Polycationic Polymer Research Articles

Aggregation-induced emission (AIE) of Au(I)-GSH complexes activated by cationic polymer for sensitive foodborne pathogens detection and inactivation

Aggregation-induced emission (AIE) is a novel signal output method but is limited in pathogen sensing. Herein, a multifunctional biosensor based on the AIE properties of Au(I)-GSH complexes as signal conversion tags was firstly constructed for rapid and sensitive total bacteria. Bacteria were captured by the boronic acid group of MNPs@Au@4-MPBA (MAu@MPBA) through recognition of peptidoglycan on their surface. Simultaneously, cationic polymer Poly (diallyldimethylammonium chloride) (PDDA) were electrostatic absorb on bacteria. After magnetic separation, the remaining PDDA induced Au(I)-GSH complexes aggregation to produce strong red fluorescence, which was linearly with the quantity of bacteria. Under optimized conditions, quantitative detection of bacteria can be achieved within 60 min, with a minimum detection concentration of 18 CFU/mL. Moreover, 90 % bacteria can be effectively inactivated while being detected. This strategy is capable of sensitively detecting and killing foodborne pathogens and can be successfully applied to food safety monitoring.

Spleen Targeting Nucleic Acid Delivery Vector Based on Metal-Organic Frameworks.

Nucleic acids have attracted increasing attention as drugs due to their fascinating advantages, such as long-term efficacy and ease of preparation compared to proteins. The nucleic acid therapy relies heavily on delivery vectors, which can prevent the degradation of nucleic acids while assisting them in cellular internalization. However, commonly used nonviral vector liposomes easily accumulate in the liver, which can limit their application in extrahepatic diseases. Herein, a potential spleen targeting vector for nucleic acids is developed based on the metal-organic frameworks. The plasmids are encapsulated inside the nanoscale zeolitic imidazolate framework (ZIF) via coprecipitation. The co-encapsulation of the cationic polymer poly(ether imide) (PEI) and the stabilizer polyvinylpyrrolidone (PVP) can significantly improve particle dispersion and stability. The prepared nanoparticles allow efficient transfection in vitro, mainly through clathrin-mediated and caveolae-mediated endocytosis. The biodistribution in mice shows that 46% of the nanoparticles accumulate in the spleen, which is much higher than that of the liposomes. The vector can successfully deliver plasmids to extrahepatic organs for protein synthesis and even induce an immune response. The elaborate ZIF-based nanoparticle may offer a new route for extrahepatic, especially spleen targeting delivery for the nucleic acids.

Exploring the influence of polymers on soil ecosystems: prospective from agricultural contexts

The utilization of advanced polymeric materials has indeed emerged as a significant trend in sustainable agriculture, offering a range of innovative applications aimed at enhancing productivity, minimizing environmental impact, and promoting resource efficiency. Smart polymeric materials enable the controlled release of pesticides, herbicides, and fertilizers, thereby enhancing their efficacy while reducing the quantities needed. Superabsorbent polymeric materials act as soil conditioners, assisting in alleviating the negative impacts of drought by retaining moisture and enhancing soil structure. This fosters improved plant growth and resilience in water-scarce environments. Polycationic polymers play a role in plant bioengineering, facilitating genetic transformation processes aimed at enhancing crop productivity and disease resistance. Advanced polymeric systems contribute to the arsenal of precision agriculture tools by enabling precise delivery and targeted application of agricultural inputs. This approach enhances resource efficiency, reduces waste, and minimizes environmental impact while optimizing crop yields. In reviewing recent developments in the design and application of advanced polymeric systems for precision agriculture, several key considerations emerge.

Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era.

