In Vivo Biodistribution, Clearance, and Biocompatibility of Multiple Carbon Dots Containing Nanoparticles for Biomedical Application

Current research on the use of carbon dots for various biological systems mainly focuses on the single carbon dots, while particles that contain multiple carbon dots have scarcely been investigated. Here, we assessed multiple carbon dots-crosslinked polyethyleneimine nanoparticles (CDs@PEI) for their in vivo biodistribution, clearance, biocompatibility, and cellular uptake. The in vivo studies demonstrate three unique features of the CDs@PEI nanoparticles: (1) the nanoparticles possess tumor-targeting ability with steady and prolonged retention time in the tumor region. (2) The nanoparticles show hepatobiliary excretion and are clear from the intestine in feces. (3) The nanoparticles have much better biocompatibility than the polyethyleneimine passivated single carbon dots (PEI-CD). We also found that pegylated CDs@PEI nanoparticles can be effectively taken up by the cells, which the confocal laser scanning microscope can image under different excitation wavelengths (at 405, 488, and 800 nm). These prior studies provide invaluable information and new opportunities for this new type of intrinsic photoluminescence nanoparticles in carbon dot-based biomedical applications.

Preparation of Polyetherimide Nanoparticles by a Droplet Evaporation-Assisted Thermally Induced Phase-Separation Method

The droplet evaporation effect on the preparation of polyetherimide (PEI) nanoparticles by thermally induced phase separation (TIPS) was studied. PEI nanoparticles were prepared in two routes. In route I, the droplet evaporation process was carried out after TIPS. In route II, the droplet evaporation and TIPS processes were carried out simultaneously. The surface tension and shape parameters of samples were measured via a drop shape analyzer. The Z-average particle diameter of PEI nanoparticles in the PEI/dimethyl sulfoxide solution (DMSO) suspension at different time points was tested by dynamic light scattering, the data from which was used to determine the TIPS time of the PEI/DMSO solution. The natural properties of the products from both routes were studied by optical microscope, scanning electron microscope and transmission electron microscope. The results show that PEI nanoparticles prepared from route II are much smaller and more uniform than that prepared from route I. Circulation flows in the droplet evaporation were indirectly proved to suppress the growth of particles. At 30 °C, PEI solid nanoparticles with 193 nm average particle size, good uniformity, good separation and good roundness were obtained. Route I is less sensitive to temperature than route II. Samples in route I were still the accumulations of micro and nanoparticles until 40 °C instead of 30 °C in route II, although the particle size distribution was not uniform. In addition, a film structure would appear instead of particles when the evaporation temperature exceeds a certain value in both routes. This work will contribute to the preparation of polymer nanoparticles with small and uniform particle size by TIPS process from preformed polymers.

Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy

Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.

Delivery of MicroRNA-let-7c-5p by Biodegradable Silica Nanoparticles Suppresses Human Cervical Carcinoma Cell Proliferation and Migration

Human cervical cancer is the most common gynecological malignancy. The continuous development of nanotechnology has allowed the wide use of nanomaterials in cancer treatment. Nanoparticles can be used as gene carriers because of their surface effect and small-size effect. MicroRNA-let-7c-5p (miR-let-7c-5p) belongs to the let-7 family. Although it has been reported to exert a tumor suppressive effect in a variety of cancers, the exact role and mechanism of miR-let-7c-5p in the progression of cervical cancer are unclear. In this study, we synthesized flower-shaped SiO2 –PEI nanoparticles with high pDNA/siRNA loading rates. This nanoparticle with miR-let-7c-5p-expressed plasmid could effectively transfer miR-let-7c-5p to human epithelial carcinoma (HeLa) cells. In addition, the combination of nanomaterials and gene therapy could inhibit the development of cancer under the conditions of extremely low cytotoxicity. These findings provided a new anticancer strategy based on F-SiO2 -polyethyleneimine/miR-let-7c-5p (FSP-let-7c-5p)nanoparticles and indicated that miR-let-7c-5p/IGF-1R/PI3K/AKT and -catenin/SLUG could be used as new potential targets for the treatment of cervical cancer.

