Polyethyleneimine-functionalized magnetic sugarcane bagasse cellulose film for the efficient adsorption of ibuprofen.

Polyethyleneimine-modified magnetic sugarcane bagasse cellulose film (P-SBC/Fe3O4 film) was simply fabricated for the removal of ibuprofen (IBP), a typical emerging organic contaminant. The P-SBC/Fe3O4 film exhibited an equilibrium adsorption amount of 370.52 mg/g for IBP and a corresponding removal efficiency of 92.63 % under following adsorption conditions: 318 K, pH 4, and 0.25 mg/mL dosage. Thermodynamic studies indicated that adsorption of IBP on the P-SBC/Fe3O4 film was spontaneous (∆G < 0) and endothermic (∆H > 0). The adsorption data conformed to the Freundlich isotherm model and multilayer adsorption model (two layers), and an average of 3-4 active sites on the P-SBC/Fe3O4 film share an IBP molecule. Both the EDR-IDR and AOAS models vividly described the dynamic characteristics of adsorption process. Model fitting results, theoretical calculations, and comprehensive characterization revealed that adsorption is driven by electrostatic interactions between the primary amine of P-SBC/Fe3O4 film and the carboxyl group of IBP molecule, while other weak interactions are also non-ignorable. Furthermore, quantitative calculations based on density functional theory (DFT) underscored the importance of PEI functionalization. In conclusion, P-SBC/Fe3O4 film is an environmentally friendly and cost-effective adsorbent with significant potential for effectively removing IBP, while maintaining its efficacy over multiple cycles.

Amino-functionalized cellulose composite for efficient simultaneous adsorption of tetracycline and copper ions: Performance, mechanism and DFT study.

A novel cellulose composite (denoted as PEI@MMA-1) with porous interconnected structure was prepared by adsorbing methyl cellulose (MC) onto microcrystalline cellulose (MCC) and cross-linking polyethyleneimine (PEI) with MCC by the action of epichlorohydrin, which had the excellent adsorption property, wettability and elasticity. The performances of PEI@MMA-1 composite for removing tetracycline (TC), Cu2+ and coexistent pollutant (TC and Cu2+ mixture) were systematically explored. For single TC or Cu2+ contaminant, the maximum adsorption capacities were 75.53 and 562.23 mg/g at 30 °C, respectively, while in the dual contaminant system, they would form complexes and Cu2+ could play a "bridge" role to remarkably promote the adsorption of TC with the maximum adsorption capacities of 281.66 and 253.58 mg/g for TC and Cu2+. In addition, the adsorption kinetics, isotherms and adsorption mechanisms of single-pollutant and dual-pollutant systems have been thoroughly investigated. Theoretical calculations indicated that the amide group of TC molecule with the assistance of Cu2+ interacted with the hydroxyl group of PEI@MMA-1 composite to enhance the TC adsorption capacity. Cycle regeneration and fixed bed column experiments revealed that the PEI@MMA-1 possessed the excellent stability and utility. Current PEI@MMA-1 cellulose composite exhibited a promising application for remediation of heavy metals and antibiotics coexistence wastewater.

Bio-based adsorption foam composed of MOF and polyethyleneimine-modified cellulose for selective anionic dye removal.

With the increase of sustainable development goal, the bio-based adsorption materials with high and selective dye removal are important for water treatment in the dyeing industry. In this paper, a bio-based adsorption foam composed of metal-organic frameworks (MOF) and polyethyleneimine (PEI)-modified cellulose was prepared by a three-step process, i.e., PEI modification of cellulose fibers (PC), MOF decoration of PEI-modified cellulose (MIL-53@PC), and in-situ foaming with polyurethane. PEI modification provides cellulose fiber with more active sites for both dye adsorption and MOF bonding. We found that MIL-53 crystals were tightly bonded on the surface of PC through hydrogen bonding. Because of the abundant adsorption sites (e.g., amines, iron oxide group), the MIL-53@PC demonstrated high adsorption capacity and selectivity for anionic dye (e.g., 936.5 mg/g for methyl orange) through electrostatic interaction and hydrogen bonding. Finally, MIL-53@PC particles were blended with a waterborne polyurethane prepolymer to prepare a three-dimensional hydrophilic foam (MIL-53@PC/PUF), which not only maintained high adsorption capacity and selectivity of MIL-53@PC and also improved its recyclability and reusability. The MIL-53@PC/PUF offers a promising solution for dye wastewater treatment.