The recent success of gene therapy during the COVID-19 pandemic has underscored the importance of effective and safe delivery systems. Complementing lipid-based delivery systems, polymers present a promising alternative for gene delivery. Significant advances have been made in the recent past, with multiple clinical trials progressing beyond phase I and several companies actively working on polymeric delivery systems which provides assurance that polymeric carriers can soon achieve clinical translation. The massive advantage of structural tunability and vast chemical space of polymers is being actively leveraged to mitigate shortcomings of traditional polycationic polymers and improve the translatability of delivery systems. Tailored polymeric approaches for diverse nucleic acids and for specific subcellular targets are now being designed to improve therapeutic efficacy. This review describes the recent advances in polymer design for improved gene delivery by polyplexes and covalent polymer-nucleic acid conjugates. The review also offers a brief note on novel computational techniques for improved polymer design. The review concludes with an overview of the current state of polymeric gene therapies in the clinic as well as future directions on their translation to the clinic.

Protonation-triggered self-assembly of chiral copper nanoclusters: Chirality transfer and circularly polarized luminescence generation

Complex biological processes are inseparable from the transmission of chiral information, and the realization of chiral transfer in the process of designing and manufacturing chiral functional materials is conducive to explore sophisticated nature activities. The construction of chiral nanomaterials using self-assembly strategy can effectively constitute asymmetric molecular stacking pattern and occur hierarchical chirality transfer, but there are few studies on the chirality modulation or amplification of metal nanoclusters in self-assembled systems. Herein, we select a chiral glutathione-stabilized copper nanocluster (R-GSH-Cu NCs) as the chiral donor and introduced achiral cationic polymer poly (allylamine hydrochloride) (PAH) to self assembly to form R-GSH-Cu NCs/PAH nanoaggregates. Through thesynergistic effectof hydrogen bonding and electrostatic interaction. Through the synergistic effect of hydrogen bonding and electrostatic interaction, the optical properties of nanoaggregates were greatly regulated, especially in the supramolecular chirality and circularly polarized luminescence (CPL). Meanwhile, the addition of external proton source (hydrochloric acid, HCl) into the R-GSH-Cu NCs/PAH complexes increased the protonation degree of PAH, resulting in chiral inversion and CPL amplification. Regulating chiral properties of chiral metal NCs provides a nanoscale platform for understanding chiral transfer at organic–inorganic interface, which provided candidate in 3D display, biological probes, encrypted information transmission.

Intravenous delivery of STING agonists using acid-sensitive polycationic polymer-modified lipid nanoparticles for enhanced tumor immunotherapy

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Flexible automated system for laser modified layer by layer assembly.

An open-source automated system for laser modified layer by layer assembly is described. This flexible system, the first designed to be used with this process, can be used to fabricate a range of laser patterned, layer by layer thin films. The Arduino microcontroller-based system features a stepper motor-controlled turntable that holds solutions and water rinses for dipping. The substrate can be moved vertically to be dipped into each of the solutions throughout the process. A semiconductor laser is used to modify the thickness of the thin film during the chosen dipping cycles. Several aspects of the robotic system are easily controlled via software, including the average laser power, irradiation time, horizontal laser position, and vertical substrate position. The system is fully automated and, once started, does not require any user interaction. To demonstrate the capability of the automated system for patterning, electrochromic thin film devices using 50-bilayer laser patterned films using the polymers poly(allylamine hydrochloride) and sodium poly[2-(3-thienyl)-ethoxy-4-butylsulfonate] are presented. One device is patterned with the shape of a large "C," created by irradiating the sample (55 mW average power, 405nm) while the substrate was moved vertically up and down or the laser was moved horizontally. The laser irradiates the sample during only the dipping in the polycation polymer solution. A second electrochromic thin film device is based on a sample with five parallel laser patterned lines, where each line is fabricated with different average laser powers and, hence, different thicknesses. The thicknesses of the lines vary by about 30nm.

