Pattern recognition of multiple metal ions using fluorescent Perylenyl nanoaggregates and application in food traceability.

Metal ions (MIs) identification is essential for the safety assessment, traceability and authentication of food. Most current approaches for detecting MIs are difficult to reconcile the simplicity, sensitivity and stability simultaneously. In this work, we proposed a novel strategy for discriminating MIs based on fluorescent supramolecular nanoaggregates (SNAs). In the presence of MI, perylene diimide derivatives (PDI)-based SNAs could be formed through the multiple non-covalent interactions between them including electrostatic, coordination and π-π interactions. With the assistance of discriminant analysis (LDA), different MIs (Hg2+, Ag+, Cd2+, Fe3+, Cr3+, Fe2+, Zn2+, Cu2+ and Pb2+) were successfully identified at three different concentration levels. It featured good quantitative sensing abilities in buffer solutions and practical samples. Furthermore, a water-quality evaluation model was successfully constructed for the distinction of different sources of drinking water, and the fluorescence array sensor technology was applied for the first time to the geographical traceability of apples.

Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35 mg kg-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

Excellent Electroluminescent Property of Eu3+-Induced Polystyrene-co-poly(acrylic acid) Aggregates (EIPAs) in Polymeric Light-Emitting Diodes.

Eu3+-induced polystyrene-co-poly(acrylic acid) aggregates (EIPAs) were synthesized using a self-assembly approach, and their structures and photophysical characteristics were examined to achieve effective monochromatic red emission in polymer light-emitting diodes (PLEDs). By adjusting the monomer ratio in RAFT polymerization, the size of Eu3+-induced block copolymer nanoaggregates can be regulated, thereby modulating the luminescence intensity. High-performance bilayer polymer light-emitting devices were fabricated using poly(9,9-dioctylfluorene) (PFO) and 2-(tert-butylphenyl)-5-biphenylyl-1,3,4-oxadiazole (PBD) as the host matrix, with EIPAs as the guest dopant. The devices exhibited narrow red emission at 615 nm with a full width at half-maximum (fwhm) of 15 nm across doping concentrations of 1, 3, 5, and 10 wt %. At a doping concentration of 3 wt %, the device achieved a maximum brightness of 1864.48 cd/m2 at 193.82 mA/cm2 and an external quantum efficiency of 3.20% at a current density of 3.5 mA/cm2. These results indicate that incorporating polystyrene-co-poly(acrylic acid) with Eu3+ complexes enhances the excitation and emission intensity, as well as the structural stability of the emitting layer in PLEDs, thereby improving the device performance.

Heterocyclic Hemipiperazines: Multistimuli-Responsive Switches and Sensors for Zinc or Cadmium Ions.

Advance in the design of molecular photoswitches - adapters that convert light into changes at molecular level - opens up exciting possibilities in preparing smart polymers, drugs photoactivated inside humans, or light-fueled nanomachines that might in the future operate in our bloodstream. Hemipiperazines are recently reported biocompatible molecular photoswitches based on cyclic dipeptides. Here we report a multistimuli-responsive hemipiperazine-based switch that reacts on light, solvents, acidity, or metal ions. Its photoequilibration is controlled by the intramolecular hydrogen bonding pattern. The compound can be used as a mid-nanomolar photoswitchable fluorescent sensor for zinc and cadmium ions, applicable to monitor environmental pollution in real time.

Regulating interparticle proximity in plasmonic nanosphere aggregates to enhance photoacoustic response and photothermal stability.

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near-infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agent for PA imaging. Silver (Ag), among plasmonic metals, is particularly attractive due to its strongest optical response and highest heat conductivity. Our results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody-like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, our AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high-contrast PA imaging over multiple imaging sessions. Furthermore, we demonstrate the capability of the AgNAs for molecular PA cancer imaging in vivo by incorporating a tumor-targeting peptide moiety.

Customizable Fabrication of Photothermal Microneedles with Plasmonic Nanoparticles Using Low-Cost Stereolithography Three-Dimensional Printing.

