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New graphene-nickel gallate nanocomplex (G-M-Ni) was designed, synthesized and characterized to deal with the requirement of functional combustion catalyst based on investigations of combustion mechanisms of propellant, structural analysis of catalyst and simulation results of quantum mechanics. The positive effect of G-M-Ni is not only reflected in the significantly increased burning rate, but also reflected in the reduction of friction sensitivity of composite modified double base (CMDB) propellant. The G-M-Ni nanocomplex exhibited significantly enhanced catalytic performances, and the burning rate of propellant at 20 MPa enhanced from 23.15 to 29.07 mm·s−1. Besides, the friction sensitivity of propellant reduced from 64 % to 36 % after addition of 0.5% G-M-Ni. The positive effect of G-M-Ni on CMDB propellant combustion is mainly attributed to its promotion impact on nitroglycerin (NG) pyrolysis, which significantly increased the differential charge density and decreased the decomposition activation energy (from 1.89 eV to 1.38 eV). The gas products produced by the rapid pyrolysis of NG are conducive to the heat feedback between the gas phase and the combustion surface, which makes the propellant have higher burning rate, bright flame, thin dark zone and flocculated quenching surface morphology. The findings in this study confirm the potential of G-M-Ni as a functional combustion catalyst for CMDB propellants, which has guiding significance and inspiration for the development of new combustion catalysts from the view of molecular-level insights. Recently, graphene based functional combustion catalysts have attracted much attention in the field of solid propellants due to their excellent catalytic combustion performance, reduced sensitivity, and improved mechanical properties. Herein, novel graphene-nickel gallate nanocomplex (G-M-Ni) were designed, synthesized and characterized to deal with the to deal with the requirement of functional combustion catalyst based on investigations of combustion mechanisms of CMDB propellant, structural analysis of new material and simulation results of quantum mechanics. By taking graphene as the benchmark, the G-M-Ni nanocomplex exhibited significantly enhanced catalytic performances, and excellent effect on the reduction of friction sensitivity. The relationship between molecular structure of G-M-Ni and combustion characteristics of CMDB propellant were disclosed. The theory-driven design mode of this work may provide new pathways to tune combustion behaviors of CMDB propellants from the view of molecular-level insights. The relationship between molecular structure of G-M-Ni and combustion characteristics of CMDB propellant were disclosed from the view of molecular-level insights. [Display omitted] • Graphene-nickel gallate nanocomplex (G-M-Ni) was first investigated in CMDB propellant. • G-M-Ni is conducive to the combustion and safety performance of CMDB propellant. • Explored the structure-activity relationship of G-M-Ni at the molecular level. • The key catalytic step of catalyst for CMDB propellant combustion was suggested. [ABSTRACT FROM AUTHOR]

AMPs are neutral and small size component of the immune system and showed better activity for the treatment of tuberculosis. The present study aimed to complex nisin with carbohydrate to increase bioavailability and provide site-specific action at lungs via pulmonary route. Nanocomplexes were prepared by kneading method and then adsorbed on lactose for DPI formulation. Nanocomplex of nisin peptide with carbohydrate offered a better effect along with dose reduction was proved by using M. tuberculosis H37Ra (ATCC 25177). Nanocomplex proved to be an alternative delivery to conventional drug therapy for the treatment of tuberculosis. [ABSTRACT FROM AUTHOR]

Dennis To,1 Mariana Blanco Massani,1 Débora C Coraça-Huber,2 Anna Seybold,3 Fabrizio Ricci,1,4 Katrin Zöller,1 Andreas Bernkop-Schnürch1 1Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 2Research Laboratory for Implant Associated Infections (BIOFILM LAB), Experimental Orthopaedics, University Hospital for Orthopaedics and Traumatology, Medical University Innsbruck, Innsbruck, Austria; 3Department of Zoology, University of Innsbruck, Innsbruck, Austria; 4Thiomatrix Forschungs- und Beratungs GmbH, Innsbruck, AustriaCorrespondence: Andreas Bernkop-Schnürch, Email Andreas.Bernkop@uibk.ac.atPurpose: The eradication of bacterial biofilms poses an enormous challenge owing to the inherently low antibiotic susceptibility of the resident microbiota. The complexation of antibiotics with polyphosphate can substantially improve antimicrobial performance.Methods: Nanoparticular complexes of the model drug colistin and polyphosphate (CP-NPs) were developed and characterized in terms of their particle size and morphology, polydispersity index (PDI), zeta potential, and cytotoxicity. Enzyme-triggered monophosphate and colistin release from the CP-NPs was evaluated in the presence of alkaline phosphatase (AP). Subsequently, antimicrobial efficacy was assessed by inhibition experiments on planktonic cultures, as well as time-kill assays on biofilms formed by the model organism Micrococcus luteus.Results: The CP-NPs exhibited a spherical morphology with particle sizes < 200 nm, PDI < 0.25, and negative zeta potential. They showed reduced cytotoxicity toward two human cell lines and significantly decreased hemotoxicity compared with native colistin. Release experiments with AP verified the enzymatic cleavage of polyphosphate and subsequent release of monophosphate and colistin from CP-NPs. Although CP-NPs were ineffective against planktonic M. luteus cultures, they showed major activity against bacterial biofilms, outperforming native colistin treatment. Strongly elevated AP levels in the biofilm state were identified as a potential key factor for the observed findings.Conclusion: Accordingly, polyphosphate-based nanocomplexes represent a promising tool to tackle bacterial biofilm. Keywords: polyphosphate, colistin, antimicrobial, nanoparticle, nanocomplex

New graphene Schiff base iron nanocomplexes (S-792-Fe, S-550-Fe, and S-590-Fe) were designed and fabricated based on investigations of reactions mechanisms of AP pyrolysis, structural analysis of new materials and simulation results of quantum mechanics to deal with the long-standing contradiction between safety and performance for composite propellent combustion catalyst. By taking traditional catalyst Catocene as the benchmark, the S-550-Fe nanocomplexes exhibited competitive catalytic performances, much better anti-migration properties and significantly reduced impact and electrostatic sensitivities. After adding S-550-Fe, the burning rate of propellant enhanced from 13.87 to 19.77 mm s−1 at 15 MPa, and the impact and electrostatic sensitivities are improved to 50.2 cm and 172.12 mJ, respectively. The excellent catalytic performance of S-550-Fe is closely related to its molecular structure, which is manifested by an increase in charge density and a decrease in NH 3 oxidation energy barriers. The promotion effects of S-550-Fe on desorption and oxidation of NH 3 from the surface of AP is conducive to the rapid and complete pyrolysis of AP, which is reflected in the improvement of combustion rate and temperature gradient. The theory-driven design mode of this work may provide new pathways to tune combustion behaviors of composite propellants from the view of molecular-level insights. Effects and mechanisms of S-550-Fe on combustion and safety of AP-HTPB propellant were disclosed. [Display omitted] • Graphen Schiff base Fe nanocomplexes were first investigated in AP-HTPB propellant. • S-550-Fe is conducive to the combustion and safety performance of AP-HTPB propellant. • The structure-activity relationship of S-550-Fe at the molecular level was explored. • The influence of catalysts on NH 3 oxidation process was revealed. [ABSTRACT FROM AUTHOR]

Background: Acquired Immunodeficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV) was initially associated with rapid disease progression and high mortality rates. However, advances in drug delivery systems have aimed to optimize therapeutic outcomes, especially for medications facing challenges such as toxicity, uneven distribution, instability and formulation complexities. Materials and Methods: In this study, we introduce TCS-PEG/MMT composites, a novel formulation designed for antiretroviral activity. This formulation consists of a blend of Medical clay (MMT) and Thiolated Chitosan and Polyethylene Glycol (TCS-PEG), which are biodegradable materials. Using Design Expert software, we optimized the loading procedure of lamivudine onto chitosan (X1), MMT (X2) and PEG (X3) to achieve desired Entrapment Efficacy (EE) and particle size (PS). The desirability technique helped determine an optimal formulation with 3 g of chitosan, 3 g of MMT and 2.5 g of PEG. Results: The optimized formulation exhibited an EE of 79.58% and a PS of 592.32 nm. We conducted comprehensive analyses on the Optimized formulation (O-LMD-NC), including assessments of swelling characteristics, surface morphology, drug loading, entrapment efficiency and particle size. Water absorption of O-LMD-NC samples gradually increased over time, reaching a maximum of 13.5 g/g after 24 hr. In vitro drug release studies confirmed sustained release of lamivudine over a 24 hr period. Conclusion: Our findings suggest that LMD-loaded polymeric nanocomposites offer a promising approach to enhance the efficacy of AIDS treatment. [ABSTRACT FROM AUTHOR]