Near-infrared inducible supports in bio-catalysts design: A useful and versatile tool in enhancement of enzyme activity

Immobilized enzymes have encountered two main challenges: Reduced enzyme activity compared to free enzymes and exhausted immobilized enzymes due to reusability. Herein, we suggested a promising activity enhancement strategy to overcome these challenges. The emission from upconversion nanoparticles (UCNPs) under near-infrared (NIR) excitation can increase the activity of PEG-l-ASNase due to Förster Resonance Energy Transfer. For this purpose, UCNPs were initially synthesized using the hydrothermal method. Subsequently, these UCNPs were functionalized with a polycationic polymer, branched polyethyleneimine (PEI), and the immobilization of PEG-l-ASNase was achieved through adsorption. We preliminarily explored the parameters such as enzyme concentration, incubation time, pH, temperature, reusability, storage stability, and kinetic study, etc. Further, the in vitro biocompatibility, hemolytic behavior, and anticancer activity of the produced UCNPs were also analyzed as crucial parameters. The results showed the pH durance, thermal and storage stability of the immobilized PEG-l-ASNases were enhanced. The immobilized PEG-l-ASNases maintained their activity to ≥55 % after 20 cycles. Enzyme immobilization led to a decrease in Km and Vmax compared to PEG-l-ASNase. In vitro assays revealed that immobilized enzyme further reduced the proliferation of human leukemia cell line (HL-60) upon NIR irradiation exposure but did not cause toxicity. This research may provide a new strategy to promote the catalytic activity of l-ASNase and demonstrates its potential application on human leukemia cells. Finally, these outcomes are valuable for the use of NIR induction in enzymatic reactions.

L-Asparaginase Conjugates from the Hyperthermophilic Archaea Thermococcus sibiricus with Improved Biocatalytic Properties.

This study investigated the effect of polycationic and uncharged polymers (and oligomers) on the catalytic parameters and thermostability of L-asparaginase from Thermococcus sibiricus (TsA). This enzyme has potential applications in the food industry to decrease the formation of carcinogenic acrylamide during the processing of carbohydrate-containing products. Conjugation with the polyamines polyethylenimine and spermine (PEI and Spm) or polyethylene glycol (PEG) did not significantly affect the secondary structure of the enzyme. PEG contributes to the stabilization of the dimeric form of TsA, as shown by HPLC. Furthermore, neither polyamines nor PEG significantly affected the binding of the L-Asn substrate to TsA. The conjugates showed greater maximum activity at pH 7.5 and 85 °C, 10-50% more than for native TsA. The pH optima for both TsA-PEI and TsA-Spm conjugates were shifted to lower pH ranges from pH 10 (for the native enzyme) to pH 8.0. Additionally, the TsA-Spm conjugate exhibited the highest activity at pH 6.5-9.0 among all the samples. Furthermore, the temperature optimum for activity at pH 7.5 shifted from 90-95 °C to 80-85 °C for the conjugates. The thermal inactivation mechanism of TsA-PEG appeared to change, and no aggregation was observed in contrast to that of the native enzyme. This was visually confirmed and supported by the analysis of the CD spectra, which remained almost unchanged after heating the conjugate solution. These results suggest that TsA-PEG may be a more stable form of TsA, making it a potentially more suitable option for industrial use.

Time-Resolved Killing of Individual Bacterial Cells by a Polycationic Antimicrobial Polymer.

Polycationic polymers are widely studied antiseptics, and their efficacy is usually quantified by the solution concentration required to kill a fraction of a population of cells (e.g., by Minimum Bactericidal Concentration (MBC)). Here we describe how the response to a polycationic antimicrobial varies greatly among members of even a monoclonal population of bacteria bathed in a single common antimicrobial concentration. We use fluorescence microscopy to measure the adsorption of a labeled cationic polymer, polydiallyldimethylammmonium chloride (PDADMAC, Mw ≈ 4 × 105 g mol-1) and the time course of cell response via a cell permeability indicator for each member of an ensemble of either Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa cells. This is a departure from traditional methods of evaluating synthetic antimicrobials, which typically measure the overall response of a collection of cells at a particular time and therefore do not assess the diversity within a population. Cells typically die after they reach a threshold adsorption of PDADMAC, but not always. There is a substantial time lag of about 5-10 min between adsorption and death, and the time to die of an individual cell is well correlated with the rate of adsorption. The amount adsorbed and the time-to-die differ among species but follow a trend of more adsorption on more negatively charged species, as expected for a cationic polymer. The study of individual cells via time-lapse microscopy reveals additional details that are lost when measuring ensemble properties at a particular time.

