US/PA/MR multimodal imaging-guided multifunctional genetically engineered bio-targeted synergistic agent for tumor therapy.

Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy.

Micellar Nanogels from Alginate-Based Diblock Copolysaccharides.

Alginates are marine polysaccharides known for their ability to selectively bind calcium ions and form hydrogels. They are widely used in biomedical applications but are challenging to produce as nanogels. Here we introduce a self-assembly route to create stable alginate-based nanogels under near-equilibrium conditions. Guluronate (G) blocks, which interact with divalent cations such as Ca2+, Ba2+, and Sr2+, were extracted from alginates and covalently linked through their reducing end to the reducing end of dextran (Dex) chains, forming linear block copolymers that self-assemble into micellar nanogels with a core-corona structure in the presence of these ions. Real-time dynamic light scattering (DLS) and small-angle neutron scattering (SANS) were used to study the self-assembly mechanism of the copolymer during dialysis against divalent ions. For the G12-b-Dex51 copolymer, we achieved spherical micelles with an 8 nm radius and an aggregation number of around 20. Although the type of divalent cation affected micelle stability, it did not influence their size. Micellar nanogels are dynamic structures, capable of ion exchange, and can disassemble with chelating agents like ethylenediamine tetraacetic acid (EDTA).

Aptamer-guided graphene oxide quantum dots for targeted suicide gene therapy in an organoid model of luminal breast cancer.

Breast cancer is one of the most common cancers in women. One of the best therapeutic methods against breast cancer is gene therapy, while having an appropriate gene carrier is the biggest challenge of gene therapy. Hence, developing carriers with low cytotoxicity and high gene transfection efficiency, and preferentially with the selective function of gene delivery is a critical demand for this method. In the present study, we introduce a novel targeted carrier to deliver the inducible caspase-9 suicide gene (pLVSIN-iC9) into breast cancer cells. The carrier is composed of graphene oxide quantum dots decorated with polyethyleneimine, and S2.2; an aptamer with high affinity to MUC1 (GOQD-PEI/S2.2). Due to the overexpression of MUC1 in breast cancer cells, the designed GOQD-PEI/S2.2/pLVSIN-iC9 can selectively target cancer cells. Moreover, to better mimic solid tumor conditions, and to evaluate the selective effect of the GOQD-PEI/S2.2/pLVSIN-iC9, an organoid model derived from human dermal fibroblasts (HDF) and MCF-7 cells (coculture organoid) was generated and characterized. The results demonstrate that the coculture organoid model adapts the tissue structure of luminal breast cancer, as well. Therefore, the organoids were subjected to treatment with targeted gene therapy using GOQD-PEI/S2.2/pLVSIN-iC9. Our evidence supports the targeted killing effect of iC9 on the breast cancer cells of the organoids and suggests the good potential of the newly introduced carriers in targeted gene delivery.

Dihydroxyphenylalanine-conjugated high molecular weight polyethylenimine for targeted delivery of Plasmid.

High molecular weight polyethylenimine (HMW PEI; branched 25 kDa PEI) has been widely investigated for gene delivery due to its high transfection efficiency. However, the toxicity and lack of targeting to specific cells have limited its clinical application. In the present investigation, L-3, 4-dihydroxyphenylalanine (L-DOPA) was conjugated on HMW PEI in order to target L-type amino acid transporter 1 (LAT-1) and modulate positive charge density on the surface of polymer/plasmid complexes (polyplexes). The results of biophysical characterization revealed that the PEI conjugates are able to form nanoparticles ≤ 180 nm with the zeta potential ranging from + 9.5-12.4 mV. These polyplexes could condense plasmid DNA and protect it against nuclease digestion at the carrier to plasmid ratios higher than 4. L-DOPA conjugated PEI derivatives were complexed with a plasmid encoding human interleukin-12 (hIL-12). Targeted polyplexes showed up to 2.5 fold higher transfection efficiency in 4T1 murine mammary cancer cell line, which expresses LAT-1, than 25 kDa PEI polyplexes prepared in the same manner. The cytotoxicity of these polyplexes was also substantially lower than the unmodified parent HMW PEI. These results support the use of L-3, 4-dihydroxyphenylalanine derivatives of PEI in any attempt to develop a LAT-1 targeted gene carrier.