Yun Liu,1,2 Timo Hamm,3 Thomas Ralf Eichinger,3 Walter Kamm,3 Heike Andrea Wieland,3 Brigitta Loretz,1 Anna KH Hirsch,2,4 Sangeun Lee,1,2 Claus-Michael Lehr1,2 1Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany; 2Department of Pharmacy, Saarland University, Saarbrücken, Germany; 3Department of Research and Development, Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany; 4Department of Drug Design and Optimisation, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, GermanyCorrespondence: Claus-Michael Lehr, Department of Drug Delivery Across Biological Barriers, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany, Tel +49 681 98806-1000, Fax +49 681 98806 1009, Email Claus-Michael.Lehr@helmholtz-hips.de Sangeun Lee, Department of Pharmacy, Saarland University, Saarbrücken, Germany, Tel +49 681 302 4764, Fax +49 681 302 2028, Email Sangeun.Lee@uni-saarland.deBackground: Therapeutic proteins and peptides offer great advantages compared to traditional synthetic molecular drugs. However, stable protein loading and precise control of protein release pose significant challenges due to the extensive range of physicochemical properties inherent to proteins. The development of a comprehensive protein delivery strategy becomes imperative accounting for the diverse nature of therapeutic proteins.Methods: Biodynamers are amphiphilic proteoid dynamic polymers consisting of amino acid derivatives connected through pH-responsive dynamic covalent chemistry. Taking advantage of the amphiphilic nature of the biodynamers, PNCs and DEs were possible to be prepared and investigated to compare the delivery efficiency in drug loading, stability, and cell uptake.Results: As a result, the optimized PNCs showed 3-fold encapsulation (< 90%) and 5-fold loading capacity (30%) compared to DE-NPs. PNCs enhanced the delivery efficiency into the cells but aggregated easily on the cell membrane due to the limited stability. Although DE-NPs were limited in loading capacity compared to PNCs, they exhibit superior adaptability in stability and capacity for delivering a wider range of proteins compared to PNCs.Conclusion: Our study highlights the potential of formulating both PNCs and DE-NPs using the same biodynamers, providing a comparative view on protein delivery efficacy using formulation methods. Keywords: amphiphilic polymer, nanocomplex, double emulsion, pH-responsive, protein delivery, dynamic covalent chemistry

The application of nanotechnology in biological and medical fields have resulted in the creation of new devices, supramolecular systems, structures, complexes, and composites. Dendrimers are relatively new nanotechnological polymers with unique features; they are globular in shape, with a topological structure formed by monomeric subunit branches diverging to the sides from the central nucleus. This review analyzes the main features of dendrimers and their applications in biology and medicine regarding cancer treatment. Dendrimers have applications that include drug and gene carriers, antioxidant agents, imaging agents, and adjuvants, but importantly, dendrimers can create complex nanosized constructions that combine features such as drug/gene carriers and imaging agents. Dendrimer‐based nanosystems include different metals that enhance oxidative stress, polyethylene glycol to provide biosafety, an imaging agent (a fluorescent, radioactive, magnetic resonance imaging probe), a drug or/and nucleic acid that provides a single or dual action on cells or tissues. One of major benefit of dendrimers is their easy release from the body (in contrast to metal nanoparticles, fullerenes, and carbon nanotubes), allowing the creation of biosafe constructions. Some dendrimers are already clinically approved and are being used as drugs, but many nanocomplexes are currently being studied for clinical practice. In summary, dendrimers are very useful tool in the creation of complex nanoconstructions for personalized nanomedicine. This article is categorized under:Diagnostic Tools > Diagnostic NanodevicesDiagnostic Tools > In Vivo Nanodiagnostics and ImagingTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease [ABSTRACT FROM AUTHOR]

Aim. The goal of the study is to demonstrate the binding sites for curcumin on the protein carriers - bovine serum albumin and diphtheria toxoid CRM197. BSA was chosen as a potential non-specific protein carrier because of its widely used in medicine as a drug carrier. Methods. In the investigation, both spectrophotometric and molecular docking methods were used. Results. Two stable binding sites were demonstrated for BSA to bind curcumin. CRM197 was taken as a well-studied carrier protein with its own antitumor activity and has been investigated as a specific carrier with a high affinity for cancer cells with overexpression of epidermal growth factor receptor. Our results showed one possible curcumin binding site, making CRM197 an ideal specific curcumin delivery platform that provides at least an additive effect in anticancer therapies. Conclusions. In conclusion, both studied proteins form stable complexes with curcumin that can lay in base of the commercial drug application.

Acute myeloid leukemia carrying FMS-like tyrosine kinase receptor-3 (FLT3) mutations is a fatal blood cancer with a poor prognosis. Although the FLT3 inhibitor gilteritinib has recently been approved, it still suffers from limited efficacy and relatively high nonresponse rates. In this study, we report the potentiation of gilteritinib efficacy using nanocomplexation with a hyaluronic acid–epigallocatechin gallate conjugate. The self-assembly, colloidal stability, and gilteritinib loading capacity of the nanocomplex were characterized by reversed-phase high-performance liquid chromatography and dynamic light scattering technique. Flow cytometric analysis revealed that the nanocomplex efficiently internalized into FLT3-mutated leukemic cells via specific interactions between the surface-exposed hyaluronic acid and CD44 receptor overexpressed on the cells. Moreover, this nanocomplex was found to induce an eradication of the leukemic cells in a synergistic manner by elevating the levels of reactive oxygen species and caspase-3/7 activities more effectively than free gilteritinib. This study may provide a useful strategy to design nanomedicines capable of augmenting the therapeutic efficacy of FLT3 inhibitors for effective leukemia therapy. [ABSTRACT FROM AUTHOR]

Mesoporous polydopamine (MPDA) nanoparticles were prepared using a template method to address the difficulty in accumulation of nitric oxide gas in tumor sites. Arginine-IR780-mesoporous polydopamine nanocomposites (AI-MPDA) loaded with L-arginine (L-Arg) and photosensitizer IR780 were obtained to generate NO in situ in tumor area. The properties of the nanocomposites were characterized by transmission electron microscopy, ultraviolet spectrophotometer, in vitro cell uptake, NO fluorescence staining etc. The results show that the MPDA nanoparticles are spherical with a relatively obvious mesoporous structure, and the specific area is 40.80 m²/g. The particle size of AIMPDA is about 200 nm, which can be effectively taken up by human osteosarcoma (143B) cells and achieve the in situ release of NO. [ABSTRACT FROM AUTHOR]

ABSTRACT: Introduction. Currently, wood-polymer compositions (WPC) are widely used in the national economy and construction. The composition of WPC varies widely depending on the further purpose. Improving the binding quality in the wood-polymer system is one of the promising areas for enhancing operational characteristics. Organic and inorganic substrates nanostructured with individual substances, including metal particles, are used as binding components. In the petrochemical industry, most high-capacity productions use catalysts based on active carriers like heavy metals when developing targeted products for various purposes. After several stages of regeneration, recovering these heavy metals becomes impossible. Consequently, spent catalysts accumulate in sedimentation tanks and sludge collectors, lacking an efficient method for disposal and secondary use. One of the components included in the composition of spent catalysts is chromium (+6), which belongs to carcinogenic metals. Numerous disposal methods are currently inadequate for neutralizing this metal on an industrial scale, which is of interest for research. Methods and materials. The study is aimed at converting carcinogenic chromium (+6) into non-carcinogenic chromium (+3) by ultrahigh frequency exposure (microwave), which will open up opportunities for its use as a chromium-containing nanocomplex binding a tree-polymer. Results and discussions. The ultrahigh-frequency effect on the mixture of wood-polymer composition and spent chromium (+6) causes an increase in the penetration depth of high–frequency waves, characterized by a uniform distribution of energy over the entire area of the composite, which is explained by the reduction of chromium (VI) oxide into chromium (III) oxide, and there is also a change in the color of the nanostructured wood-polymer composition (WP – compositions) from yellow to malachite. Conclusion. This study, which consists in the application of microwave exposure to the wood-nanoparticle-polymer system, confirms the receipt of a durable construction product and its use in the construction of roofs, facade boards, sidewalks, piers, port facilities, etc