Development of a label-free, sensitive gold nanoparticles-poly(adenine) aptasensing platform for colorimetric determination of aflatoxin B1 in corn.

In this work, a sensitive colorimetric bioassay method based on a poly(adenine) aptamer (polyA apt) and gold nanoparticles (AuNPs) was developed for the determination of aflatoxin B1 (AFB1). The polyA apt, adsorbed on the AuNPs, especially can bind to the analyte while deterring non-specific interactions. This nano aptasensor uses cationic polymer poly(diallyl dimethyl ammonium chloride) (PDDA), as an aggregating agent, to aggregate gold nanoparticles. PolyA apt-decorated gold nanoparticles (AuNPs/polyA apt) show resistance to PDDA-induced aggregation and maintains their dispersed state (red color) with the optical absorbance signal at λ = 520 nm. However, in the presence of AFB1 in the assay solution, the specific aptamer reacts with high affinity and folds into its three-dimensional form. Aggregation of AuNPs induced by PDDA caused their optical signal shift to λ = 620 nm (blue color). AFB1 concentration in the bioassay solution determines the amount of optical signal shift. Therefore, optical density ratio in two wavelengths (A620/520) can be used as a sturdy colorimetric signal to detect the concentration of aflatoxin B1. AFB1 was linearly detected between 0.5 and 20 ng mL-1, with a detection limit of 0.09 ng mL-1 (S/N = 3). The fabricated aptasensor was applied to the detection of AFB1 in real corn samples.

CRISPR/Cas9 Mutagenesis through Introducing a Nanoparticle Complex Made of a Cationic Polymer and Nucleic Acids into Maize Protoplasts.

Presently, targeted gene mutagenesis attracts increasing attention both in plant research and crop improvement. In these approaches, successes are largely dependent on the efficiency of the delivery of gene editing components into plant cells. Here, we report the optimization of the cationic polymer poly(2-hydroxypropylene imine) (PHPI)-mediated delivery of plasmid DNAs, or single-stranded oligonucleotides labelled with Cyanine3 (Cy3) or 6-Carboxyfluorescein (6-FAM)-fluorescent dyes into maize protoplasts. Co-delivery of the GFP-expressing plasmid and the Cy3-conjugated oligonucleotides has resulted in the cytoplasmic and nuclear accumulation of the green fluorescent protein and a preferential nuclear localization of oligonucleotides. We show the application of nanoparticle complexes, i.e., "polyplexes" that comprise cationic polymers and nucleic acids, for CRISPR/Cas9 editing of maize cells. Knocking out the functional EGFP gene in transgenic maize protoplasts was achieved through the co-delivery of plasmids encoding components of the editing factors Cas9 (pFGC-pcoCas9) and gRNA (pZmU3-gRNA) after complexing with a cationic polymer (PHPI). Several edited microcalli were identified based on the lack of a GFP fluorescence signal. Multi-base and single-base deletions in the EGFP gene were confirmed using Sanger sequencing. The presented results support the use of the PHPI cationic polymer in plant protoplast-mediated genome editing approaches.

Reversible Protection and Targeted Delivery of DNA Origami with a Disulfide-Containing Cationic Polymer.

DNA nanostructures have considerable biomedical potential as intracellular delivery vehicles as they are highly homogeneous and can be functionalized with high spatial resolution. However, challenges like instability under physiological conditions, limited cellular uptake, and lysosomal degradation limit their use. This paper presents a bio-reducible, cationic polymer poly(cystaminebisacrylamide-1,6-diaminohexane) (PCD) as a reversible DNA origami protector. PCD displays a stronger DNA affinity than other cationic polymers. DNA nanostructures with PCD protection are shielded from low salt conditions and DNase I degradation and show a 40-fold increase in cell-association when linked to targeting antibodies. Confocal microscopy reveals a potential secondary cell uptake mechanism, directly delivering the nanostructures to the cytoplasm. Additionally, PCD can be removed by cleaving its backbone disulfides using the intracellular reductant, glutathione. Finally, the application of these constructs is demonstrated for targeted delivery of a cytotoxic agent to cancer cells,which efficiently decreases their viability. The PCD protective agent that is reported here is a simple and efficient method for the stabilization of DNA origami structures. With the ability to deprotect the DNA nanostructures upon entry of the intracellular space, the possibility for the use of DNA origami in pharmaceutical applications is enhanced.