Photothermal microneedle (MN) arrays have the potential to improve the treatment of various skin conditions such as bacterial skin infections. However, the fabrication of photothermal MN arrays relies on time-consuming and potentially expensive microfabrication and molding techniques, which limits their size and translation to clinical application. Furthermore, the traditional mold-and-casting method is often limited in terms of the size customizability of the photothermal array. To overcome these challenges, we fabricated photothermal MN arrays directly via 3D-printing using plasmonic Ag/SiO2 (2 wt % SiO2) nanoaggregates dispersed in ultraviolet photocurable resin on a commercial low-cost liquid crystal display stereolithography printer. We successfully printed MN arrays in a single print with a translucent, nanoparticle-free support layer and photothermal MNs incorporating plasmonic nanoaggregates in a selective fashion. The photothermal MN arrays showed sufficient mechanical strength and heating efficiency to increase the intradermal temperature to clinically relevant temperatures. Finally, we explored the potential of photothermal MN arrays to improve antibacterial therapy by killing two bacterial species commonly found in skin infections. To the best of our knowledge, this is the first time describing the printing of photothermal MNs in a single step. The process introduced here allows for the translatable fabrication of photothermal MN arrays with customizable dimensions that can be applied to the treatment of various skin conditions such as bacterial infections.

Boosting antigen-specific T cell activation with lipid-stabilized protein nanoaggregates.

Vaccines based on protein antigens have numerous advantages over inactivated pathogens, including easier manufacturing and improved safety. However, purified antigens are weakly immunogenic, as they lack the spatial organization and the associated 'danger signals' of the pathogen. Formulating vaccines as nanoparticles enhances the recognition by antigen presenting cells, boosting the cell-mediated immune response. This study describes a nano-precipitation method to obtain stable protein nanoaggregates with uniform size distribution without using covalent cross-linkers. Nanoaggregates were formed via microfluidic mixing of ovalbumin (OVA) and lipids in the presence of high methanol concentrations. A purification protocol was set up to separate the nanoaggregates from OVA and liposomes, obtained as byproducts of the mixing. The nanoaggregates were characterized in terms of morphology, ζ-potential and protein content, and their interaction with immune cells was assessed in vitro. Antigen-specific T cell activation was over 6-fold higher for nanoaggregates compared to OVA, due in part to the enhanced uptake by immune cells. Lastly, a two-dose immunization with nanoaggregates in mice induced a significant increase in OVA-specific CD8+ T splenocytes compared to soluble OVA. Overall, this work presents for the first time the microfluidic production of lipid-stabilized protein nanoaggregates and provides a proof-of-concept of their potential for vaccination.

Hot-water soluble fraction of starch as particle-stabilizers of oil-in-water emulsions: Effect of dry heat modification.

Dry heat treatment (DHT) ranging from 130 to 190 °C was employed to modify corn starch. The hot-water soluble fraction (HWS) of the DHT-modified starch was isolated, and its capacity and mechanism for stabilizing O/W emulsions were investigated. Corn starch underwent a significant structural transformation by DHT at 190 °C, characterized by a 7.3 % reduction in relative crystallinity, a tenfold decrease in weight-average molecular weight from 95.21 to 8.11 × 106 g/mol, and a degradation of over one-third of the extra-long chains of amylopectin (DP > 36) into short chains (DP 6-12). These structural modifications resulted in a substantial formation of soluble amylopectin, leading to a sharp increase in the HWS content of corn starch from 3.16 % to 85.06 %. This augmented HWS content surpassed the critical macromolecule concentration, prompting the formation of HWS nanoaggregates. These nanoaggregates, with an average particle size of 33 nm, functioned as particle stabilizers, ensuring the stability of the O/W emulsion through the Pickering mechanism. The O/W emulsion stabilized by HWS nanoaggregates exhibited noteworthy centrifugal and storage stability, with rheological properties remaining nearly unchanged over a storage period of 180 days. Given its straightforward preparation process, the HWS of DHT-modified starch could be a promising natural emulsifier.

Inhaled JAK Inhibitor GDC-0214 Nanoaggregate Powder Exhibits Improved Pharmacokinetic Profile in Rats Compared to the Micronized Form: Benefits of Thin Film Freezing.