Simplified Synthesis of Poly(ethyleneimine)-Modified Silica Particles and Their Application in Oligosaccharide Isolation Methods.

There are great challenges in the field of natural product isolation and purification and in the pharmacological study of oligosaccharide monomers. And these isolation and purification processes are still universal problems in the study of natural products (NPs), traditional Chinese medicine (TCM), omics, etc. The same polymer-modified materials designed for the special separation of oligosaccharides, named Sil-epoxy-PEI and Sil-chloropropyl-PEI, were synthesized via two different methods and characterized by scanning electron microscopy combined with energy spectrum analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential as well as surface area analysis, etc. Several nucleotide/nucleoside molecules with different polarities and selectivities were successfully isolated in our laboratory using stainless-steel columns filled with the synthesized material. In addition, the separation of saccharide probes and oligosaccharides mixtures in water extracts of Morinda officinalis were compared in HILIC mode. The results showed that the resolution of separations for the representative analytes of the Sil-epoxy-PEI column was higher than for the Sil-chloropropyl-PEI column, and the developed stationary phase exhibited improved performance compared to hydrothermal carbon, amide columns and other HILIC materials previously reported.

Glycogen nanoparticles for efficient mRNA transduction to T lymphocytes.

T lymphocyte therapies demonstrate significant promise in the treatment of cancer and infectious diseases. An efficient gene delivery system is essential for the safe and reliable introduction of exogenous genes, especially mRNA, into cells to achieve therapeutic purposes. Commercial transfection reagents are suitable for the transduction of plasmids to adherent cells, whereas they are ineffective for suspension cells such as T lymphocytes and for unstable mRNA. Moreover, the cytotoxicity of transfection reagents themselves constitutes an impediment to their application. The challenge of mRNA transduction to T lymphocytes with high efficiency is notably formidable. An innovative transfection strategy is urgently needed. In this study, we synthesized aminated glycogen (AGly) nanoparticles as gene vectors, encapsulating mRNA to facilitate the efficient transfection of T lymphocytes. Compared to commercial transfection reagent polyethylenimine (PEI), the AGly demonstrated favorable biocompatibility. The positive charge provided AGly with pH buffering ability and mRNA-binding capacity. AGly formed stable nanoparticles with mRNA, which were readily internalized by suspension cells and enhanced the cellular uptake of mRNA. In the T lymphocyte model cell lines (Jurkat cells and HuT 78 cells), AGly demonstrated superior transfection efficiency than that of PEI. Consequently, AGly can emerge as a viable mRNA vector for the efficient transfection of T lymphocytes whilst circumventing the issue of cytotoxicity. The AGly designed in this study provides a novel concept for the exploitation of transfection reagents and proposes a promising methodology for the proficient transfection of T lymphocytes which may significantly contribute to the treatment of cancer and other complex diseases.

Immunogenicity of Brucella Trivalent Immunogen-Containing Polyethyleneimine Nanostructure Targeted with LPS in a Mouse Model.

Brucella is a facultative intracellular gram-negative coccobacillus. It is nonsporulating and reproduced in macrophage phagosomes. The use of nanostructures as drug and vaccine carriers has recently received attention due to their ability to control the release profile and protect the drug molecules. This study presents a suitable nano-polyethyleneimine formulation to be used as an immunoadjuvant and LPS along with trivalent candidate antigens of TF, BP26, and omp31 to selectively stimulate the immune response. After designing and evaluating the immunogenic structure by databases and bioinformatics software, recombinant protein cloning and gene expression were performed in Escherichia coli BL21 bacteria. This protein was extracted from the cultured cells, purified by Ni-NTA column. After placing the antigen inside the polyethyleneimine nanostructure, various properties of the nanoparticles, including their size, zeta potential, and retention rate for injection and inhalation of mice, diffusion efficacy, and antigen binding evaluation were evaluated. Mice were treated with different groups of antigens and nanoparticles on days 0, 10, 24, and 38. Two weeks after the last injection, the level of cytokines were investigated in spleen cells, including IFN-γ, IL-4, and IL-12. The serum concentration of IgG2a and IgG1 antibodies were also assessed. The response was consistent with significant production of IgG1, IgG2a, IFN-γ21, IL-12, and IL-4 compared to the controls (P < 0.05). Compared to the positive and negative control groups, recombinant protein and nanoparticles showed a good response in subsequent injections with live bacterial strains. The present study also revealed the potential of the developed recombinant protein as a candidate in the design and manufacture of subunit vaccines against Brucella species. This protein stimulates cellular and humoral immune responses compared to the positive control groups. These findings can be useful in the prevention and control of brucellosis and pave the way for further research by researchers around the world.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The ß-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The ß-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. ß-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of ß-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Cationic Amphiphilic Comb-Shaped Polymer Emulsifier for Fabricating Avermectin Nanoemulsion with Exceptional Leaf Behaviors and Multidimensional Controlled Release.