Polyethylenimine grafted-chitosan based Gambogic acid copolymers for targeting cancer cells overexpressing transferrin receptors.

Recent advancements in gene delivery systems that specifically target a variety of cancer types have increased demand for tissue-specific gene therapy. The current study describes the synthesis of a copolymer (GPgWSC) composed of a polyethylenimine (PEI)-grafted water-soluble chitosan (WSC) and gambogic acid (GA). It was validated as a ligand capable of enabling targeted attachment to transferrin receptors in HCT116 cancer cell lines. GPgWSC demonstrated superior antitumor activity in vitro in HCT116 compared to LoVo or MCF-7 cell lines, facilitated by the apoptotic activity of psiRNA-hBCL2. Pre-incubation of transferrin significantly inhibited GFP expression in the GPgWSC polyplex, demonstrating that GA is an extremely effective transferrin receptor targeting molecule. Additionally, in the HCT116-bearing mouse model, the tumor mass of PBS-treated mice increased to 2270 mm2 after 22 days, but the injection of GPgWSC polyplex significantly reduced the mass-increasing rate as a mass size of 248 mm2.

PEG-PEI/siROCK2 inhibits Aß42-induced microglial inflammation via NLRP3/caspase 1 pathway.

OBJECTIVES: There is an urgent need to develop therapeutic strategies to improve the treatment outcome of Alzheimer's disease. The treatment strategy of gene therapy mediated by nanocarrier systems brings new hope for the treatment of Alzheimer's disease. ROCK2 is involved in various pathological processes of Alzheimer's disease and may be a potential target for the treatment of Alzheimer's disease. Our previous study indicated that PEG-PEI/siROCK2 [polyethyleneglycol-polyethyleneimine deliver ROCK2-siRNA, (PPSR)] prevented Aß42-induced neurotoxicity and showed a promising prospect for the treatment of Alzheimer's disease. However, whether PPSR has an effect on the microglial inflammation in Alzheimer's disease is still unclear. MATERIALS AND METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to detect the cytotoxicity of PEG-PEI and PPSR in primary microglial cells. Real-time PCR and western blotting were used to assess the expression of ROCK2 and nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase 1 pathway in primary microglial cells. ELISA assay was used to measure the effect of PPSR on attenuating the lipopolysaccharide (LPS) + Aß-induced increase in IL-1ß. RESULTS: PEG-PEI concentration less than 20 µg/ml and the N/P (molar ratio of PEG-PEI amino/siRNA phosphate) ratio of PPSR less than 50 showed no significant cytotoxicity in primary microglia cells. PPSR could effectively inhibit the expression of ROCK2 in primary microglial cells. A further study revealed that PPSR attenuates the LPS+Aß-induced increase in IL-1ß without affecting cell viability. In addition, we found that PPSR suppressed the Aß-induced NLRP3/caspase 1 pathway in primary microglial cells. CONCLUSION: PPSR inhibits Aß42-induced microglial inflammation via NLRP3/caspase 1 pathway.

Green synthesized nano-cellulose polyethylene imine-based biological membrane.

In hemodialysis process, membrane serves as a barrier between blood and the dialysate. The barrier when contacted by blood accompanied activation of coagulation, immunity, and cellular passageways. In the recent years, hemodialysis membrane's biocompatibility has become a issue which leads to reduce the performance during the separation process. In previous work, we developed and evaluated a cellulose-based membrane blended with polyaziridine or polyetyleneimine in formic acid for hydrophilicity, pure water flux, surface morphology, and permeation efficiency. Biocompatibility was accessed, by conducting cellular viability and cellular attachments tests. In this study, the membrane compared to a non-treated control, and cell viability revealed active and growing cell cultures after 14 days. During the cellular attachment experiment, cell cultures attached to the fabricated membrane simulated the formation of cell junctions, proving that the membrane is non-toxic and biocompatible. CA + PEI + FA membrane tested with a blood mimic fluid having density identical to renal patient's blood. The BSA concentration in the feed solution was the same as that in the blood of the renal patient. The results revealed that the CA + PEI + FA membrane was able to reject 99% bovine serum albumin (BSA) and 69.6% urea. Therefore, from biocompatibility and blood mimic fluid testing, it is confirmed that the CA + PEI + FA membrane is the finest implant for dialysis applications.