Zhiqiang He,1 Huan Yang,1 Yufan Gu,1 Yuhan Xie,1 Jianan Wu,1 Chen Wu,1 Jiawei Song,1 Maofang Zhao,2,3 Da Zong,1 Wenlong Du,1 Jiaju Qiao,1 Yipeng Pang,1– 3 Yi Liu1– 3 1Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 2School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China; 3Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of ChinaCorrespondence: Yi Liu; Yipeng Pang, Department of Biophysics, School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262084, Email cbpeliuyinew@163.com; pangyipeng.xzmu@foxmail.comPurpose: Herein, an emerging drug delivery system was constructed based on zeolite imidazole backbone (ZIF-8) to improve antibacterial defects of nanosilver (AgNPs), such as easily precipitated and highly cytotoxic.Methods: The homogeneous dispersion of AgNPs on ZIF-8 was confirmed by UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM. The appropriate AgNPs loading ratio on ZIF-8 was screened through the cell and antibacterial experiments based on biosafety and antibacterial performance. The optimal environment for AgNPs@ZIF-8 to exert antibacterial performance was probed in the context of bacterial communities under different acid-base conditions. The potential mechanism of AgNPs@ZIF-8 to inhibit the common clinical strains was investigated by observing the biofilm metabolic activity and the level of reactive oxygen species (ROS) in bacteria.Results: The successful piggybacking of AgNPs by ZIF-8 was confirmed using UV-Vis spectroscopy, FTIR spectroscopy, particle size analysis, zeta potential analysis, and SEM characterization methods. Based on the bacterial growth curve (0– 24 hours), the antibacterial ability of AgNPs@ZIF-8 was found to be superior to AgNPs. When the mass ratio of ZIF-8 and AgNPs was 1:0.25, the selection of AgNPs@ZIF-8 was based on its superior antimicrobial efficacy and enhanced biocompatibility. Notably, under weakly acidic bacterial microenvironments (pH=6.4), AgNPs@ZIF-8 demonstrated a more satisfactory antibacterial effect. In addition, experiments on biofilms showed that concentrations of AgNPs@ZIF-8 exceeding 1×MIC resulted in more than 50% biofilm removal. The nanomedicine was found to increase ROS levels upon detecting the ROS concentration in bacteria.Conclusion: Novel nanocomposites consisting of low cytotoxicity drug carrier ZIF-8 loaded with AgNPs exhibited enhanced antimicrobial effects compared to AgNPs alone. The pH-responsive nano drug delivery system, AgNPs@ZIF-8, exhibited superior antimicrobial activity in a mildly acidic environment. Moreover, AgNPs@ZIF-8 effectively eradicated pathogenic bacterial biofilms and elevated the intracellular level of ROS.Graphical Abstract: Keywords: MOF, ZIF-8, AgNPs, nanocomplex, ROS, pathogenic biofilm

BACKGROUND: Walnut proteins display poor solubility and dispersity under acidic pH conditions, which limits their application in acidic beverages and foods. This study aimed to fabricate stable nanocomplexes between phosphorylated walnut protein (PWPI) and chitosan (CS) in an acidic pH and to investigate the encapsulation capacity of the complexes. RESULTS: The PWPI/CS nanocomplexes prepared at a mass ratio of 2:1 showed small Z‐average sizes (approximately 285 nm at pH 5.5 and 222 nm at pH 3.5) with a narrow particle distribution (polydispersity index <0.3). Caffeic acid phenethyl ester (CAPE) can be effectively encapsulated into PWPI/CS with improved solubility. Circular dichroism analysis indicated that PWPI/CS and CAPE‐loaded PWPI/CS (PWPI/CS‐CAPE) had reduced α‐helical content and increased β‐sheet content. Fourier transform infrared spectroscopy analysis further identified the different driving forces for the complexation of PWPI and CS at pH 3.5 and 5.5 and confirmed the successful encapsulation of CAPE. The rheological results revealed that the PWPI/CS and PWPI/CS‐CAPE formed at pH 3.5 (PWPI/CS‐CAPE‐3.5) had a higher apparent viscosity and better viscoelasticity than the complexes formed at pH 5.5. The PWPI/CS‐CAPE‐3.5 also showed good stability under heat treatment, salt treatment, and long‐term storage. The PWPI/CS‐CAPE complexes showed controlled release of CAPE. CONCLUSION: Walnut protein and chitosan nanocomplexes prepared at acidic pH levels were stable and promising carriers for CAPE, which could expand the application of walnut proteins in the food industry. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research was to employ maltodextrin as a stabilizer to stabilize the zein nanocomplex of paliperidone palmitate. Method: A zein-maltodextrin nanocomplex was synthesized using an anti-solvent precipitation technique. Box–Behnken Design was utilized for the optimization of drug-loaded zein-maltodextrin nanocomplex. Physiochemical characterization (DSC, XRD, NMR, and FT-IR), surface morphology, and release behavior were carried out. Results: The inclusion of polysaccharides resulted in spherical stable optimized nanocomplexes with a small particle size (184.30 ± 0.067 nm) and an acceptable zeta potential (23.00 ± 0.124 mV) and improved encapsulation. The solid-state characterization and zeta potential demonstrated that electrostatic interaction was the predominant driving force, with hydrogen bonding and hydrophobic interaction serving as additional driving forces. The release profile of drug-loaded zein-maltodextrin nanocomplex indicated sustained release in vitro. In long-term storage (25 ± 2 °C/60 ± 5% RH and 4 ± 2 °C), the drug-loaded zein-maltodextrin nanocomplex remained stable. Conclusion: Thus, the protein-polysaccharide nanocomplex can be used to deliver antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Numerous natural compounds exhibit low bioavailability due to suboptimal water solubility. The solubilization methods of the modern pharmaceutical industry in contemporary pharmaceutical research are restricted by low efficiency, sophisticated technological requirements, and latent adverse effects. There is a pressing need to elucidate and implement a novel solubilizer to ameliorate these challenges. This study identified natural biomass-derived carbon dots as a promising candidate. We report on natural fluorescent carbon dots derived from Aurantia Fructus Immatures (AFI-CDs), which have exhibited a remarkable solubilization effect, augmenting naringin (NA) solubility by a factor of 216.72. Subsequent analyses suggest that the solubilization mechanism is potentially contingent upon the oration of a nanostructured complex (NA-AFI-CDs) between AFI-CDs and NA, mediated by intermolecular non-covalent bonds. Concomitantly, the synthesized NA-AFI-CDs demonstrated high biocompatibility, exceptional stability, and dispersion. In addition, NA-AFI-CDs manifested superior free radical scavenging capacity. This research contributes foundational insights into the solubilization mechanism of naringin-utilizing AFI-CDs and proffers a novel strategy that circumvents the challenges associated with the low aqueous solubility of water-insoluble drugs in the field of modern pharmaceutical science.

Introduction: Breast cancer is a significant cause of mortality in women globally, and current treatment approaches face challenges due to side effects and drug resistance. Nanotechnology offers promising solutions by enabling targeted drug delivery and minimizing toxicity to normal tissues.Methods: In this study, we developed a composite platform called (Alg-AgNPs-CisPt), consisting of silver nanoparticles coated with an alginate hydrogel embedding cisplatin. We examined the effectiveness of this nanocomplex in induce synergistic cytotoxic effects on breast cancer cells.Results and Discussion: Characterization using various analytical techniques confirmed the composition of the nanocomplex and the distribution of its components. Cytotoxicity assays and apoptosis analysis demonstrated that the nanocomplex exhibited greater efficacy against breast cancer cells compared to AgNPs or cisplatin as standalone treatments. Moreover, the nanocomplex was found to enhance intracellular reactive oxygen species levels, further validating its efficacy. The synergistic action of the nanocomplex constituents offers potential advantages in reducing side effects associated with higher doses of cisplatin as a standalone treatment. Overall, this study highlights the potential of the (Alg-AgNPs-CisPt) nanocomplex as a promising platform embedding components with synergistic action against breast cancer cells.