The development of intelligent multifunctional nanopesticides featuring enhanced foliage affinity and hierarchical target release is increasingly pivotal in modern agriculture. In this study, a novel cationic amphiphilic comb-shaped polymer, termed PEI-TA, was prepared via a one-step Michael addition between low-molecular-weight biodegradable polyethylenimine (PEI) and tetradecyl acrylate (TA), followed by neutralization with acetic acid. Using the emulsifier PEI-TA, a positively charged avermectin (AVM) nanoemulsion was prepared via a phase inversion emulsification process. Under optimal formulation, the obtained AVM nanoemulsion (defined as AVM@PEI-TA) demonstrated exceptional properties, including small size (as low as 67.6 nm), high encapsulation efficiency (up to 87.96%), and high stability toward shearing, storage, dilution, and UV irradiation. The emulsifier endowed AVM@PEI-TA with a pronounced thixotropy, so that the droplets exhibited no splash and bounce when they were sprayed on the cabbage leaf. Owing to the electrostatic attraction between the emulsifier and the leaf, AVM@PEI-TA showed improved leaf adhesion, better deposition, and higher washing resistance in contrast to both its negatively charged counterpart and AVM emulsifiable concentrate (AVM-EC). Compared to the large-sized particles, the small-sized particles of the AVM nanoemulsion more effectively traveled long distances through the vascular system of veins after entering the leaf apoplast. Moreover, the nanoparticles lost stability when exposed to multidimensional stimuli, including pH, temperature, esterase, and ursolic acid individually or simultaneously, thereby promoting the release of AVM. The release mechanisms were discussed for understanding the important role of the emulsifier in nanopesticides.

Bioresponsive Nanoparticles Boost Starvation Therapy and Prevent Premetastatic Niche Formation for Pulmonary Metastasis Treatment.

In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

Under Water Superelastic Porous Nanofibrous Sponge for Efficient RNA Separation and Purification.

Developing monolithic materials for chromatography columns with a novel interconnected porous structure is vital for the enhancement of the separation efficiency of RNA purification processes. Herein, a porous nanofibrous sponge (PNFS) is constructed by freeze molding and freeze-drying a nanofiber dispersion with ethylene vinyl alcohol copolymer nanofibers as the skeleton, chitosan (CS) and polyethylenimine (PEI) as the binders, and glutaraldehyde (GA) as the crosslinking agent. The results show that when the CS content of the dispersion is 1.5 wt %, PNFS demonstrates a high static adsorption capacity of 406.5 mg/g (30.7 mg/m2) and a dynamic adsorption capacity of 382.6 mg/g (28.9 mg/m2) at a flow rate of 1 mm/min. Moreover, PNFS shows a high specific adsorption performance toward RNA in the presence of bovine serum albumin, lecithin, or DNA by adjusting the solution pH value and the method of gradient elution. Besides, PNFS presents exceptional performance in the rapid separation of RNA from HT22 cells without degradation. This result can be attributed to optimized morphology, pore structure, and comprehensive performance of PNFS, benefiting from the synergistic effect of the highly oriented porous structure and CS-PEI interaction derived from the high-density adsorption ligands on the channel walls of PNFS. This work provided an efficient strategy to handle the permeability/adsorptivity trade-off for ion-exchange chromatographic materials.

A tough, strong, and fast-curing phenolic resin enabled by dopamine-grafted chitosan and polyethyleneimine-functionalized graphene.

