nanotechnology delivery systems, regulatory and toxicological concerns

AbstractBakuchiol is a meroterpene that has recently aroused great interest in the cosmetic and pharmaceutical industries. Its main source is the seeds of Psoralea corylifolia, a medicinal plant native to Asia, despite having a wide geographical distribution. However, this medicinal herb faces endangerment due to low seed germination rates and high seedling mortality. In this context, this review article highlights studies that have focused on describing plant regeneration from root fragments. Subsequently, given its morphological similarity to other species, a technique that can be used to verify the authenticity of the plant and prevent counterfeiting is also mentioned and explored. Additionally, a “green” extraction method for obtaining bakuchiol is presented, and the possibility of obtaining bakuchiol through chemical synthesis routes is also explored. Furthermore, we provide an exhaustive description of bakuchiol's wide range of biological activities, with particular relevance to the skin. The main skin bioactivities of bakuchiol include antifungal, antibacterial, antioxidant, anti-inflammatory, antiaging, depigmenting, and anticancer. However, the particular physicochemical properties of bakuchiol require and benefit from the development of innovative skin delivery systems that allow its encapsulation. These include micro- and nano-sized systems for therapeutic and cosmetic applications, which are also carefully described in this review article. Finally, regulatory issues, metabolic considerations, and toxicological concerns related to the use of bakuchiol in cosmetic and dermopharmaceutical formulations will be addressed, relating not only to the user but also to the environment. Graphical abstract

A vivid outline demonstrating the benefits of exosome-mediated drug delivery in CNS-associated disease environments

The efficacy of drug delivery mechanisms has been improvised with time for different therapeutic purposes. In most cases, nano-sized delivery systems have been modeled over decades for the on-target applicability of the drugs. The use of synthetic drug delivery materials has been a common practice, although research has now focussed more on using natural vehicles, to avoid the side effects of synthetic delivery systems and easy acceptance by the body. Exosome is such a natural nano-sized vehicle that exceeds the efficiency of many natural vehicles, for being immune-friendly, due to its origin. Unlike, other natural drug delivery systems, exosomes are originated within the body's cells, and from there, they happen to travel through the extracellular matrices into neighboring cells. This capacity of exosomes has made them an efficient drug delivery system over recent years and now a large number of researches have been carried out to develop exosomes as natural drug delivery vehicles. Several experimental strategies have been practiced in this regard which have shown that exosomes are exclusively capable of carrying drugs and they can also be used in targeted delivery, for which they efficiently can reach and release the drug at their target cells for consecutive effects. One of the most interesting features of exosomes is they can cross the blood-brain barrier (BBB) in the body and hence, for the disease where other delivery vehicles are incapable of reaching the destination of the drug, exosomes can overcome the hurdle. This review particularly, focuses on the different aspects of using exosomes as a potential nano-sized drug delivery system for some of the severe diseases associated with the central nervous system of the human body.

Magnetic-assisted sequential templated self-assembly of hybrid colloid nanoparticle systems.

The assembly of hybrid nanoparticles is a pioneering route for developing nanoscale functional devices, enabling breakthroughs in various fields, including electronics, photonics, energy, sensing, and biomedical applications. Here, we focus on the templated assembly of nano-sized colloidal systems using a combination of silica-coated superparamagnetic beads (MBs) and polymer-coated gold nanoparticles (AuNPs) or silver nanoparticles (AgNPs). These hybrid nanoparticles introduce new functionalities that allow them to be used as nanomachines with numerous possible applications. Using sequential capillarity-assisted particle assembly (sCAPA), we deposit MBs with activating nano-transducers made of PNIPAm@AuNPs, which respond to specific external stimuli such as temperature variations. We deposit MBs with surface-enhanced Raman scattering (SERS) AgNPs, which have the ability to detect molecules at low concentrations. A key achievement of our study is demonstrating the successful CAPA assembly of nanoparticles with ingenious surface chemistry and retrieving these assembled structures from nanotraps in a liquid medium. This ability highlights the potential of hybrid colloids in precisely targeted drug delivery systems and highly effective mobile sensors. It represents a significant leap forward in using nanotechnology to create more complex and responsive nanoscale assemblies.

Polymer–drug conjugates as nano-sized multi-targeting systems for the treatment of Alzheimer's disease

This review mainly highlights the use of polymer–drug conjugates as an advanced drug delivery system to improve the treatment of AD and other neurodegenerative diseases.

Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni?

CLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology. We invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W. The novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of nanotechnology-based immunotherapy, not only for schistosomiasis, but also for other parasitic infections in which chemotherapy has been shown to be immune-dependent. The results propose that the immunodominant reactivity of the anti-SmI serum, Schistosoma mansoni fructose biphosphate aldolase, SmFBPA, merits serious attention as a therapeutic and vaccine candidate.

Development of a nano-size off-grid energy system using renewables and IoT technologies at the Meteoria visitor center: A Finnish case study

The increased utilization of non-renewable energy during the last century has influenced the climate, with increased carbon dioxide emissions and elevated temperature as a result. Thus, the need to develop and demonstrate new sustainable solutions regarding both energy supply and consumption, but also energy system optimization, is obvious. This case study presents the nano-size off-grid energy system at the Meteoria visitor center in Ostrobothnia, Finland, and the real-time measuring techniques that have been installed to follow up the energy production and consumption. The Meteoria consists of several buildings, which are open to the public from April to October. The case site is operated by energy derived from wind power, solar power, and a diesel generator (as a backup), with batteries for energy storage. The Internet of Things (IoT) has been retrofitted to the existing energy system to enable energy measurements and follow various electrical parameters in real-time. In addition, a graphical visualization platform open to the public has been developed. In this study, the completeness of data sampling and the IoT system was checked, and the results show high availability of data. Furthermore, various errors/limitations regarding the IoT system were identified. The energy supply/demand at the Meteoria in 2021 was monitored and the challenges regarding the existing energy system in a cold climate zone are discussed as well as the potential role of the Meteoria to function as a living lab.

Self emulsifying drug delivery system: norfloxacin model drug

Background Norfloxacin is a synthetic antibacterial fluoroquinolone that is poorly water soluble and active against a wide spectrum of gram-positive and gram-negative aerobic bacteria. The goal of this work was to create a self-nanoemulsion (SNE) as a colloidal dispersed drug delivery system for increasing norfloxacin dissolving rate, while also assuming intestinal lymphatic transport participation for such a nano-size system that would increase norfloxacin oral bioavailability. Methods Depending on the solubility of norfloxacin in various components, several formulations of liquid SNEDDS of the antibiotic were created using oleic acid (oil), tween20 (surfactant), and PEG200 (co-surfactant). To assess the presence of a nanoemulsion region, phase diagram was generated at various oil: surfactant: co-surfactant ratios. Results The in-vitro dissolution profile suggested an optimum norfloxacin SEDD formulation (F1) comprised of oleic acid (10%), tween 20 (45%), and PEG200 (45%), as opposed to commercially available traditional tablets. The F1 formula exhibited thermodynamic stability with a zeta potential of +60.78mV and a droplet size of 57.4nm. The F1 formula revealed an improved dissolving profile as compared to the commercial Tablet of norfloxacin. Conclusion Based on the findings, this study indicated that preparing norfloxacin as a liquid self-nanoemulsifying system improved the solubility and drug release of norfloxacin counteract the inconsistent bioavailability of the commercial tablet.

Revealing the Electrochemical Kinetics of Electrolytes in Nanosized LiFePO4 Electrodes

Lithium-ion battery rate performance is ultimately limited by the electrolyte, yet the behaviors of electrolytes during high-rate (dis)charge remain elusive to electrochemical measurement. Herein, we develop and study a nanosized LiFePO4 model system in which the electrolyte completely controls the electrochemical kinetics of the porous electrode. Impedance spectroscopy, cyclic voltammetry, and rate performance testing prove that ion transport in the electrolyte is the sole rate-limiting process, even in thin electrodes. A novel pseudo-steady-state extrapolation (S3E) method for Tafel analysis shows that LiFePO4 obeys Butler-Volmer kinetics with a transfer coefficient of 3. The combination of these unexpectedly rapid interfacial kinetics and an activation barrier for phase transformation causes extreme reaction heterogeneity, which manifests as a moving reaction zone. Resistance versus capacity analysis enables direct measurement of electrolyte resistance growth during high-rate (dis)charge, revealing how the interaction between concentration polarization and a moving reaction zone controls electrolyte rate performance in LiFePO4 electrodes. This work elucidates the profound impacts of the electrolyte on electrochemical measurements in porous battery electrodes: when the active material is not rate limiting, it is impossible to directly measure the intrinsic kinetics of the active material, but conversely, it becomes possible to directly measure the kinetics of the electrolyte.

Intracellular Fate of the Photosensitizer Chlorin e4 with Different Carriers and Induced Metabolic Changes Studied by 1H NMR Spectroscopy.