Electrochemical water splitting is one of the ways to produce clean energy. However, oxygen evolution reaction (OER), an important half-reaction involving complex four-electron transfer, significantly reduces the overall water splitting efficiesncy. Tn this paper, by means of interface engineering. Ni(OH)2/CeO2 hybrid particles were modified with Nis nanosheet arrays grown in situ on nickel foam (NF) by electrodeposition, so as to successfully prepare an efficient and stable OER composite electrode. Scanning electron microscopy (SEM), X-ray diffraction (XRT)) and X-ray photoelectron spectroscopy (XPS) were used to characterize and analyze the microstructure, phase composition and surface element valence of the electrode materials. Tn the 1.0 M KOH electrolyte, the overpotential required to drive the current density of 100 mA/cm² is only 330 mV, the Tafel slope is 150.7 mV/dec, and the durability can be maintained for at least 25 h. The excellent electrocatalytic performance is due to the synergistic catalytic effect of Ni(0H)2/CeO2 particles and Nis nanoarray and the promotion of Ce1+ cations on the formation of OER active components. This study confirms that rare earth compounds have certain potential in modifying sulfide catalysts and can be widely used in the field of energy catalysis. [ABSTRACT FROM AUTHOR]

Although the etoposide and carboplatin (EP) combination strategy has been the first-line chemotherapy, patients with extensive-stage disease small-cell lung cancer (SCLC) still have poor survival outcomes. Our retrospective analysis revealed that 46 patients with SCLC only achieved medium overall survival (OS) of 11.6 months after treated by EP. Recently, it was demonstrated that combination therapy of PD1/PD-L1 immune checkpoint blocker and EP could significantly improve the OS of SCLC patients. However, the serious treatment-related toxicity leaded to a high rate of treatment-discontinuation or even death. In the present study, we have developed a novel TPP1-conjugated nanocomplex, abbreviated as TPP1NP-EP, which was co-loaded with carboplatin (CBP) and etoposide (VP16). The TPP1 was a PD-L1 targeting peptide and conjugated on the surface of nanocomplex by a matrix metalloproteinase (MMP-2/9)-cleavable peptide linker sequence PLGLAG. For dual-loading of CBP and VP16, the CBP was chemically conjugated with poly(ethylene glycol) (PEG)–poly(caprolactone) (PCL) by pH-sensitive hydrazone bond and the VP16 was physically encapsulated by emulsion-solvent evaporation method. In vitro and in vivo experiments demonstrated an excellent anti-tumor effect of TPP1NP-EP on SCLC and improved safety. In conclusion, the present study has provided a promising strategy for treatment of malignant SCLC.

The rational design and fabrication of edible codelivery carriers are important to develop functional foods fortified with a plurality of bioactive agents, which may produce synergistic effects in increasing bioactivity and functionality to target specific health benefits. Food proteins possess considerable functional attributes that make them suitable for the delivery of a single bioactive agent in a wide range of platforms. Among the different types of protein‐based carriers, protein–ligand nanocomplexes, micro/nanoparticles, and oil‐in‐water (O/W) emulsions have increasingly attracted attention in the codelivery of multiple bioactive agents, due to the simple and convenient preparation procedure, high stability, matrix compatibility, and dosage flexibility. However, the successful codelivery of bioactive agents with diverse physicochemical properties by using these simple‐structure carriers is a daunting task. In this review, some effective strategies such as combined functional properties of proteins, self‐assembly, composite, layer‐by‐layer, and interfacial engineering are introduced to redesign the carrier structure and explore the encapsulation of multiple bioactive agents. It then highlights success stories and challenges in the co‐encapsulation of multiple bioactive agents within protein‐based carriers with a simple structure. The partition, protection, and release of bioactive agents in these protein‐based codelivery carriers are considered and discussed. Finally, safety and application as well as challenges of co‐encapsulated bioactive agents in the food industry are also discussed. This work provides a state‐of‐the‐art overview of protein‐based particles and O/W emulsions in co‐encapsulating bioactive agents, which is essential for the design and development of novel functional foods containing multiple bioactive agents. [ABSTRACT FROM AUTHOR]

Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) in the liver due to chronic injuries and inflammation. These injuries activate and transform quiescent hepatic stellate cells (HSCs) into proliferative myofibroblast-like cells, which are the key contributors to the secretin of ECM in the fibrotic liver. The insulin-like growth factor 2 receptor (IGF2R) is a multifunctional receptor that is overexpressed on activated HSCs and is a specific molecular marker of activated HSCs in the fibrotic liver. We recently discovered an IGF2R-specific peptide that significantly increases the binding affinity and uptake of a protein-based siRNA nanocomplex to activated HSCs. However, there is a potential concern about the immunogenicity of protein-based siRNA delivery systems. In this study, we used the IGF2R-specific peptide to modify a small peptide-based siRNA nanocomplex for HSC-specific drug delivery. We incorporated a short spacer and glutamate residues into the IGF2R peptides. The siRNA nanocomplex modified with the IGF2R-3GK6E peptide demonstrated higher HSC specificity compared to an unmodified nanocomplex. This peptide-based nanocomplex provides a promising platform to effectively deliver Pcbp2 siRNA to activated HSCs for the treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Summary: Probiotics play essential roles in immune modulation. Combining probiotics with cancer vaccines potentially can achieve a synergistic effect. To maximize the efficacy of probiotics, proper probiotics formulation is necessary. Herein, Lactobacillus rhamnosus and Bifidobacterium longum are coated with lipid membrane to achieve the goal of losing less activity and bettering colonization in colon. In the subcutaneous transplanted colon cancer mouse model, probiotics formulation showed potent preventive and therapeutic efficacy, and the efficacy could be further improved by combining with cancer nanovaccines. Probiotics formulation can perform as immune adjuvants to enhance the innate immune response or as in-situ cancer vaccines. In the study of preventing chemical-induced orthotopic colon cancer model, probiotics formulation alone efficiently reduced tumor number in colon and the efficacy is improved by combining with cancer nanovaccines. All in all, the studies demonstrated that probiotics formulation can assist to maximize the efficacy of cancer nanovaccines.

Acute myeloid leukemia carrying FMS-like tyrosine kinase receptor-3 (FLT3) mutations is a fatal blood cancer with a poor prognosis. Although the FLT3 inhibitor gilteritinib has recently been approved, it still suffers from limited efficacy and relatively high nonresponse rates. In this study, we report the potentiation of gilteritinib efficacy using nanocomplexation with a hyaluronic acid–epigallocatechin gallate conjugate. The self-assembly, colloidal stability, and gilteritinib loading capacity of the nanocomplex were characterized by reversed-phase high-performance liquid chromatography and dynamic light scattering technique. Flow cytometric analysis revealed that the nanocomplex efficiently internalized into FLT3-mutated leukemic cells via specific interactions between the surface-exposed hyaluronic acid and CD44 receptor overexpressed on the cells. Moreover, this nanocomplex was found to induce an eradication of the leukemic cells in a synergistic manner by elevating the levels of reactive oxygen species and caspase-3/7 activities more effectively than free gilteritinib. This study may provide a useful strategy to design nanomedicines capable of augmenting the therapeutic efficacy of FLT3 inhibitors for effective leukemia therapy.