In Vivo Delivery of siRNAs Targeting EGFR and BRD4 Expression by Peptide-Modified Redox Responsive PEG-PEI Nanoparticles for the Treatment of Triple-Negative Breast Cancer.

The study aims to investigate the in vivo distribution, antitumor effect, and safety of cell membrane-penetrating peptide-modified disulfide bond copolymer nanoparticles loaded with small-interfering RNA (siRNA) targeting epidermal growth factor receptor (EGFR) and bromodomain-containing protein 4 (BRD4) in triple-negative breast cancer (TNBC). Polyethylene glycol disulfide bond-linked polyethylenimine (PEG-SS-PEI) was modified with peptides GALA and CREKA and used as vectors to prepare siRNA nanoparticles. The GALA- and CREKA-modified PEG-SS-PEI nanoparticles (GC-NPs) were prepared by mixing siEGFR and siBRD4 (1:1) with GALA-PEG-SS-PEI and CREKA-PEG-SS-PEI (1:1) in an aqueous solution at an N/P ratio of 30:1. Nanoparticles loaded with scrambled siRNA were prepared with the same method. The gene silencing effect on EGFR and BRD4 in vitro was evaluated by Western blotting analysis. TNBC xenograft models were established by subcutaneous injection of MDA-MB-231 cells into female nude mice. At 1, 3, 6, 12, and 24 h after administration of five formulations of Cy5-siRNA (133 µg/10 g) via the tail vein, the mice were observed and imaged for a biodistribution study using an in vivo imaging system. In the pharmacodynamics experiment, tumor-bearing mice were treated with respective siRNA preparations at a dose of 133 µg/10 g for 18 days, and the body weight and tumor size were recorded every other day. The protein expression levels of EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt, BRD4, and c-Myc were determined using Western blotting analysis. Hematological and serum biochemical parameters, organ indices, and HE staining results for the heart, liver, spleen, lung, and kidney were analyzed to evaluate the safety of the nanoparticles. GC-NPs loaded with siEGFR and siBRD4 significantly inhibited the expression of EGFR and BRD4 in vitro. The strongest fluorescence signals were observed in the GC-NP group, especially in tumors, indicating the excellent tumor-targeted delivery of GC-NPs we constructed. Tumor growth was significantly inhibited in the GC-NP-treated group, and the expression of EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt, BRD4, and c-Myc in the tumors decreased by 71%, 68%, 61%, 68%, 48%, 58%, 59%, and 74% compared to the control group, respectively. There was no significant change in hematological parameters, biochemical indices, or tissue morphology in GC-NP-treated mice. SiRNA cotargeting EGFR and BRD4 delivered by GALA- and CREKA-modified PEG-SS-PEI had favorable antitumor effects in vivo toward TNBC with tumor-targeting efficacy and good biocompatibility.

Polyethylenimine-Bisphosphonate-Cyclodextrin Ternary Conjugates: Supramolecular Systems for the Delivery of Antineoplastic Drugs.

Bisphosphonates (BPs) are bone-binding molecules that provide targeting capabilities to bone cancer cells when conjugated with drug-carrying polymers. This work reports the design, synthesis, and biological evaluation of polyethyleneimine-BP-cyclodextrin (PEI-BP-CD) ternary conjugates with supramolecular capabilities for the loading of antineoplastic drugs. A straightforward, modular, and versatile strategy based on the click aza-Michael addition reaction of vinyl sulfones (VSs) allows the grafting of BPs targeting ligands and ßCD carrier appendages to the PEI polymeric scaffold. The in vitro evaluation (cytotoxicity, cellular uptake, internalization routes, and subcellular distribution) for the ternary conjugates and their doxorubicin inclusion complexes in different bone-related cancer cell lines (MC3T3-E1 osteoblasts, MG-63 sarcoma cells, and MDA-MB-231 breast cancer cells) confirmed specificity, mitochondrial targeting, and overall capability to mediate a targeted drug transport to those cells. The in vivo evaluation using xenografts of MG-63 and MDA-MB-231 cells on mice also confirmed the targeting of the conjugates.