Bioimaging based on Poly(ethylenimine)-Coated Carbon Dots and Gold Nanoparticles for pH Sensing and Metal Enhanced Fluorescence.

When exposed to specific light wavelengths, carbon dots (CDs), which tend to be fluorescent, can emit colorful light. It provides them with a lot of adaptability for different applications including bioimaging, optoelectronics, and even environmental sensing. Poly(ethylenimine) (PEI) coated carbon dots (PEI-CDs) with a long emission wavelength were synthesized via the hydrothermal method. The resultant CDs show strong fluorescence with quantum yield up to 20.2%. The PEI-CDs exist with distinct pH-sensitive features with pH values in the range of 2-14. The optical characteristics of CDs are pH-responsive due to the presence of different amine groups on PEI, which is a functional polycationic polymer. One of the most widely employed nanoparticles for improving the fluorescence plasmonic characteristics of a nanocomposite is gold. Gold nanoparticles were coupled with PEI-CDs in this assay by using the EDC-NHS coupling to increase the photoluminescence property of the PEI-CDs by using the metal-enhanced fluorescence approach. In the presence of gold nanoparticles, the fluorescence is enhanced 5-6 times. The likely mechanism in our investigation was primarily derived from enhancement of the intrinsic radiative decay rate rather than the local electric field impact. Moreover, PEI-CDs can be used as a bioimaging agent, as these molecules are nontoxic to the cells, and the positively charged PEI-CDs have the potential for nuclear targeting, allowing for electrostatic contact with DNA in the nucleus. This finding will expand the application that the PEI-CDs can be used in the future for targeted imaging applications.

Anti-proliferative activity of chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) against human HT-29 colon cancer cells: in vitro study.

Oxypeucedanin (OPD) as a powerful anti-proliferative agent found in the Angelicae dahuricae has been used to suppress cancer cell growth. However, the hydrophobic chemical structure has limited its solubility and bio-accessibility. This is the first time OPD is encapsulated into a nano-liposomal structure and coated with poly-cationic chitosan polymer as the oxypeucedanin drug delivery system to evaluate its antioxidant and anti-colon cancer potential. The chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) were synthesized utilizing the thin-layer hydration method and characterized by FESEM, DLS, FTIR, and zeta potential analysis. The anti-cancer potential of COPD-NC was analyzed by measuring the cell survival rate (MTT assay) and studying the cellular death type (AO/PI staining) following the increased treatment concentrations of COPD-NC on the HT-29 colon cancer cell line. Moreover, the COPD-NCs' apoptotic activity was verified by analyzing Cas-3 and Cas-9 gene expression profiles. Finally, the COPD-NCs' antioxidant activity was evaluated by applying ABTS, DPPH, and FRAP antioxidant assays. The 258.26-nm COPD-NCs significantly inhibited the HT-29 colon cancer cells compared with the normal fibroblast HFF cells. The up-regulated Cas-3 and Cas-9 gene expression exhibited the COPD-NCs' apoptotic activity. Also, the COPD-NCs' apoptotic activity was verified by detecting the increased apoptotic bodies following the AO/PI fluorescent staining in the increased exposure doses of COPD-NCs. Ultimately, the COPD-NCs meaningfully inhibited the ABTS-DPPH radicals and exhibited an appropriate FRAP-reductive potential. The designed nanostructure for COPD-NCs significantly improved its antioxidant potential and selective cytotoxicity on human HT-29 human cancer cells, which makes them a safe selective natural drug delivery system. Therefore, the COPD-NCs can selectively induce apoptotic death in human HT-29 cancer cells and have the potential to be studied as an anti-colon cancer compound. However, further cancer and normal cell lines are required to verify their selective cytotoxicity.