Vitamin D3 is a fat-soluble vitamin and one of the most important vitamins for body. Enriching foods, especially juices, with this vitamin requires encapsulation due to dispersion problems and sensitivity to oxidation and light. Therefore, in the present study, the effect of using zein hydrolysate and the effect of ultrasonic frequency (40 kHz) on the structure of nanocomplex carrying vitamin D3 and its stability in orange juice were investigated. The encapsulation and loading efficiency as well as the size of the prepared nanoparticles were measured and physicochemical, microbial and sensory evaluations were performed on the juice during days 1, 15 and 30. Encapsulation and loading efficiency for nanoparticles containing vitamin D3 by ultrasonic pretreatment increased by about 12.2 (70 vs. 62.4) and 14.73% (10.69 vs. 9.32), respectively. Particle size and zeta potential for different treatments were respectively obtained in the range of 49.59–58.49 nm and -24.5 – -36.62 and the use of nanocomplexes reduced the particle size and zeta potential compared to free vitamin D3 in orange juice. Regarding the physicochemical, microbial and sensory results obtained for fortified orange juice, zein hydrolysate nanocomplex has the potential to be used as a suitable and valuable carrier for enriching fruit juices with bioactive substances, especially vitamin D3, without any harmful effects. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the major challenges for the treatment of acute myeloid leukemia. Epigallocatechin gallate (EGCG), a bioactive polyphenol from green tea, has attracted immense interest as a potential chemosensitizer, but its application is limited due to the need for effective formulations capable of co-delivering EGCG and anti-leukemic drugs. Herein, we describe the formation and characterization of a micellar nanocomplex self-assembled from EGCG and daunorubicin, an anthracycline drug for the first-line treatment of acute myeloid leukemia. This nanocomplex was highly stable at pH 7.4 but stimulated to release the incorporated daunorubicin at pH 5.5, mimicking an acidic endosomal environment. More importantly, the nanocomplex exhibited superior cytotoxic efficacy against multidrug-resistant human leukemia cells over free daunorubicin by achieving a strong synergism, as supported by median-effect plot analysis. The observed chemosensitizing effect was in association with enhanced nucleus accumulation of daunorubicin, elevation of intracellular reactive oxygen species and caspase-mediated apoptosis induction. Our study presents a promising strategy for circumventing chemoresistance for more effective leukemia therapy. [ABSTRACT FROM AUTHOR]

This study fabricated novel smart colorimetric film from pullulan (P) and sodium alginate (SA) incorporated with anthocyanin (ACNs) loaded casein carboxymethylcellulose (CAS-CMC-ACNs) nanocomplex for the freshness monitoring of the fish and shrimp. The ACNs loaded nanocomplex exhibited large particle size (176.902 ± 4.641 nm) than CAS-CMC (155.454 ± 4.152 nm) nanocomplex without ACNs, and can be loaded in P/SA film with uniform distribution. The P/SA film incorporated with CAS-CMC-ACNs nanocomplex had a more compact structure, improved barrier properties, mechanical strength, and thermal stability than P/SA film incorporated with free ACNs, which could be attributed to hydrogen bonding among the components in the film matrix, as confirmed by SEM micrographs and FT-IR. Intriguingly, the composite film exhibited antibacterial effect against gram-negative bacteria E. coli (Escherichia coli) and gram-positive bacteria S. aureus (Staphylococcus aureus) with inhibition zone of 7 ± 0.283 mm and 8.6 ± 0.141 mm, and antioxidant effect. The composite film demonstrated a visible response to CO 2 and pH buffer. Furthermore, the composite smart film demonstrated the potential to monitor the freshness of fish and shrimp stored at 25 °C for 24 h via a visual color change from pink to dark grey. The findings revealed that the fabricated film is an effective tool for evaluating the freshness of fish and shrimp. [Display omitted] • Smart colorimetric film with ACNs-loaded CAS-CMC nanocomplexes and P/SA matrix. • ACNs were stabilized by CAS-CMC nanocomplexes as a pH indicator. • The P/SA/CAS-CMC-ACNs film showed superior physical properties. • The Colorimetric smart film had a potential used for seafood spoilage indicator. [ABSTRACT FROM AUTHOR]

Summary: Hybrid materials based on inorganic nanocrystals with organic polymers feature peculiar and fascinating properties and various applications. However, there is still a need for simple synthesis procedures that provide precise control over the polymer/nanocrystal microstructure of these materials. Herein, a novel organometallic approach to polymer-coated ZnO nanocrystals was developed. The presented method merges the initial ring-opening polymerization of ϵ-caprolactone mediated by an organozinc alkoxide initiator and an air-promoted transformation of the resulting macromolecular organozinc species. This one-pot procedure results in quantum-sized ZnO crystals with a core diameter of ca 3 nm coated by poly(ϵ-caprolactone) covalently bonded to the surface. Overall, the ability to create well-defined hybrid composites should provide a unique ability to access various nanosystems.

Copper (Ⅱ) theophylline [Cu(THP)2(H2O)4] complex in nanoscale has synthesized by ultrasonic sonication method. This method was used in the development of smaller, dispersed, and unaggregated nanoparticles (NPs). The structure of nanocomplex was described and suggested by the molar conductance, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), solubility, atomic fire absorption, and C.H.N. elemental analysis as octahedral geometry. The size and morphology of nanocomplex measured by transmission electron microscopy (TEM) were 20 nm. The nanocomplex was studied on phosphodiesterase enzyme activity in human serum of Iraqi patient?s asthma disease. The results showed a highly significant (p < 0.01) increase in the serum levels of phosphodiesterase enzyme activity in asthma patients (mean = 14.939 ± 3.021 ng/mL) compared with a control group (mean = 9.974 ± 2.032 ng/mL). The result also showed a highly significant (p < 0.01) decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with theophylline (mean = 11.253 ± 2.479 ng/mL) compared to serum patients without nano and control groups. It is vital that the result showed a highly significant (p < 0.01) decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with copper nano complex (mean = 9.563 ± 2.082 ng/mL) compared in patients of asthma disease with and without theophylline. As for comparing asthma disease with copper nano complex and control group, the result showed there was no significant effect (p > 0.05).

Cancer vaccines that make use of tumor antigens represent a promising therapeutic strategy by stimulating immune responses against tumors to generate long-term anti-tumor immunity. However, vaccines have shown limited clinical efficacy due to inefficient delivery. In this study, we focus on vaccine delivery assisted by nanocomplexes for cancer immunotherapy. Nanocomplex-mediated vaccination can efficiently deliver nucleic acids encoding neoantigens to lymphoid tissues and antigen-presenting cells. Polyethylenimine (PEI) was conjugated with farnesylthiosalicylic acid (FTS) to form micelles. Subsequent interaction with nucleic acids led to formation of polymer/nucleic acid nanocomplexes of well-controlled structure. Tumor transfection via FTS-PEI was much more effective than that by PEI, other PEI derivatives, or naked DNA. Significant numbers of transfected cells were also observed in draining lymph nodes (LNs). In vivo delivery of ovalbumin (OVA; a model antigen) expression plasmid (pOVA) by FTS-PEI led to a significant growth inhibition of the OVA-expressing B16 tumor through presentation of OVA epitopes as well as other epitopes via epitope spreading. Moreover, in vivo delivery of an endogenous melanoma neoantigen tyrosinase-related protein 2 (Trp2) also led to substantial tumor growth inhibition. FTS-PEI represents a promising transfection agent for effective gene delivery to tumors and LNs to mediate effective neoantigen vaccination.

Most existing vaccines use activators that polarize the immune response to T-helper (Th) 2 response for antibody production. Our positively charged chitosan (Cs)-based nanocomplex (CNC) drives the Th1 response through unknown mechanisms. As receptors for the positively charged CNC are not determined, the physico-chemical properties are hypothesized to correlate with its immunomodulatory effects. To clarify the effects of surface charge and size on the immune response, smaller CNC and negatively charged CNC encapsulating ovalbumin are tested on dendritic cell (DC) 2.4 ​cells. The negatively charged CNC loses activity, but the smaller CNC does not. To further evaluate the material effects, we replace Cs by poly-amino acids. Compared with the negatively charged nanocomplex, the positively charged one preserves its activity. Using immature bone marrow-derived DCs (BMDC) enriched from BALB/c mice as a model to analyze DC differentiation, treatments with positively charged nanocomplexes evidently increase the proportions of Langerin+ dermal DC, CD11blo interstitial DC, and CD8a+ conventional DC. Additionally, vaccination with two doses containing positively charged nanocomplexes are safe and increase ovalbumin-specific IgG and recall T-cell responses in mice. Overall, a positive charge seems to contribute to the immunological effect of nanocomplexes on elevating the Th1 response by modulating DC differentiation.