Phenolic resins are widely used for outdoor and structural wood-based panels; however, they are challenged by high curing temperatures, low curing rates, and high brittleness. Inspired by lobster epidermis hardening, a tough, strong, and fast-curing phenolic resin (named DCS/PG/PF) was proposed herein. In this approach, dopamine-grafted chitosan (DCS) and polyethyleneimine-functionalized graphene (PEI@G) were incorporated into neat phenol formaldehyde (PF) resin. The gel time and maximum curing temperature of DCS/PG/PF resin were considerably reduced from 445 s and 147.8 °C for the neat PF resin to 317 s and 127.8 °C, respectively. This was attributed to the oxidative crosslinking of catechol moieties in DCS and amino groups in PEI@G within the naturally alkaline environment of phenolic resins in addition to the high reactivity between catechol moieties and PF chains as well as between amino and PF chains. The prepared resin demonstrated a dry bonding strength of 2.56 MPa, wet bonding strength of 1.81 MPa, and debonding work of 0.714 J, exhibiting a considerable increase of 16.9 %, 52.1 %, and 95.1 %, respectively, compared with those of the PF resin. These improvements were attributed to the dense organic-inorganic hybrid crosslinking network formed in the DCS/PG/PF. Furthermore, the DCS/PG/PF resin exhibited enhanced thermal stability.

A splice-switch oligonucleotide loaded self-cleavable DNA nanogel.

A self-cleavable DNA nanogel loaded with splice-switch oligonucleotide (SSO) has been developed. Under acidic conditions (pH 5.0), cleavage of the acid-labile chemical linker and generation of the i-motif structure led to the disintegration of the DNA nanogel and efficient release of SSO in its unaltered native state.

A tough Janus poly(vinyl alcohol)-based hydrogel for wound closure and anti postoperative adhesion.

Traditional adhesive hydrogels perform well in tissue adhesion but they fail to prevent postoperative tissue adhesion. To address this challenge, a biodegradable Janus adhesive hydrogel (J-AH) was designed and fabricated by the assembly of three different functional layers including anti-adhesive layer, reinforceable layer, and wet tissue adhesive layer. Each layer of J-AH serves a specific function: the top zwitterionic polymeric anti-adhesive layer shows superior resistance to cell/protein and tissue adhesion; the middle poly(vinyl alcohol)/tannic acid reinforceable matrix layer endows the hydrogel with good mechanical toughness of ∼2.700 MJ/m3; the bottom poly(acrylic acid)/polyethyleneimine adhesive layer imparts tough adhesion (∼382.93 J/m2 of interfacial toughness) to wet tissues. In the rat liver and femoral injury models, J-AH could firmly adhere to the bleeding tissues to seal the wounds and exhibit impressive hemostatic efficiency. Moreover, in the in vivo adhesion/anti-adhesion assay of J-AH between the defected cecum and peritoneal walls, the top anti-adhesive layer can effectively inhibit undesired postoperative abdominal adhesion and inflammatory reaction. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels with multi-functions including tissue adhesion, anti-postoperative adhesion and biodegradation. STATEMENT OF SIGNIFICANCE: Despite many adhesive hydrogels with tough tissue adhesion capability have been reported, their proclivity for undesired postoperative adhesion remains a serious problem. The postoperative adhesion may lead to major complications and even endanger the lives of patients. The injectable hydrogels can cover the irregular wound and suppress the formation of postoperative adhesion. However, due to the lack of adhesive properties with tissue, it is difficult for the hydrogels to maintain on the wound surface, resulting in poor anti-postoperative adhesion effect. Herein, we design a Janus adhesive hydrogel (J-AH). J-AH integrates together robust wet tissue adhesion and anti-postoperative adhesion. Therefore, this research may present a new strategy for the design of advanced bio-absorbable Janus adhesive hydrogels.