Nanoparticles of Quaternary Ammonium Polyethylenimine Derivatives for Application in Dental Materials

Various quaternary ammonium polyethylenimine (QA-PEI) derivatives have been synthesized in order to obtain nanoparticles. Due to their antibacterial activity and non-toxicity towards mammalian cells, the QA-PEI nanoparticles have been tested extensively regarding potential applications as biocidal additives in various dental composite materials. Their impact has been examined mostly for dimethacrylate-based restorative materials; however, dental cements, root canal pastes, and orthodontic adhesives have also been tested. Results of those studies showed that the addition of small quantities of QA-PEI nanoparticles, from 0.5 to 2 wt.%, led to efficient and long-lasting antibacterial effects. However, it was also discovered that the intensity of the biocidal activity strongly depended on several chemical factors, including the degree of crosslinking, length of alkyl telomeric chains, degree of N-alkylation, degree of N-methylation, counterion type, and pH. Importantly, the presence of QA-PEI nanoparticles in the studied dental composites did not negatively impact the degree of conversion in the composite matrix, nor its mechanical properties. In this review, we summarized these features and functions in order to present QA-PEI nanoparticles as modern and promising additives for dental materials that can impart unique antibacterial characteristics without deteriorating the products’ structures or mechanical properties.

Cochlear Transfection Gene Guinea Pigs Mediates Atoh1-EGFP Based Hyaluronic Acid Modified Polyethyleneimine Nanoparticles

To modify polyethyleneimine (PEI) nanoparticles using hyaluronic acid (HA) to prepare a novel nonviral vector and use it to coat Atoh1-EGFP plasmid to detect its translocation in living guinea pig cochlea dyeing efficiency. Atoh1-EGFP plasmid was extracted and characterized using a Zetasizer particle size analyzer. HA/PEI/DNA complexion was characterized and introduced into the round window membrane. EGFP green fluorescence carried in the Atoh1 plasmid was observed by confocal microscopy. The transfection results were verified by Western blot and reverse transcription polymerase chain reaction (RT-PCR) from the perspective of protein and nucleic acid to verify its expression results. In this study, HA-modified PEI nanoparticles are negatively-charged nanoscale gene carrier complexes. After the Atoh1-EGFP plasmid was introduced into the cochlea, the results of confocal microscopy showed that the inner and outer hair cells of the basement membrane could be detected in green fluorescent protein. The transfection efficiency of basement membrane is as high as 81.7±4.71%, while the transversion is 33.8±9.02%. Western Blot and RT-PCR also confirmed that the Atoh1 gene can be successfully transfected on the basement membrane. The gene transfection of cochlea may be achieved by HA-modified PEI nanoparticle gene vector with no obvious toxicity to basement membrane cells. It is also an ideal inner-end gene transfection vector owing to its simple synthesis method and low cost.

Highly Adhesive and Sustainable UV/Heat Dual-Curable Adhesives Embedded with Reactive Core-Shell Polymer Nanoparticles for Super-Narrow Bezel Display

To achieve the seamless characteristics of displays, liquid crystal (LC) devices need a super-narrow bezel design. This device architecture can be constructed using functional adhesives that possess excellent physical and chemical properties. In this study, mechanically robust ultraviolet (UV)/heat dual-curable adhesives with outstanding reliability and processability have been fabricated using reactive poly(methyl methacrylate) (PMMA)/polyethyleneimine (PEI) core-shell nanoparticles. Their curing characteristics, narrow drawing processability, adhesive strength, elongation at break, and the contact contamination of LCs have been investigated. Compared to conventional adhesive material, the proposed adhesive containing multifunctional PMMA/PEI nanoparticles afforded a high adhesion strength of 40.2 kgf cm−2 and a high elongation of 64.8% due to the formation of a firm crosslinked network with matrix resins comprising bisphenol A epoxy resin and bisphenol A glycerolate dimethacrylate. Moreover, the proposed adhesive showed an excellent narrow drawing width of 1.2 mm, which is a prerequisite for super-narrow bezel display. With regard to LC contamination, it was found that the level of contamination could be remarkably reduced to 61 µm by a high-temperature curing process. This study makes a significant contribution to the development of advanced display, because it provides robust and sustainable display adhesives based on nanomaterials, thereby enhancing the life and sustained operability of displays.