Most organophosphates (OPs) are hydrophobic, and after exposure, can sequester into lipophilic regions within the body, such as adipose tissue, resulting in long term chronic effects. Consequently, there is an urgent need for therapeutic agents that can decontaminate OPs in these hydrophobic regions. Accordingly, an enzyme-polymer surfactant nanocomplex is designed and tested comprising chemically supercharged phosphotriesterase (Agrobacterium radiobacter; arPTE) electrostatically conjugated to amphiphilic polymer surfactant chains ([cat.arPTE][S - ]). Experimentally-derived structural data are combined with molecular dynamics (MD) simulations to provide atomic level detail on conformational ensembles of the nanocomplex using dielectric constants relevant to aqueous and lipidic microenvironments. These show the formation of a compact admicelle pseudophase surfactant corona under aqueous conditions, which reconfigures to yield an extended conformation at a low dielectric constant, providing insight into the mechanism underpinning cell membrane binding. Significantly, it demonstrated that [cat.arPTE][S - ] spontaneously binds to human mesenchymal stem cell membranes (hMSCs), resulting in on-cell OP hydrolysis. Moreover, the nanoconstruct can endocytose and partition into the intracellular fatty vacuoles of adipocytes and hydrolyze sequestered OP., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Developing cost-effective, energy-saving, and eco-friendly methods to construct nanopesticides fulfill the requirement of modern agriculture. Benefiting from the versatility of metal-based complexes, a facile copper-driven method is discovered for the formation of a fungicide prothioconazole nanocomplex (Cu-Pro) with the particle size of ≈300 ± 85 nm. Interestingly, adding 0.5-1% of anionic surfactants could generate nanocomplexes within 60 ± 12 nm and form stable dispersed nanosuspensions. Both nanocomplexes exhibit remarkable control efficacy against six plant pathogenic fungi, and the EC 50 values are 1.4-4.8 times lower than that of prothioconazole technical concentrate (Pro TC). In addition, the novel nanocomplexes demonstrate better resistance against UV irradiation and the half-lives are 3.27- and 1.56-times longer than that of Pro TC, respectively. The acute toxicity of prothioconazole nanocomplexes against non-target organism zebrafish is decreased. Due to the small size and chelation with metals, the uptake and accumulation of prothioconazole in wheat plant is promoted, and the metabolites prothioconazole-desthio is significantly decreased by 42-48% than that of Pro TC. This metal coordination-based strategy seeks to open a new avenue for the high-throughput preparation of nanopesticides, providing an innovative toolbox for reducing the input of agrochemicals in sustainable plant protection., (© 2024 Wiley‐VCH GmbH.)

Background. Previously, the antitumor activity of nanocomplexes (NCs) containing nanoparticles of rare earth metal orthovanadates GdYEuVO4 and cholesterol has been approved when applied in 9:1 ratio (the cells-to-NCs), which can be considered as a conditionally therapeutic dose. Therefore, studying the potential risks of NCs exposure in terms of functional activity of hematopoietic progenitor cells is relevant. Рurpose – determining a toxic effect of NCs on functional activity of hematopoietic cells of bone marrow (BM). Materials and Methods. The study was performed in BM cells of CBA/H mice. Nanocomplexes were synthesized at Institute for Scintillation Materials of the National Academy of Sciences of Ukraine. BM cells with NCs were incubated in the ratios as follows: 9BM:1NCs; 1BM:1NCs; 1BM:9NCs, followed by assessing the number of apoptotic/necrotic cells in BM using FITC Annexin V Apoptosis Detection Kit I (BD, USA) by means of “FACS Calibur” flow cytometer (“BD”, USA). Hematopoietic progenitor cells of BM were functionally evaluated in vivo by determining the content of colony-forming units of the spleen (CFUs) and the number of myelokaryocytes in lethally irradiated recipients on day 8 after administering BM cells, pre-incubated with NCs. Survival of irradiated recipient mice after BM administration was recorded 12 days long. Results and discussion. The dose-dependent effect of functional potential in- hibition for BM hematopoietic progenitor cells under NCs influence has been established. Although, in vitro processing the BM cells with a conditionally therapeutic dose of NCs (9BM:1NCs) before administration to irradiated animal caused remodeling of cell membranes and contributed to apoptotic manifes- tations, but it did not lead to strong changes in their colony-forming potential and did not reduce the number of BM cells in animals if compared with the introduced BM cells without NCs treatment. Increasing the NCs concentration five- and tenfold significantly reduced the colony-forming potential of BM cells, caused BM hypoplasia and a crucial reduction in the survival of recipient animals, indicating possible toxic effects of this compound when administered at high concentrations. Conclusions. The toxic effect of NCs is detected only when certain concen- trations, significantly exceeding the conditionally therapeutic dose previously determined when treating the experimental oncology diseases, are used.

• Crystal structure of new octa-coordinated carbacylamidophosphate-la (III) complex C1. • Sonochemical synthesis of nano/micro structures of Carbacylamidophosphate-based la (III) complexes C'1 - C'3. • Study of bonding modes in the synthesized complexes via DFT. • Quantitative analyses of intermolecular interactions in the crystalline structures by hirshfeld and NCI analyses. • In vitro evaluation of antibacterial property of the synthesized compounds. The present study tries to contribute to the body of knowledge concerning the effects of O-donor ligands based on carbacylamidophosphate on the topology, geometry, and dimensions of relevant metal complexes. Accordingly, the octa-coordinated lanthanum (III) complex with formula, [La(L1) 4 Cl 2 ]Cl (C1) (L1 = 4-NC 5 H 4 C(O)NHP(O)(NC 6 H 12) 2), has been synthesized and its crystal structure has been determined. In the crystal structure, C1 is C 2 -symmetrical, and there are separate [La(L1) 4 Cl 2 ]+ cations and Cl- anions. In the complex molecule, the four L1 ligands adopt two anti - and two syn -chelating conformations. Moreover, two other carbacylamidophosphate-based lanthanide complexes La(L2) 2 (NO 3) 3 (C2) (L2 = PhC(O)NHP(O)(NH(tert ‑C 4 H 9)) 2) 2 (NO 3) and La(L3) 2 (NO 3) 3 (H 2 O)[(CH 3) 2 CO] (C3) (L3 = (4-NO 2 C 6 H 4 CONHPO(NC 4 H 8 O) 2) were considered and density functional theory computations, at the B3PW91 level, were performed to gain a deeper understanding of the structural and electronic properties in complexes (C1 - C3). Nano and micro-structures of (C'1 - C' 3) were prepared by means of a sonochemical process to study how the reaction condition and non-covalent forces function in terms of the form as well as the size of the particles in these complexes. Thermal gravimetric analysis (TGA) and differential thermal analysis (DTA) were performed on compounds C'1- C' 3. The Hirshfeld surface analysis and NCI method were used to show the effects of non-covalent interactions on the compounds' morphologies. The antimicrobial activity of all selected compounds has been screened against two Gram-positive (Bacillus subtilis, Staphylococcus aureus) and one Gram-negative (Escherichia coli) bacteria by well diffusion method. The results indicated that all selected compounds did not show any antibacterial activity against bacteria as compared to standard drugs. [Display omitted] New octa-coordinated lanthanum (III) complex, [La(L1) 4 Cl 2 ]Cl, containing a carbacylamidophosphate ligand (L1) has been synthesized at bulk form and nano-scale. Crystal structure is observed in a butterfly geometry and nanostructures are determined in a rod-like morphology. To gain a deeper understanding of the adopted bonding modes and role of non-covalent interactions in CAPh-La (III) complexes, two other carbacylamidophosphate-based lanthanide complexes were considered, and their micro/nano-structures were prepared, as well as theoretical calculation have been executed. The antimicrobial activity of all selected compounds has been screened against some bacteria strains. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the organic solvent-free method has considerable potential for delivery systems in food applications. In this study, Nanocomplex of zein and pectin from apple (AP) or citrus (CP) was systemically fabricated and characterized by adjusting pectin pH (2.0–11.0) and mass ratios of zein:pectin (1:0, 1:0.5, 1:1, 1:2 and 1:3) via one-step pH-shifted process. Results showed that the size of zein/pectin nanocomplex remarkably decreased from >500 nm to ∼150 nm with the increasing pH level of pectin solution and proportion of pectin addition. Spherical shape was observed for nanocomplex formed by AP and CP in transmission electron microscopy images. Compared with zein/AP nanocomplex , zein/CP nanocomplex exhibited the smaller size, smoother surface and lower surface hydrophobicity, prompting us to conclude that CP, as compared to AP, had better performance. To further explore the mechanism, the behavior difference could be interpreted by the altered hydrophobic interaction between zein and pectin as revealed by fluorescence spectroscopy and Fourier transform infrared spectroscopy (FTIR). Findings in this study would facilitate the understanding of interaction between zein and pectin and provide new perspectives of pH-shift induced zein nanocomplex. • Zein/pectin nanocomplex was fabricated by an organic solvent free method. • Physiochemical properties of nanocomplex were tunable by pectin's source and pH. • Nanocomplex by pectin from apple (AP) and citrus (CP) showed different properties. • Nanocomplex by CP showed better encapsulation performance than that by AP. • CP compared to AP could interact with zein via stronger hydrophobic interaction. [ABSTRACT FROM AUTHOR]