Natural Binary Herbal Small Molecules Self-Assembled Nanogel for Synergistic Inhibition of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is one of the most significant pathogenic infections in childhood, associated with high morbidity and mortality rates. Currently, there is no effective and safe drug or vaccine available for RSV. Glycyrrhizic acid (GA), an active compound derived from the natural herb licorice, has been reported to provide protection against influenza and coronaviruses, exhibiting notable antiviral and anti-inflammatory properties. Ephedrine (EPH) is a commonly prescribed medication for the treatment of cough and asthma, and it also demonstrates certain antiviral effects. In this study, EPH and GA were combined to form an efficient nanomaterial (EPH-GA nanogel). The self-assembly of this nanogel is driven by hydrogen bonding and hydrophobic interactions, allowing it to serve as an antiviral nanomedicine without the need for a dual-component carrier, achieving a 100% drug loading efficiency. Oral administration of the EPH-GA nanogel significantly reduced viral load in the lungs of mice and improved lung lesions and tissue infiltration caused by RSV. Notably, we discovered that the assembled drug may create a "physical barrier" that prevents RSV from adsorbing to host cells, while free GA and EPH may compete with RSV for protein binding sites, thereby enhancing cellular uptake of EPH. Consequently, this prevents RSV infection and proliferation within host cells. Furthermore, the EC50 values changed from 310.83 µM for EPH and 262.88 µM for GA to 68.25 µM for the EPH-GA combination, with a combination index of 0.458. In addition, the in vivo biopharmaceutic process of GA and EPH was investigated, revealing that the oral administration of EPH-GA significantly increased the bioavailability of EPH while maintaining its plasma concentration at a relatively stable level. This enhancement may contribute to a synergistic antiviral effect when combined with GA. Furthermore, the in vivo process of EPH-GA demonstrates the advantage of delivering the drug to the lesion at elevated levels, thereby facilitating its antiviral mechanism at the cellular level. In this study, we identified an effective nanomedicine, EPH-GA nanogel, which can inhibit the proliferation of RSV and mitigate lung lesions resulting from viral infection by influencing the biopharmaceutical process in vivo. This research not only offers a novel strategy for the nanomedicine treatment of RSV but also elucidates, to some extent, the compatibility mechanisms of the multicomponents of traditional Chinese medicine.

Construction of intelligent response gene vector based on MOF/Fe3O4/AuNRs for tumor-targeted gene delivery.

Metal-organic frameworks (MOFs) have the potential to efficiently carry cargo due to their excellent porosity and high surface area. Nevertheless, conventional MOFs and their derivatives exhibit low efficiency in transporting nucleic acids and other small molecules, as well as having poor colloidal stability. In this study, a ZIF-90 loaded with iron oxide nanoparticles and Au nanorods was prepared, and then surface-functionalized with polyethyleneimine (PEI) to create a multifunctional nanocomposite (AFZP25k) with pH, photothermal, and magnetic responsiveness. AFZP25k can condense plasmid DNA to form AFZP25k/DNA complexes, with a maximum binding efficiency of 92.85 %. DNA release assay showed significant light and pH responsiveness, with over 80 % cumulative release after 6 h of incubation. When an external magnetic field is applied, the cellular uptake efficiency in HeLa cells reached 81.51 %, with low cytotoxicity and specific distribution. In vitro transfection experiments demonstrated a gene transfection efficiency of 44.77 % in HeLa cells. Following near-infrared irradiation, the uptake efficiency and transfection efficiency of AFZP25k in HeLa cells increased by 21.3 % and 13.59 % respectively. The findings indicate the potential of AFZP25k as an efficient and targeted gene delivery vector in cancer gene therapy.

A Photothermal Polymeric Platform for Efficient and Safe Gene Transfection: When Polyethylenimine Collaborates with Indocyanine Green.

Gene transfection, defined by the delivery of nucleic acids into cellular compartments, stands as a crucial procedure in gene therapy. While branched polyethylenimine (PEI) is widely regarded as the "gold standard" for nonviral vectors, its cationic nature presents several issues, including nonspecific protein adsorption and notable cytotoxicity. Additionally, it often fails to achieve high transfection efficiency, particularly with hard-to-transfect cell types. To overcome these challenges associated with PEI as a vector for plasmid DNA (pDNA), the photothermal agent indocyanine green (ICG) is integrated with PEI and pDNA to form the PEI/ICG/pDNA (PI/pDNA) complex for more efficient and safer gene transfection. The negatively charged ICG serves a dual purpose: neutralizing PEI's excessive positive charges to reduce cytotoxicity and, under near-infrared irradiation, inducing local heating that enhances cell membrane permeability, thus facilitating the uptake of PI/pDNA complexes to boost transfection efficiency. Using pDNA encoding vascular endothelial growth factor as a model, our system shows enhanced transfection efficiency in vitro for hard-to-transfect endothelial cells, leading to improved cell proliferation and migration. Furthermore, in vivo studies reveal the therapeutic potential of this system in accelerating the healing of infected wounds by promoting angiogenesis and reducing inflammation. This approach offers a straightforward and effective method for gene transfection, showing potentials for tissue engineering and cell-based therapies.