Enhanced Gene Delivery and CRISPR/Cas9 Homology-Directed Repair in Serum by Minimally Succinylated Polyethylenimine.

Gene therapy aims to treat patients by altering or controlling gene expression. The field of gene therapy has had increasing success in recent years primarily using viral-based approaches; however, there is still significant interest toward the use of polymeric materials due to their potential as flexible, low-cost scaffolds for gene delivery that do not suffer the mutagenesis and immunogenicity concerns of viral vectors. To address the challenges of efficiency and biocompatibility, a series of zwitterion-like polyethylenimine derivatives (zPEIs) were produced via the succinylation of 2-11.5% of polyethylenimine (PEI) amines. With increasing modification, zPEI polyplexes exhibited decreased serum-protein aggregation and dissociated more easily in the presence of a competitor polyanion when compared to unmodified PEI. Surprisingly, the gene delivery mediated in the presence of serum showed that succinylation of as few as 2% of PEI amines resulted in transgene expression 260- to 480-fold higher than that of unmodified PEI and 50- to 65-fold higher than that of commercial PEI-PEG2k in HEK293 and HeLa cells, respectively. Remarkably, the same zPEIs also produced 16-fold greater efficiency of CRISPR/Cas9 gene knock-in compared to unmodified PEI in the presence of serum. In addition, we show that 2% succinylation does not significantly decrease polymer/DNA binding ability or serum protein interaction to a significant extent, yet this small modification is still sufficient to provide a remarkable increase in transgene expression and gene knock-in in the presence of serum.

Enhancement of cytotoxicity and induction of apoptosis by cationic nano-liposome formulation of n-butylidenephthalide in breast cancer cells.

Breast cancer is the second most common malignancy in women. Current clinical therapy for breast cancer has many disadvantages, including metastasis, recurrence, and poor quality of life. Furthermore, it is necessary to find a new therapeutic drug for breast cancer patients to meet clinical demand. n-Butylidenephthalide (BP) is a natural and hydrophobic compound that can inhibit several tumors. However, BP is unstable in aqueous or protein-rich environments, which reduces the activity of BP. Therefore, we used an LPPC (Lipo-PEG-PEI complex) that can encapsulate both hydrophobic and hydrophilic compounds to improve the limitation of BP. The purpose of this study is to investigate the anti-tumor mechanisms of BP and BP/LPPC and further test the efficacy of BP encapsulated by LPPC on SK-BR-3 cells. BP inhibited breast cancer cell growth, and LPPC encapsulation (BP/LPPC complex) enhanced the cytotoxicity on breast cancer by stabilizing the BP activity and offering endocytic pathways. Additionally, BP and LPPC-encapsulated BP induced cell cycle arrest at the G0/G1 phase and might trigger both extrinsic as well as intrinsic cell apoptosis pathway, resulting in cell death. Moreover, the BP/LPPC complex had a synergistic effect with doxorubicin of enhancing the inhibitory effect on breast cancer cells. Consequently, LPPC-encapsulated BP could improve the anti-cancer effects on breast cancer in vitro. In conclusion, BP exhibited an anti-cancer effect on breast cancer cells, and LPPC encapsulation efficiently improved the cytotoxicity of BP via an acceleration of entrapment efficiency to induce cell cycle block and apoptosis. Furthermore, BP/LPPC exhibited a synergistic effect in combination with doxorubicin.

Rapid Antibacterial Effects of Silk Fabric Constructed through Enzymatic Grafting of Modified PEI and AgNP Deposition.

Enzymatic antibacterial finishing is an eco-friendly alternative to develop functional silk-based materials. However, the low accessibility of tyrosine residues distributed in fibroin chains restricts the laccase-mediated functionalization of silk fibers (SF). To address this issue, a highly reactive p-hydroxyphenylacetic acid-modified polyethyleneimine (mPEI) was enzymatically grafted onto fibroin using laccase, aiming at constructing an antibacterial matrix of mPEI on the fiber surface. Subsequently, in situ deposition of silver nanoparticles (i.e., AgNPs) into the newly built mPEI network was performed to form a rapid antibacterial layer. The results indicated that laccase efficiently catalyzes the mPEI coupling, the zeta potential of SF-g-mPEI increases from -32 to 21.70 mV, and the silver content reaches 1.81% after AgNP embedment. Based on the combined two-step treatments, the obtained silk fabric exhibited excellent antibacterial abilities against two bacteria, including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The antibacterial rates of both bacteria reached 99.9% within 30 min of contact, remaining over 99.9% within 18 h of contact even after washing 10 times. The present work provides an enzyme-mediated method for construction of silk fabric with durable and rapid antibacterial activity.