Porphyrinic photosensitizers (PSs) and their nano-sized polymer-based carrier systems are required to exhibit low dark toxicity, avoid side effects, and ensure high in vivo tolerability. Yet, little is known about the intracellular fate of PSs during the dark incubation period and how it is affected by nanoparticles. In a systematic study, high-resolution magic angle spinning NMR spectroscopy combined with statistical analyses was used to study the metabolic profile of cultured HeLa cells treated with different concentrations of PS chlorin e4 (Ce4) alone or encapsulated in carrier systems. For the latter, either polyvinylpyrrolidone (PVP) or the micelle-forming polyethylene glycol (PEG)-polypropylene glycol triblock copolymer Kolliphor P188 (KP) were used. Diffusion-edited spectra indicated Ce4 membrane localization evidenced by Ce4 concentration-dependent chemical shift perturbation of the cellular phospholipid choline resonance. The effect was also visible in the presence of KP and PVP but less pronounced. The appearance of the PEG resonance in the cell spectra pointed towards cell internalization of KP, whereas no conclusion could be drawn for PVP that remained NMR-invisible. Multivariate statistical analyses of the cell spectra (PCA, PLS-DA, and oPLS) revealed a concentration-dependent metabolic response upon exposure to Ce4 that was attenuated by KP and even more by PVP. Significant Ce4-concentration-dependent alterations were mainly found for metabolites involved in the tricarboxylic acid cycle and the phosphatidylcholine metabolism. The data underline the important protective role of the polymeric carriers following cell internalization. Moreover, to our knowledge, for the first time, the current study allowed us to trace intracellular PS localization on an atomic level by NMR methods.

Engineered Exosomes as Theranostic Platforms for Cancer Treatment.

Tremendous progress in nanotechnology and nanomedicine has made a significant positive effect on cancer treatment by integrating multicomponents into a single multifunctional nanosized delivery system for combinatorial therapies. Although numerous nanocarriers developed so far have achieved excellent therapeutic performance in mouse models via elegant integration of chemotherapy, photothermal therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy, their synthetic origin may still cause systemic toxicity, immunogenicity, and preferential detection or elimination by the immune system. Exosomes, endogenous nanosized particles secreted by multiple biological cells, could be absorbed by recipient cells to facilitate intercellular communication and content delivery. Therefore, exosomes have emerged as novel cargo delivery tools and attracted considerable attention for cancer diagnosis and treatment due to their innate stability, biological compatibility, and biomembrane penetration capacity. Exosome-related properties and functions have been well-documented; however, there are few reviews, to our knowledge, with a focus on the combination of exosomes and nanotechnology for the development of exosome-based theranostic platforms. To make a timely review on this hot subject of research, we summarize the basic information, isolation and functionalization methodologies, diagnostic and therapeutic potential of exosomes in various cancers with an emphasis on the description of exosome-related nanomedicine for cancer theranostics. The existing appealing challenges and outlook in exosome clinical translation are finally introduced. Advanced biotechnology and nanotechnology will definitely not only promote the integration of intrinsic advantages of natural nanosized exosomes with traditional synthetic nanomaterials for modulated precise cancer treatment but also contribute to the clinical translations of exosome-based nanomedicine as theranostic nanoplatforms.

Graded oxide layer for high-performing nanosized synaptic emulator

The close emulation of synaptic plasticity in a nanosized memristive system using a single functional layer is crucial for high-performance neuromorphic computing. Here, we investigate a novel and adaptive approach to constructing a single layer-based nanosized synaptic emulator. The top surface of a reactive Ti metal layer is selectively transformed into an ultra-thin oxide functional layer (TiOx) by adding the oxygen in a controlled manner using a plasma fireball-based low-energy ion implanter to fabricate the device. Composition gradient-based oxygen vacancy distribution produced in the active layer and their dynamics for driving bias voltage exhibit conductivity modulation. Fundamental and essential characteristics of bio-synapse, such as long-term potentiation and depression and spike rate-dependent synaptic plasticity, are confirmed at the nanoscale by employing conductive atomic force microscopy. The synaptic weight reversal in the advanced Bienenstock-Cooper-Munro learning rule is demonstrated to satisfy the need to assemble nanosized artificial synapses that mimic the various bio-functions approximately. The forming-free ability and low operating current of the device evident their potential in building power-efficient neuromorphic systems. Benefiting from the simple and cheap fabrication method of the device and excellent emulation of bio-synaptic functions offers a robust path to develop the high-performance neuromorphic architecture.

Exploring Nanocarriers as Treatment Modalities for Skin Cancer.

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.