Asthma is a common chronic disease affecting the airways in the lungs. The receptors of allergic cytokines, including interleukin (IL)-4, IL-5, and IL-13, trigger the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, which involves the pathogenesis of asthma. GDC-0214 is a JAK inhibitor that was developed as a potent and selective target for the treatment of asthma, specifically targeting the lungs. While inhaled GDC-0214 is a promising novel treatment option against asthma, improvement is still needed to achieve increased potency of the powder formulation and a reduced number of capsules containing powder to be inhaled. In this study, high-potency amorphous powder formulations containing GDC-0214 nanoaggregates for dry powder inhalation were developed using particle engineering technology, thin film freezing (TFF). A high dose per capsule was successfully achieved by enhancing the solubility of GDC-0214 and powder conditioning. Lactose and/or leucine as excipients exhibited optimum stability and aerosolization of GDC-0214 nanoaggregates, and aerosolization of the dose was independent of air flow through the device between 2 and 6 kPa pressure drops. In the rat PK study, formulation F20, which contains 80% GDC-0214 and 20% lactose, resulted in the highest AUC0-24h in the lungs with the lowest AUC0-24h in the plasma that corresponds to a 4.8-fold higher ratio of the lung-to-plasma exposures compared to micronized crystalline GDC-0214 powder administered by dry powder inhalation. Therefore, GDC-0214 nanoaggregates produced by TFF provided an improved dry powder for inhalation that can lead to enhanced therapeutic efficacy with a lower risk of systemic toxicity.

Rejuvenating Hyaline Cartilaginous Phenotype of Dedifferentiated Chondrocytes in Collagen II Scaffolds: A Mechanism Study Using Chondrocyte Membrane Nanoaggregates as Antagonists.

Joint cartilage lesions affect the global population in the current aging society. Maintenance and rejuvenation of articular cartilage with hyaline phenotype remains a challenge as the underlying mechanism has not been completely understood. Here, we have designed and performed a mechanism study using scaffolds made of type II collagen (Col2) as the 3D cell cultural platforms, on some of which nanoaggregates comprising extracts of chondrocyte membrane (CCM) were coated as the antagonist of Col2. Dedifferentiated chondrocytes were, respectively, seeded into these Col2 based scaffolds with (antCol2S) or without (Col2S) CCM coating. After 6 weeks, in Col2S, the chondrocytes were rejuvenated to regain hyaline phenotype, whereas this redifferentiation effect was attenuated in antCol2S. Transcriptomic and proteomic profiling indicated that the Wnt/ß-catenin signaling pathway, which is an opponent to maintenance of the hyaline cartilaginous phenotype, was inhibited in Col2S, but it was contrarily upregulated in antCol2S due to the antagonism and shielding against Col2 by the CCM coating. Specifically, in antCol2S, since the coated CCM nanoaggregates contain the same components as those present on the surface of the seeded chondrocytes, the corresponding ligand sites on Col2 had been preoccupied and saturated by CCM coating before exposure to the seeded cells. The results indicated that the ligation between Col2 ligands and integrin α5 receptors on the surface of the seeded chondrocytes in antCol2S was antagonized by the CCM coating, which facilitates the Wnt/ß-catenin signaling toward the loss of hyaline cartilaginous phenotype. This finding reveals the contribution of Col2 for maintenance and rejuvenation of the hyaline cartilaginous phenotype in chondrocytes.

Aggregation-induced emission carbon dots as Al3+-mediated nanoaggregate probe for rapid and selective detection of tetracycline.

Worldwide abuse of tetracycline (TC) seriously threatens environmental safety and human health. Metal-TC complexes formed by residual TC in the environment can also contribute to the spread of antibiotic resistance. Therefore, monitoring of TC residues is still required. Here, we report novel aggregation-induced emission carbon dots (AIE-Cdots) as nanoaggregate probes for the rapid and selective detection of TC residue. Riboflavin precursors with rotational functional groups led to the development of AIE-Cdots. The aggregation of AIE-Cdots was induced selectively for Al3+, amplifying the fluorescence signals owing to the restricted rotation of the side chains on the AIE-Cdot surface. The fluorescence signal of such Al3+-mediated nanoaggregates (Al3+-NAs) was further triggered by the structural fixation of TC at the Al3+ active sites, suggesting the formation of TC-coordinated Al3+-NAs. A linear correlation was observed in the TC concentration range of 0-10 µM with a detection limit of 42 nM. In addition, the strong Al3+ binding affinity of AIE-Cdots produced similar NAs and enhanced fluorescence signals in Al3+-TC mixtures. These AIE-Cdots-based nanoplatforms have a rapid response, good selectivity, and reliable accuracy for detecting TC or aluminum complexes, meeting the requirements for hazardous substance monitoring and removal in environmental applications.