Acute toxicity of noncovalent nanocomplex of C60 fullerene with Cisplatin (Cis-Pt) (the ratio of compounds C60:Cis-Pt by weight 1:1) in a dose progression (7.5 + 7.5, 15.0 + 15.0, 22.5 + 22.5, 30.0 + 30.0, 37.5 + 37.5, and 45.0 + 45.0 mg/kg) was investigated in mice of BALB/c line. Mice were injected with C60–Cis-Pt nanocomplex or free Cis-Pt at the same doses single intraperitoneally and observed for 14 days. A comparative study of the toxicity of free Cis-Pt and Cis-Pt at noncovalent complexation with C60 fullerene (C60–Cis-Pt nanocomplex) demonstrated halving the toxicity of C60–Cis-Pt nanocomplex in comparison with free Cis-Pt: LD50 (Cis-Pt) 15.6 ± 1.3 mg/kg vs LD50 (C60–Cis-Pt) 36.1 ± 2.8 mg/kg. The toxic effects of C60–Cis-Pt nanocomplex and free Cis-Pt were detected at doses 22.5 + 22.5 mg/kg and 15.0 mg/kg, respectively, and were accompanied by impaired mice behavior, decreased body weight and animal survival, hematotoxicity, and pathological changes in heart, liver, spleen, and kidneys. It was shown that C60 fullerene complexed with Cis-Pt prevented drug-induced decrease in animal survival, anemia, thrombocytosis, and leukopenia development, as well as inflammatory processes in spleen, heart, kidney, and liver. The obtained results indicate the prospects for using noncovalent nanocomplex C60–Cis-Pt in antitumor therapy at low therapeutic doses of Cis-Pt. [ABSTRACT FROM AUTHOR]

Abstract Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

“Thamira parpam” (TP), a copper-based herbometallic oxide (copper (II) oxide) nanodrug has been used in Siddha medicine for centuries because of its anti-ulcerogenic property. However, the physicochemical properties and in vivo toxicity of TP still remain elusive. Rigorous clinical translation requires deciphering these vital properties. We have synthesized TP following a gold standard protocol in the traditional Siddha methodology. We assessed the size, phase, elemental constituents, and thermal stability of TP by SEM and TEM, XRD, EPR, and EDAX analyses, respectively. The results depicted the conversion of metallic copper into copper (II) oxide in the final stages of TP preparation and exhibited nanodimensions ranging between 10 and 50 nm. The XPS spectra revealed the presence of oxygen-deficient state and a carbonaceous coating was found on the surface of TP using TEM analysis. In vivo safety was studied in rat toxicity models by adopting OECD guidelines. Body weight changes, feed, and water intake were unaltered upon TP administration. Hematological, biochemical profiling, and histopathological findings also suggested its nontoxic nature with no abnormalities in major organs and its functions. Interestingly, we found that the metal toxicity could have been subdued because of the carbonaceous coating around the nanoparticle copper (II) oxide, confirming that the drug is safe at a low dose. Overall, our study has enlightened the safety of TP supporting the use of Siddha formulations.

As one of the gene therapies, RNA interference (RNAi) effectively suppresses only specific genes, targeting various diseases in which they are involved. For the successful process of RNAi, efficient and safe delivery of small RNAs, including small interfering RNA and short hairpin RNA, is essential. Herein, an S‐R11 fusion peptide, SPACE peptide conjugated with poly‐arginine, was introduced to deliver small RNAs into immune cells that are difficult to transfect. This S‐R11 peptide stably formed a spontaneous self‐assembling nanocomplex through electrostatic attraction and hydrogen bonding with small RNAs. The nanocomplex showed about 5.3‐fold better permeation efficiency than the conventional Lipofectamine™ 2000 for RAW 264.7 macrophage cells. Moreover, it induced about 66.2% silencing effect of the target gene in the cells activated with polyinosinic:polycytidylic acid (poly (I:C)). In addition, the cell viability of fusion peptide was ensured even in a concentration range exceeding the concentration used in the nanocomplex. Based on these results, it is expected that the nanocomplex in this study can be used as a new gene delivery system that can overcome the challenge of gene therapies to immune cells. [ABSTRACT FROM AUTHOR]

Maryam Hafizi,1 Somayeh Kalanaky,1 Saideh Fakharzadeh,1 Ehsan Janzamin,2 Tarlan Arjmandi,1 Amir Atashi,3,* Mohammad Hassan Nazaran1,* 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2Flowcyt Science-Based Company, Tehran, Iran; 3Stem Cell and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran*These authors contributed equally to this workCorrespondence: Amir Atashi; Mohammad Hassan Nazaran Tel/Fax +98 23 3239 45000; +98 21 8899 2123Email atashia@shmu.ac.ir; mnazaran@nanochelatingtechnology.comBackground: Nowadays, smart synthesized nanostructures have attracted wide attention in the field of stem cell nanotechnology due to their effect on different properties of stem cells.Methods: GFc7 growth nanofactor was synthesized based on nanochelating technology as an iron-containing copper chelator nanocomplex. The effect of this nanocomplex on the expansion and differentiation of hematopoietic stem cells (HSCs) as well as its performance as a cryoprotectant was evaluated in the present study.Results: The results showed that the absolute count of CD34+ and CD34+CD38− cells on days 4, 7, 10 and 13; the percentage of lactate dehydrogenase enzyme on the same days and CD34+CXCR4 population on day 10 were significantly increased when they were treated with GFc7 growth nanofactor in a fetal bovine serum (FBS)-free medium. This medium also led to delayed differentiation in HSCs. One noticeable result was that CD34+CD38− cells cultured in an FBS medium were immediately differentiated into CD34+CD38+ cells, while CD34+CD38− cells treated with GFc7 growth nanofactor in FBS medium did not show such an immediate significant differentiation. De-freezing GFc7-treated CD34+ cells, which were already frozen according to cord blood bank protocols, showed a higher percentage of cell viability and a larger number of colonies according to colony-forming cell assay as compared to control.Conclusion: It can be claimed that treating HSCs with GFc7 growth nanofactor leads to quality and quantity improvement of HSCs, both in terms of expansion in vitro and freezing and de-freezing processes.Keywords: expansion, GFc7, human hematopoietic stem cells, nanocomplex, nanochelating technology

The aim of this study was to evaluate the toxicity of noncovalent nanocomplex of C60 fullerene with cisplatin (C60-Cis-Pt) against normal cells. The toxicity of the C60-Cis-Pt nanocomplex compared to the free Cis-Pt was studied by estimating kidney human embryonic (HEK293) cells viability using MTT assay and rat erythrocytes resistance to acid haemolysis. It was shown that free 40 μM Cis-Pt changed the morphology and reduced the viability of HEK293 cells, as well as increased the number of haemolyzed erythrocytes compared to the control. According to the investigated parameters analysis no cytotoxic effects of C60-Cis-Pt nanocomplex was observed at Cis-Pt equivalent concentration. The prevention of Cis-Pt toxic action against normal cells by its complexation with C60 fullerene opens the prospect of nanostructure usage as an effective cytoprotector and a target carrier in tumor cells.

Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) in the liver due to chronic injuries and inflammation. These injuries activate and transform quiescent hepatic stellate cells (HSCs) into proliferative myofibroblast-like cells, which are the key contributors to the secretin of ECM in the fibrotic liver. The insulin-like growth factor 2 receptor (IGF2R) is a multifunctional receptor that is overexpressed on activated HSCs and is a specific molecular marker of activated HSCs in the fibrotic liver. We recently discovered an IGF2R-specific peptide that significantly increases the binding affinity and uptake of a protein-based siRNA nanocomplex to activated HSCs. However, there is a potential concern about the immunogenicity of protein-based siRNA delivery systems. In this study, we used the IGF2R-specific peptide to modify a small peptide-based siRNA nanocomplex for HSC-specific drug delivery. We incorporated a short spacer and glutamate residues into the IGF2R peptides. The siRNA nanocomplex modified with the IGF2R-3GK6E peptide demonstrated higher HSC specificity compared to an unmodified nanocomplex. This peptide-based nanocomplex provides a promising platform to effectively deliver Pcbp2 siRNA to activated HSCs for the treatment of liver fibrosis.