Fabrication of polyethylenimine functionalized magnetic cellulose nanofibers for the sorption of Ni(II), Cu(II) and Cd(II) in single-component and multi-component systems.

Novel polyethyleneimine functionalized cellulose nanofiber magnetic composites (PEI-CNFs@Fe3O4) were prepared using banana peels as the raw materials for the sorption of Ni(II), Cu(II) and Cd(II) in single-component and multi-component systems. The batch experiments, spectral analyses and model fittings were used to reveal the sorption properties. The sorption of Ni(II), Cu(II) and Cd(II) on PEI-CNFs@Fe3O4 all conformed to the Langmuir isotherm and pseudo-second-order kinetic models. And the maximum sorption capacities of PEI-CNFs@Fe3O4 towards Ni(II), Cu(II) and Cd(II) were 134.38, 93.71 and 173.56 mg g-1, respectively. The main sorption mechanism of Ni(II), Cu(II) and Cd(II) on PEI-CNFs@Fe3O4 is the strong surface complexation of the amino, carboxyl and hydroxyl groups with Ni(II), Cu(II) and Cd(II) ions. Especially, the introduction of PEI contributed to the improvement in the sorption capacities of PEI-CNFs@Fe3O4 towards the heavy metals. Besides, the size of the ionic radius and the strength of the surface complexing ability with PEI-CNFs@Fe3O4 are the reasons for the difference in the sorption capacities of Ni(II), Cu(II) and Cd(II) (Cd(II) > Ni(II) > Cu(II)). In conclusion, PEI-CNFs@Fe3O4 has shown the advantages of low cost, simple preparation, easy magnetic separation, environmental friendliness and high sorption capacity, thus having a broad application prospect in the treatment of multi-heavy metals polluted water.

Tumor-Penetrable Nitric Oxide-Releasing Nanoparticles Potentiate Local Antimelanoma Therapy.

Although nitric oxide (NO) has been emerging as a novel local anticancer agent because of its potent cytotoxic effects and lack of off-target side effects, its clinical applications remain a challenge because of the short effective diffusion distance of NO that limits its anticancer activity. In this study, we synthesized albumin-coated poly(lactic-co-glycolic acid) (PLGA)-conjugated linear polyethylenimine diazeniumdiolate (LP/NO) nanoparticles (Alb-PLP/NO NPs) that possess tumor-penetrating and NO-releasing properties for an effective local treatment of melanoma. Sufficient NO-loading and prolonged NO-releasing characteristics of Alb-PLP/NO NPs were acquired through PLGA-conjugated LP/NO copolymer (PLP/NO) synthesis, followed by nanoparticle fabrication. In addition, tumor penetration ability was rendered by the electrostatic adsorption of the albumin on the surface of the nanoparticles. The Alb-PLP/NO NPs showed enhanced intracellular NO delivery efficiency and cytotoxicity to B16F10 murine melanoma cells. In B16F10-tumor-bearing mice, the Alb-PLP/NO NPs showed improved extracellular matrix penetration and spatial distribution in the tumor tissue after intratumoral injection, resulting in enhanced antitumor activity. Taken together, the results suggest that Alb-PLP/NO NPs represent a promising new modality for the local treatment of melanoma.

PEG-PEI-modified gated N-doped mesoporous carbon nanospheres for pH/NIR light-triggered drug release and cancer phototherapy.