Berberine-phospholipid nanoaggregate-embedded thiolated chitosan hydrogel for aphthous stomatitis treatment.

Aim: This study aimed to develop nanoaggregates of berberine-phospholipid complex incorporated into thiolated chitosan (TCS) hydrogel for the treatment of aphthous stomatitis. Methods: The berberine-phospholipid complex was formulated through the solvent evaporation technique and assembled into nanoaggregates. TCS was synthesized through the attachment of thioglycolic acid to chitosan (CS). Nanoaggregates-TCS was prepared by the incorporation of nanoaggregates into TCS and underwent in vitro and in vivo tests. Results: Nanoaggregates-TCS exhibited prolonged release of berberine. The mucoadhesive strength of nanoaggregates-TCS increased 1.75-fold compared with CS hydrogel. In vivo studies revealed the superior therapeutic efficacy of nanoaggregates-TCS compared with that of other groups. Conclusion: Due to prolonged drug release, appropriate residence time and anti-inflammatory effects, nanoaggregates-TCS is an effective system for the treatment of aphthous stomatitis.

Stimuli-responsive aggregation-induced emission of molecular probes by electrostatic and hydrophobic interactions: Effect of organic solvent content and application for probing of alkaline phosphatase activity.

We suggest that aggregation-induced emission (AIE) molecular probes with single charged/reactive group can exist in the formation of nanostructures but not monomers at extremely low organic solvent content. The nanoaggregates show good dispersivity and emit week emission. Stimuli-responsive assembly of nanoaggregates by electrostatic interactions can turn on the fluorescence, facilitating the design of biosensors with single-charged molecular probes as the AIE fluorogens. To prove the concept, tetraphenylethene-substituted pyridinium salt (TPE-Py) was used as the AIE fluorogen for probing of alkaline phosphatase (ALP) activity with pyrophosphate ion (PPi) as the enzyme substrate. The dynamic light scattering and transmission electron microscope experiments demonstrated that TPE-Py probes existed in aqueous solution at nanometer size and morphology. Stimuli such as the negatively charged PPi, citrate, ATP, ADP, NADP and DNA could trigger the aggregation of the positively charged TPE-Py nanoparticles, thus enhancing the fluorescence via AIE effect. ALP-enzymatic hydrolysis of PPi into two phosphate ions (Pi) limited the aggregation of TPE-Py nanoparticles. The strategy was used for the assay of ALP with a low detection limit (1 U/L) and wide linear range (1-200 U/L). We also investigated the effect of organic solvent content on the AIE process and found that high concentration of organic solvent can prevent the hydrophobic interaction between AIE molecules but show no essential influence on the electrostatic interaction-mediated assembly. The work should be evaluable for understanding AIE phenomenon and developing novel, simple and sensitive biosensors using a molecular probe with single charged/reactive group as the signal reporter.

Triple Hydrophilic Statistical Terpolymers via RAFT Polymerization: Synthesis and Properties in Aqueous Solutions.

In this work, we report the synthesis of novel triple hydrophilic statistical terpolymers consisting of three different methacrylate monomers with varying degrees of responsivity to solution conditions. Terpolymers of the type poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA), and of different compositions, were prepared by using the RAFT methodology. Their molecular characterization was carried out using size exclusion chromatography (SEC) and spectroscopic techniques, including 1H-NMR and ATR-FTIR. Studies in dilute aqueous media by dynamic and electrophoretic light scattering (DLS and ELS) show their potential responsiveness regarding changes in temperature, pH, and kosmotropic salt concentration. Finally, the change in hydrophilic/hydrophobic balance of the formed terpolymer nanoparticles during heating and cooling was studied using fluorescence spectroscopy (FS) in conjunction with pyrene giving additional information on the responsiveness and internal structure of the self-assembled nanoaggregates.