Immobilization of aldo-keto reductase on dopamine/polyethyleneimine functionalized magnetic cellulose nanocrystals to enhance the detoxification of patulin in fresh pear juice.

Patulin (PAT) is a highly toxic mycotoxin, which can contaminate fruits and their products and cause harm to human health. Cellulose nanocrystals (CNCs) were functionalized by magnetite nanoparticles, dopamine (DA) and polyethyleneimine (PEI) to form a multifunctional nanocarrier (DA/PEI@Fe3O4/CNCs) for immobilizing aldo-keto reductase (MgAKR) to degrade PAT. The MgAKR-DA/PEI@Fe3O4/CNCs were reusable and environmentally friendly due to its surface area, high magnetization value, and oxygen/amine function. The immobilization method significantly improved reusability, resistance to proteolysis, temperature stability and storage stability of MgAKR-DA/PEI@Fe3O4/CNCs. With NADPH as a coenzyme, the detoxification rate of MgAKR-DA/PEI@Fe3O4/CNCs on PAT reached 100 % in phosphate buffer and 98 % in fresh pear juice. The quality of fresh pear juice was unaffected by MgAKR-DA/PEI@Fe3O4/CNCs and could be quickly separated by magnet after detoxification, which was convenient for recycling. It has broad application prospects in the control of PAT contamination in beverage products containing fruit and vegetable ingredients.

A highly sensitive electrochemical immunosensor based on rGO-PEI-Ag nanocomposites for the detection of tilmicosin.

A label-free electrochemical immunosensor was developed to rapidly detect tilmicosin (TMC) residues in pork and milk. The immunosensor was constructed by immobilizing a high-affinity monoclonal antibody against TMC on an rGO-PEI-Ag nanocomposite-modified electrode. The rGO-PEI-Ag nanocomposites were prepared by mixing polyethyleneimine (PEI) modified reduced graphene oxide (rGO) with AgNO3 solution. The prepared rGO-PEI-Ag nanocomposites showed good redox activity and conductivity, as characterized by ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), and X-ray diffraction (XRD). During the preparation process, staphylococcal protein A (SPA) was added to targetedly bind the Fc segment of the monoclonal antibody. The immunosensor showed a low detection limit (LOD) of 0.0013 ng/mL, a linear range of 0.01-100 ng/mL, and recoveries ranging from 92.77 to 100.02% in pork and 92.26-101.23% in milk. Furthermore, the immunosensor exhibited good stability, reproducibility, and specificity in detecting TMC in pork and milk real samples.

High adsorption capacities for dyes by a pH-responsive sodium alginate/sodium lignosulfonate/carboxylated chitosan/polyethyleneimine adsorbent.

Dyes are indispensable for the rapid development of society, but untreated dye wastewater can threaten human health. In this study, an adsorbent (SA/SL/CCS/PEI@MNPs) was synthesized by one-pot method using magnetic nanoparticles (MNPs), sodium alginate (SA), sodium lignosulfonate (SL), carboxylated chitosan (CCS) and polyethyleneimine (PEI). The adsorbent was mesoporous micrometer-sized particles with pore size of 34.92 nm, which was favorable for dynamic column experiments. SA/SL/CCS/PEI@MNPs possessed pH-responsive performance. Under acidic condition, the maximum adsorption capacities for anionic dyes (tartrazine, reactive black-5, indigo carmine) reached >550 mg/g. Under alkaline condition, those for cationic dyes (methylene blue, methyl violet, neutral red) exceeded 1900 mg/g. The function of the various modifiers was investigated. The results indicated that the incorporation of SL, CCS and PEI was able to provide plenty of sulfonate, carboxylate and amino/imine reactive groups so that adsorption capacities of dyes were improved. The adsorption mechanism was explored by FTIR and XPS. At the same time, the adsorption mechanism was more deeply analyzed using molecular dynamics simulations and radial distribution function. It was demonstrated that the dyes adsorption on the SA/SL/CCS/PEI@MNPs was mainly due to electrostatic attraction and π-π interaction. In addition, the adsorbent had good reusability, and the removal still reached over 90 % after five cycles. In conclusion, the adsorbent displayed a broad prospect for the adsorption of organic dyes.