A novel hybrid drug carrier has been designed, taking N-doped mesoporous carbon (NMCS) as the core and PEG-PEI as the outer shell. NMCS was functionalized with a photocleavable nitrobenzyl-based linker following a click reaction. Gemcitabine was loaded into NMCS prior to the functionalization via π-π stacking interactions. NIR and the pH-responsive behavior of NMCS-linker-PEG-PEI bestow the multifunctional drug carrier with the controlled release of gemcitabine triggered by dual stimuli. The NMCS core upconverts NIR light to UV, which is absorbed by a photosensitive molecular gate and results in its cleavage and drug release. Further, NMCS converts NIR to heat, which deforms the outside polymer shell, thus triggering the drug release process. The release can be promptly arrested if the NIR source is switched off. A promising gemcitabine release of 75% has been achieved within 24 h under the dual stimuli of pH and temperature. NMCS-linker-PEG-PEI produced reactive oxygen species (ROS), which were verified in FaDu cells using flow cytometry. In vitro experiments showed that the NMCS-linker-PEG-PEI-GEM hybrid particle can induce synergistic therapeutic effects in FADU cells when exposed to the NIR light.

Rapid and high selective removal of Hg(II) ions using tannic acid cross-linking cellulose/polyethyleneimine functionalized magnetic composite.

In this study, a new tannic acid cross-linking cellulose/polyethyleneimine functionalized magnetic composite (MCP) as a biomass adsorbent of Hg(II) ions was prepared. The morphology and structure of MCP were characterized with FT-IR, TG, XRD, SEM and TEM. The effect of the different factors such as pH, contact time, initial Hg(II) ion concentration, and adsorption temperature on the adsorption behavior was investigated. The results showed that MCP exhibited an excellent selectivity and reutilization, fast removal rate, and very high adsorption capacity. The corresponding adsorption capacity and removal rate of could reach 99.00% and 247.51 mg/g when the pH value, adsorption time, Hg(II) ion concentration were 5, 180 min and 100 mg/L at 293 K. The kinetics followed the pseudo-second-order, which indicated that the adsorption behavior of MCP for Hg(II) ion belonged to the chemical adsorption process and external diffusion. The thermodynamic study showed that the adsorption process was a spontaneous and exothermic process. After the fifth adsorption-desorption experiment, it still had better adsorption performance and reutilization. All in all, MCP with highly stable and efficient, as well as excellent reusability will be a candidate for industry-level applications from wastewater with Hg(II) ions.

Dopamine-polyethyleneimine co-deposition cellulose filter paper for α-Glucosidase immobilization and enzyme inhibitor screening.

In this work, cellulose filter paper (CFP), which is inexpensive and commercially available, was used as the carrier, and the immobilized α-glucosidase was obtained by two steps: firstly, the surface of CFP was modified by polydopamine/polyethyleneimine (PDA/PEI) co-deposition method to obtain CFP-PDA/PEI with a uniform coating of rich positive charge; subsequently, α-glucosidase was immobilized on the CFP-PDA/PEI by electrostatic adsorption. The free enzyme and immobilized enzyme have the same optimal temperature (70℃) and pH (8.0), and their Km is similar, which is 2.2 and 2.8, respectively. These results show that the immobilization process does not change the properties of the enzyme greatly. The immobilized enzyme still maintains 75.6% of its initial activity after 10 repeated uses, showing good reusability. The excellent repeatability (RSD = 2.2%, n = 5) and the verification of competitive inhibitor (acarbose) illustrates the reliability of the immobilized enzymes for enzyme inhibitor screening. Finally, combined with CE, a screening method based immobilized α-glucosidase was proposed and applied to screen the α-glucosidase inhibitory from 10 kinds of Traditional Chinese medicines (TCMs) in vitro. The results indicated that the method was a very effective tool for screening potential α-glucosidase inhibitors from TCMs.

Hierarchical Self-assembly of Discrete Metal-Organic Cages into Supramolecular Nanoparticles for Intracellular Protein Delivery.

Hierarchical self-assembly (HAS) is a powerful approach to create supramolecular nanostructures for biomedical applications. This potency, however, is generally challenged by the difficulty of controlling the HAS of biomacromolecules and the functionality of resulted HAS nanostructures. Herein, we report a modular approach for controlling the HAS of discrete metal-organic cages (MOC) into supramolecular nanoparticles, and its potential for intracellular protein delivery and cell-fate specification. The hierarchical coordination-driven self-assembly of adamantane-functionalized M12 L24 MOC (Ada-MOC) and the host-guest interaction of Ada-MOC with ß-cyclodextrin-conjugated polyethylenimine (PEI-ßCD) afford supramolecular nanoparticles in a controllable manner. HAS maintains high efficiency and orthogonality in the presence of protein, enabling the encapsulation of protein into the nanoparticles for intracellular protein delivery for therapeutic application and CRISPR/Cas9 genome editing.