Vitis Pedata Nanoformulation in the Management of Alloxan Induced Experimental Diabetes

Vitis pedata is a woody climber of the Vitaceae family with a multitude of pharmacological effects like anti-inflammatory, antibacterial, anti-nociceptive, anti-arthritic, anti-oxidant, astringent, and hemostatic qualities. The research targets to assess the anti-diabetic efficacy of Vitis pedata aqueous extract nanoformulation in alloxan-induced diabetes rats. Biocompatible polycationic polymer chitosan is used for nanoformulation development. The aqueous extract loaded chitosan nanoparticle formulation displayed a particle size of 186± 5.37 nm with a polydispersity index of 0.226 and zeta potential value of 23 ± 1.93 mV. The nanoformulations were assessed for its anti-diabetic properties in comparison to aqueous extracts for the first time by in- vivo methodologies. Several parameters like body weight, blood glucose level, blood and serum biomarkers, were examined. Changes in tissue histoarchitecture, liver glycogen content, oxidative stress response and antioxidant status were also studied. In diabetic rats, the nano-scale formulation significantly reduced blood glucose levels, glucose tolerance, lipid profiles, and serum biomarkers, comparable to the oral hypoglycemic medication glibenclamide. The restoration of antioxidant status and pancreatic histoarchitecture through by size assisted delivery may be related to the improved control of diabetes by the nanoformulation than the extract alone. The work marks the first report of Vitis pedata nanoformulation for diabetes management and can serve as a prelude for further preclinical/clinical evaluations.

B-259 Exocas-2 Rapid and Pure Isolation of Exosomes by Anionic Exchange using Magnetic Beads

Abstract Background Extracellular vesicles (EVs) are considered essential biomarkers in liquid biopsies. Despite intensive efforts aimed at employing EVs in a clinical setting, workable approaches are currently limited owing to the fact that EV-isolation technologies are still in a nascent stage. This study introduces a magnetic bead-based ion exchange platform for isolating EVs called ExoCAS-2 (exosome clustering and scattering). Owing to their negative charge, exosomes can easily adhere to magnetic beads coated with a polycationic polymer. Owing to the features of magnetic beads, exosomes can be easily processed via washing and elution steps and isolated with high purity and yield within 40 min. Methods Cationic salt is coated on the surface of magnetic beads with carboxyl group surface residues. Inject the cation coated magnetic bead (ExoCAS) into the plasma solution and incubate in 4°C for 30 minutes. By charge interaction, negative charged EVs are attached to the cationic beads. And then, pH 6 washing buffer and 1M NaCl elution buffer were used for EV isolation. Results The present results confirmed the isolation of exosomes through analyses of size distribution, morphology, surface and internal protein markers, and exosomal RNA. Compared with the commercially available methods, the proposed method showed superior performance in terms of key aspects, including operation time, purity, and recovery rate. Conclusion This highlights the potential of this magnetic bead-based ion exchange platform for isolating exosomes present in blood plasma.

Baicalin functionalized PEI-heparin carbon dots as cancer theranostic agent

The worldwide prevalence of cancer and its significantly rising risks with age have garnered the attention of nanotechnology for prompt detection and effective therapy with minimal or no adverse effects. In the current study, heparin (HP) polymer derived heteroatom (N, S-) co-doped CDs were synthesized using hydrothermal synthesis method to efficiently deliver natural anticancer compound baicalin (BA). Heparin carbon dots (HCDs) were passivated with polyethylenimine (PEI) to improve its fluorescence quantum yield. The surface passivation of CDs by polycationic PEI polymer not only facilitated loading of BA, but also played a crucial role in the pH-responsive drug delivery. The sustained release of BA (up to 80 %) in mildly acidic pH (5.5 and 6.5) conditions endorsed its drug delivery potential for cancer-specific microenvironments. BA-loaded PHCDs exhibited enhanced anticancer activity as compared to BA/PHCDs indicating the effectiveness of the nanoformulation, Furthermore, the flow cytometry analysis confirmed that BA-PHCDs treated cells were arrested in the G2/M phase of cell cycle and had a higher potential for apoptosis. Bioimaging study demonstrated the excellent cell penetration efficiency of PHCDs with complete cytoplasmic localization. All this evidence comprehensively demonstrates the potency of BA-loaded PHCDs as a nanotheranostic agent for cancer.