Alzheimer's disease (AD) poses a significant burden on the economy and healthcare systems worldwide. Although the pathophysiology of AD remains debatable, its progression is strongly correlated with the accumulation of tau aggregates. Therefore, tau clearance from brain lesions can be a promising strategy for AD therapy. To achieve this, the present study combined proteolysis-targeting chimera (PROTAC), a novel protein-degradation technique that mediates degradation of target proteins via the ubiquitin-proteasome system, and a neurotransmitter-derived lipidoid (NT-lipidoid) nanoparticle delivery system with high blood-brain barrier-penetration activity, to generate a novel nanomedicine named NPD. Peptide 1, a cationic tau-targeting PROTAC is loaded onto the positively charged nanoparticles using DNA-intercalation technology. The resulting nanomedicine displayed good encapsulation efficiency, serum stability, drug release profile, and blood-brain barrier-penetration capability. Furthermore, NPD potently induced tau clearance in both cultured neuronal cells and the brains of AD mice. Moreover, intravenous injection of NPD led to a significant improvement in the cognitive function of the AD mice, without any remarkable abnormalities, thereby supporting its clinical development. Collectively, the novel nanomedicine developed in this study may serve as an innovative strategy for AD therapy, since it effectively and specifically induces tau protein clearance in brain lesions, which in turn enhances cognition., (© 2024 Wiley‐VCH GmbH.)

Gene therapy can be a promising therapeutic approach to cure the fundamental causes of incurable genetic diseases. Because virus carriers are costly and can cause inflammation and immunogenicity, efficient non-viral carriers need to be developed for broader gene therapy applications. Therefore, we designed novel synergistic nanocomplexes for efficient transfection incorporated by the fusion of nuclear localization signal and cell-penetrating peptides with calcium phosphate. Fusion peptides were able to package large plasmid DNAs into nanocomplexes spontaneously and efficiently. After optimization, S-R/CaP or S-S/CaP nanocomplexes significantly improved specific luciferase expression up to 2-fold compared to Lipofectamine® 2000. In addition, the large Cas9-encoding plasmids were transfected into HEK293T cells more efficiently than Lipofectamine® 2000. Furthermore, subcutaneously injected cells to mice maintained more stable protein expression until 10 days than Lipofectamine® 2000. Moreover, the biocompatibility was revealed by observing negligible cytotoxicity, histological difference, and inflammatory cytokine release. Consequently, the new chimeric strategy will be an efficient and safe gene carrier into cells and tissues to treat various genetic diseases through gene therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Copper (II) theophylline [Cu(THP)2(H2O)4] complex in nanoscale has synthesized by ultrasonic sonication method. This method was used in the development of smaller, dispersed, and unaggregated nanoparticles (NPs). The structure of nanocomplex was described and suggested by the molar conductance, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UVVis), solubility, atomic fire absorption, and C.H.N. elemental analysis as octahedral geometry. The size and morphology of nanocomplex measured by transmission electron microscopy (TEM) were 20 nm. The nanocomplex was studied on phosphodiesterase enzyme activity in human serum of Iraqi patient›s asthma disease. The results showed a highly significant (p < 0.01) increase in the serum levels of phosphodiesterase enzyme activity in asthma patients (mean = 14.939 ± 3.021 ng/mL) compared with a control group (mean = 9.974 ± 2.032 ng/mL). The result also showed a highly significant (p < 0.01) decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with theophylline (mean = 11.253 ± 2.479 ng/mL) compared to serum patients without nano and control groups. It is vital that the result showed a highly significant (p < 0.01) decrease in the serum levels of phosphodiesterase activity in patients of asthma disease with copper nano complex (mean = 9.563 ± 2.082 ng/mL) compared in patients of asthma disease with and without theophylline. As for comparing asthma disease with copper nano complex and control group, the result showed there was no significant effect (p > 0.05). [ABSTRACT FROM AUTHOR]

The selective cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) to cancer cells but not to normal cells makes it an attractive candidate for cancer therapeutics. However, the disadvantages of TRAIL such as physicochemical instability and short half-life limit its further clinical applications. In this study, TRAIL was encapsulated into a novel anti-angiogenic nanocomplex for both improved drug distribution at the tumor site and enhanced anti-tumor efficacy. A nanocomplex was prepared firstly by entrapping TRAIL into PEG-low molecular weight heparin-taurocholate conjugate (LHT7), which is previously known as a potent angiogenesis inhibitor. Then, protamine was added to make a stable form of nanocomplex (PEG-LHT7/TRAIL/Protamine) by exerting electrostatic interactions. We found that entrapping TRAIL into the nanocomplex significantly improved both pharmacokinetic properties and tumor accumulation rate without affecting the tumor selective cytotoxicity of TRAIL. Furthermore, the anti-tumor efficacy of nanocomplex was highly augmented (73.77±4.86%) compared to treating with only TRAIL (18.49 ± 19.75%), PEG-LHT7/Protamine (47.84 ± 14.20%) and co-injection of TRAIL and PEG-LHT7/Protamine (56.26 ± 9.98%). Histological analysis revealed that treatment with the nanocomplex showed both anti-angiogenic efficacy and homogenously induced cancer cell apoptosis, which suggests that accumulated TRAIL and LHT7 in tumor tissue exerted their anti-tumor effects synergistically. Based on this study, we suggest that PEG-LHT7/Protamine complex is an effective nanocarrier of TRAIL for enhancing drug distribution as well as improving anti-tumor efficacy by exploiting the synergistic mechanism of anti-angiogenesis. [Display omitted] [ABSTRACT FROM AUTHOR]

In cancer, the use of microbots based on anaerobic bacteria as specific transporters targeting tumor tissues has been explored since most solid tumors exhibit hypoxic regions. The aim of this study was to develop and characterize magnetic microbots based on Bifidobacteria and iron oxide fluorescent magnetic nanoparticles complexed with chitosan and a hypoxia inducible plasmid. In addition, the efficiency of the microbots for gene delivery to solid tumors was evaluated in an in vivo model by florescence and luminescence. To elaborate microbots, iron oxide fluorescent magnetic nanoparticles complexed with chitosan and a hypoxia-inducible plasmid called nanocomplex (NCs) with a size of 302 nm and a ζ potential of +16 mV were obtained and loaded onto Bifidobacteria membranes. Microbots with a diameter between 1–2 µm were characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Microbots were injected intravenously through the tail vein to tumor-bearing mice, and then a magnet was placed to focus them to the tumor area. Forty-eight hours after injection, the biodistribution was determined by florescence and luminescence. The greatest luminescence and fluorescence emitted were found in tumor tissue compared with the normal organs. We created a vector that can be directed by a magnet and deliver genes whose expression is regulated by hypoxic microenvironment of tumor. [ABSTRACT FROM AUTHOR]

We herein report the synthesis of nanostructured cyclopalladated complex and its nanosilver composite for the first time. The reaction between Schiff base ligand 4-methyl-N-(3,4-dimethoxybenzylidene)] benzenamine (L) and palladium acetate gave the cyclopalladted complex (Pd1) in nanoscale. Thermal treatment of silver oxalate with Pd1 resulted in the formation of novel nanostructured composite, silver nanoparticle-decorated palladacycle (Pd2). The synthesized compounds were characterized using spectroscopic analysis (FT-IR and 1H NMR), thermal analysis (TGA), XRD and morphological analysis (SEM and TEM). The spectral analysis revealed that complex Pd1 has dimeric structure bridged with acetate ligands between two monomers. SEM images exhibited that Ag-NPs loaded on complex surface in decorated form. TEM photographs showed the particle sizes of composite ≈ 29 nm. Quantum chemical analysis of ligand and complex Pd1 has been carried out by DFT/B3LYP method. There are two suggested isomers for cyclopalladated complex named Pd1 and Pd1* which are theoretically studied and correlated with practical results. HOMO, LUMO energy values, chemical hardness–softness, electronegativity and electrophilic index were calculated. The theoretical data obtained have been confirmed that the Pd1 isomer is more stable than Pd1* isomer which correlated well with practical results. The ligand and complexes screened for antimicrobial activity against five medically important microorganisms, namely Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. The results showed that complex Pd2 displayed the highest activity against the tested microorganisms. [ABSTRACT FROM AUTHOR]