Characterization of positively charged polyplexes by tunable resistive pulse sensing.

With the approval of the first siRNA-based drugs, non-viral siRNA delivery has gained special interest in industry and academia in the last two years. For non-viral delivery, positively charged lipid and polymer formulations play a central role in research and development. However, nanoparticle size characterization, particularly of polydisperse formulations, can be very challenging. Tunable resistive pulse sensing for particle by particle measurements of size, polydispersity, zeta potential and a direct concentration promises better assessment of nanoparticle formulations. However, the current application is not optimized for positively charged particles. A supplier-provided coating solution for difficult-to-measure samples does not allow for successful measurements of positively charged nanoparticles. This article describes a new coating solution based on choline-chloride. Coating is verified by current-voltage (I-V) recordings and ultimately tested on a positively charged nanoparticle formulation comprising of siRNA and PEG-PCL-PEI polymer. This coating allows successful size, polydispersity index (PDI) and concentration measurement by tunable resistive pulse sensing of positively charged PEI-based polyplexes. This article provides the foundation for further characterization of polyplexes as well as other positively charged nanoparticle formulations based on particle by particle measurements.

Co-delivery of EGFR and BRD4 siRNA by cell-penetrating peptides-modified redox-responsive complex in triple negative breast cancer cells.

AIMS: Triple negative breast cancer (TNBC) has drawn more and more attention due to its high mitotic indices, high metastatic rate and poor prognosis. Gene therapy, especially RNA interference (RNAi), has become a promising targeted therapy. However, improvement of transfection efficiency and discovery of target genes are major problems for the delivery of small interfering RNAs (siRNA). MATERIALS AND METHODS: In the present study, we developed GALA- and CREKA-modified PEG-SS-PEI to deliver siRNAs targeting on EGFR and BRD4 for TNBC therapy. The PEG-SS-PEI/siRNA complexes were prepared by electrostatic interaction and characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The release characteristic, stability, cellular uptake and intracellular localization of the complexes were also studied. The effect of the complexes on cell viability was measured in MDA-MB-231 and HUVEC cells. The in vitro anti-tumor activities of the complexes were analyzed by Transwell invasion assay and wound healing assay. The gene silencing effect was evaluated by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot. KEY FINDINGS: The results revealed that the GALA- and CREKA-modified PEG-SS-PEI/siRNA complexes showed excellent transfection efficiency with redox-sensitive release profile and good biological compatibility. The complexes protected siRNA from the degradation of RNA enzymes. The complexes significantly inhibited the proliferation, invasion and migration of MDA-MB-231 cells via the synergistic inhibition of EGFR/PI3K/Akt and BRD4/c-Myc pathways. SIGNIFICANCE: Taken together, co-delivery of siEGFR and siBRD4 by GALA-PEG-SS-PEI and CREKA-PEG-SS-PEI may provide a more effective strategy for the treatment of TNBC.

Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid to treat bacterial endophthalmitis: Development, characterization, and ocular biocompatibility.

Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid (VCM-DMPEI nanoparticles/HA) were synthesized as an adjuvant for the treatment of bacterial endophthalmitis. The nanoparticles were formulated by experimental statistical design, thoroughly characterized, and evaluated in terms of bactericidal activity and both in vitro and in vivo ocular biocompatibility. The VCM-DMPEI nanoparticles/HA were 154 ± 3 nm in diameter with a 0.197 ± 0.020 polydispersity index; had a + 26.4 ± 3.3 mV zeta potential; exhibited a 93% VCM encapsulation efficiency; and released 58% of the encapsulated VCM over 96 h. VCM and DMPEI exhibited a synergistic bactericidal effect. The VCM-DMPEI nanoparticles/HA were neither toxic to ARPE-19 cells nor irritating to the chorioallantoic membrane. Moreover, the VCM-DMPEI nanoparticles/HA did not induce modifications in retinal functions, as determined by electroretinography, and in the morphology of the ocular tissues. In conclusion, the VCM-DMPEI nanoparticles/HA may be a useful therapeutic adjuvant to treat bacterial endophthalmitis.