The antioxidant, anti-angiogenic, and anticancer impact of chitosan-coated herniarin-graphene oxide nanoparticles (CHG-NPs)

BackgroundHerniarin, a simple coumarin found in chamomile leaf rosettes is known as the oxidative stress protector. In the current study, herniarin was captured into Graphene oxide nanoparticles and coated with chitosan poly-cationic polymer to be used as a novel bio-compatible nano-drug delivery system and investigate its antioxidant, anti-angiogenic and anti-cancer impacts on human lung A549 cancer cells. MethodThe Chitosan-coated Herniarin-Graphene oxide nanoparticles (CHG-NPs) were designed, produced, and characterized utilizing DLS, FESEM, FTIR, and Zeta-potential analysis. The CHG-NPs’ antioxidant activity was analyzed by conducting ABTS and DPPH antioxidant assays. The CHG-NPs’ anti-angiogenic activity was analyzed by CAM assay and verified by measuring VEGF and VEGFR gene expression levels following their increased treatment doses by applying Q-PCR technique. Finally, the CHG-NPs’ cytotoxicity was studied in the human lung A549 cancer cells. ResultThe stable (+27.11 mV) 213.6-nm CHG-NPs significantly inhibited the ABTS/DPPH free radicals and exhibited antioxidant activity. The suppressed angiogenesis process in the CAM vessels was observed by detecting the decreased length/number of the vessels. Moreover, the down-regulated VEGF and VEGFR gene expression of the CAM blood vessels following the increased CHG-NPs treatment doses verified the nanoparticles’ anti-angiogenic potential. Finally, the CHG-NPs significantly exhibited a selective cytotoxic impact on human A549 cancer cells compared with the normal HFF cell line. ConclusionThe selective cytotoxicity, strong antioxidant activity, and significant anti-angiogenic property of the nano-scaled produced CHG-NPs make it an appropriate anticancer nano-drug delivery system. Therefore, the CHG-NPs have the potential to be used as a selective anti-lung cancer compound.

Novel Double Hybrid-Type Bone Cements Based on Calcium Phosphates, Chitosan and Citrus Pectin.

In this work, the influence of the liquid phase composition on the physicochemical properties of double hybrid-type bone substitutes was investigated. The solid phase of obtained biomicroconcretes was composed of highly reactive α-tricalcium phosphate powder (α-TCP) and hybrid hydroxyapatite/chitosan granules (HA/CTS). Various combinations of disodium phosphate (Na2HPO4) solution and citrus pectin gel were used as liquid phases. The novelty of this study is the development of double-hybrid materials with a dual setting system. The double hybrid phenomenon is due to the interactions between polycationic polymer (chitosan in hybrid granules) and polyanionic polymer (citrus pectin). The chemical and phase composition (FTIR, XRD), setting times (Gillmore needles), injectability, mechanical strength, microstructure (SEM) and chemical stability in vitro were studied. The setting times of obtained materials ranged from 4.5 to 30.5 min for initial and from 7.5 to 55.5 min for final setting times. The compressive strength varied from 5.75 to 13.24 MPa. By incorporating citrus pectin into the liquid phase of the materials, not only did it enhance their physicochemical properties, but it also resulted in the development of fully injectable materials featuring a dual setting system. It has been shown that the properties of materials can be controlled by using the appropriate ratio of citrus pectin in the liquid phase.