Etoposide-Entrapped Progesterone-Cationic Lipid Nanoaggregates as Selective Therapeutics against Etoposide-Resistant Colorectal Cancer Cells.

Drug resistance has a major impact on the treatment of several cancers. This is mainly due to the overexpression of cellular drug efflux proteins. Hence, drug-delivery systems that can avoid this resistance are needed. We report PR10, a progesterone-cationic lipid conjugate, as a self-assembling nanoaggregate that delivers a drug cargo of etoposide, a topoisomerase inhibitor, selectively to cancer cells. In this study, we observed that etoposide nanoaggregates (P : E) caused selective and enhanced toxicity in etoposide-resistant CT26 cancer cells (IC50 9 µM) compared to when etoposide (IC50 >20 µM) was used alone. Concurrently, no toxicity was observed in etoposide-sensitive HEK293 cells for P : E treatment (IC50 >20 µM). The P : E-treated cancer cells seem to have no effect on ABCB1 expression, but etoposide-treated cells exhibited a twofold increase in ABCB1 expression, a potent efflux protein for several xenobiotic compounds. This observation supports the notion that the enhanced toxicity of P : E nanoaggregates is due to their ability to keep the expression of ABCB1 low, thus allowing longer intracellular residence of etoposide. In a BALB/c orthotopic colorectal cancer model, the nanoaggregates led to enhanced survival (45 days) compared to etoposide-treated mice (39 days). These findings suggest that PR10 could be used as a potential cancer-selective etoposide delivery vehicle to treat several etoposide-resistant cancers with fewer side effects due to the nonspecific toxicity of the drug.

Design of One-for-All Near-Infrared Aggregation-Induced Emission Nanoaggregates for Boosting Theranostic Efficacy.

Fluorescence-guided phototherapy, including photodynamic and photothermal therapy, is considered an emerging noninvasive strategy for cancer treatments. Organic molecules are promising theranostic agents because of their facile construction, simple modification, and good biocompatibility. Organic systems that integrated multifunctionalities in a single component and achieved high efficiency in both imaging and therapies are rarely reported as the inherently competitive energy relaxation pathways are hard to modulate, and fluorescence quenching occurs upon molecular aggregation. Herein, a versatile theranostic platform with near-infrared emission, high fluorescence quantum yield, robust reactive oxygen species production, and excellent photothermal conversion efficiency was developed based on an aggregation-induced emission luminogen, namely, TPA-TBT. In vivo studies revealed that the TPA-TBT nanoaggregates exhibit outstanding photodynamic and photothermal therapy efficacy to ablate tumors inoculated in a mouse model. This work offers a design strategy to develop one-for-all cancer theranostic agents by modulating and utilizing the relaxation energy of excitons in full.

Size-controllable colloidal Ag nano-aggregates with long-time SERS detection window for on-line high-throughput detection.

Making metal nanoparticle aggregates is a common way to improve surface-enhanced Raman scattering (SERS) enhancement via the formation of hot spots between nanoparticles. Here, we propose a "freeze-thaw-ultrasonication" method to obtain stable colloidal Ag nano-aggregates (AgNAs) with controllable sizes, which can remain stable for a few days. Compared with other method using aggregation reagents (e.g., organic molecules and salt), this method can maintain metal surface charges and adsorption affinity, which ensures the excellent SERS stability and sensitivity. The SERS detection window during the experiment can reach more than 25 min, which makes it a prerequisite for accurate SERS detection during a long-time range. Combining the obtained stable AgNAs with microfluidic devices, we established a sequential SERS on-line continuous detection method for the high-throughput detection of multiplex samples. The UV-Fenton degradation process of methylene blue (MB) is continuously on-line monitored through this platform, which is more sensitive than the UV-Vis Spectrum. Moreover, we have realized the sensitive and accurate detection of 5-nitro-8-hydroxyquinoline (5-NQ) with antibacterial and anticancer activities based on chloride-functionalized silver, which paved a way for SERS high-throughput analysis in bioanalysis and other fields.

Mineral Nanoparticle Aggregation Alters Contaminant Transport under Flow.

Iron oxyhydroxide nanoparticle reactivity has been widely investigated, yet little is still known on how particle aggregation controls the mobility and transport of environmental compounds. Here, we examine how aggregates of goethite (α-FeOOH) nanoparticle deposited on 100-300 µm quartz particles (GagCS) alter the transport of two emerging contaminants and two naturally occurring inorganic ligands-silicates and phosphates. Bromide tracer experiments showed no water fractionation into mobile and immobile water zones in an individual goethite-coated sand (GCS) column, whereas around 10% of the total water was immobile in a GagCS column. Reactive compounds were, in contrast, considerably more mobile and affected by diffusion-limited processes. A new simulation approach coupling the mobile-immobile equation with surface complexation reactions to surface reactive sites suggests that ∼90% of the binding sites were likely within the intra-aggregate zones, and that the mass transfer between mobile and immobile fractions was the rate-limited step. The diffusion-controlled processes also affected synergetic and competitive binding, which have otherwise been observed for organic and inorganic compounds at goethite surfaces. These results thereby call for more attention on transport studies, where tracer or conservative tests are often used to describe the reactive transport of environmentally relevant molecules.

Magnetophoretic Intranasal Drug-loaded Magnetic Nano-aggregates as a Platform for Drug Delivery in Status Epilepticus.

BACKGROUND: Status epilepticus is associated with substantial morbidity and neuronal necrosis, and the duration of the seizure would affect its following complications. Eliminating the duration would have valuable outcomes; however, the presence of BBB is an obstacle. The purpose of the current study was to achieve a nose-to-brain magnetic drug delivery system to accelerate the onset of action, and to reduce the mucociliary clearance via implementing the magnetic field. MATERIALS AND METHODS: The drug-entrapped magnetic nanoaggregates were prepared via a 2-step method, synthesis of the magnetic nanoparticles and drug loading. Optimization of the variables, including ammonium hydroxide:water ratio, beta-cyclodextrin%, duration of the mixing time, amount of Pluronic, and drug:magnetic nanoaggregates mass ratio was performed according to particle size, PDI, zeta potential, release profile and entrapment efficiency. The efficacy of optimized formulation was assessed in the animal model. RESULTS: According to the analysis performed by the software, drug-to-nanoparticle ratio and the duration of mixing time were found to be significantly effective (p < 0.05) for entrapment efficiency and particle size distribution, respectively. The optimum formulation with an approximate average size of 581 nm and 61% entrapment efficiency was obtained, which released about 80% of its drug content within the first 20 minutes. The in vivo efficacy was significantly improved (p < 0.05) by administration of magnetic nanoaggregates in the presence of a simple external magnet placed on the glabellar region of the animals, compared to the control groups. CONCLUSION: This drug delivery system could be suggested as a fast-acting alternative for seizure cessation in status epilepticus emergencies.

Carrier-free nanoplatforms from natural plants for enhanced bioactivity.

BACKGROUND: Natural plants as well as traditional Chinese medicine have made outstanding contributions to the health and reproduction of human beings and remain the basis and major resource for drug innovation. Carrier-free nanoplatforms completely self-assembled by pure molecules or therapeutic components have attracted increasing attention due to their advantages of improved pharmacodynamics/pharmacokinetics, reduced toxicity, and high drug loading. In recent years, carrier-free nanoplatforms produced by self-assembly from natural plants have contributed to progress in a variety of therapeutic modalities. Notably, these nanoplatforms based on the interactions of components from different natural plants improve efficiency and depress toxicity. AIM OF REVIEW: In this review, different types of self-assembled nanoplatforms are first summarized, mainly including nanoassemblies of pure small molecules isolated from different plants, extracellular vesicles separated from fresh plants, charcoal nanocomponents obtained from charred plants, and nanoaggregates from plants formulae decoctions. Key Scientific Concepts of Review: We mainly focus on composition, self-assembly mechanisms, biological activity and modes of action. Finally, a future perspective of existing challenges with respect to the clinical application of plant-based carrier-free nanoplatforms is discussed, which may be instructive to further develop effective carrier-free nanoplatforms from natural plants in the future.