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Samireh Badrigilan,1,* Fatemeh Heydarpanahi,2,* Jalal Choupani,3,4 Mehdi Jaymand,5 Hadi Samadian,5 Mojtaba Hoseini-Ghahfarokhi,1,5 Thomas J Webster,6 Lobat Tayebi7 1Department of Radiology and Nuclear Medicine, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; 3Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; 4Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 5Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 6Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 7Marquette University School of Dentistry, Milwaukee, WI 53233, USA*These authors contributed equally to this workCorrespondence: Mojtaba Hoseini-Ghahfarokhi; Lobat Tayebi Email m.hoseini@kums.ac.ir; lobat.tayebi@marquette.eduAbstract: Here, bismuth-based nanomaterials (Bi-based NMs) are introduced as promising theranostic agents to enhance image contrast as well as for the therapeutic gain for numerous diseases. However, understanding the interaction of such novel developed nanoparticles (NPs) within a biological environment is a requisite for the translation of any promising agent from the lab bench to the clinic. This interaction delineates the fate of NPs after circulation in the body. In an ideal setting, a nano-based therapeutic agent should be eliminated via the renal clearance pathway, meanwhile it should have specific targeting to a diseased organ to reach an effective dose and also to overcome off-targeting. Due to their clearance pathway, biodistribution patterns and pharmacokinetics (PK), Bi-based NMs have been found to play a determinative role to pass clinical approval and they have been investigated extensively in vivo to date. In this review, we expansively discuss the possible toxicity induced by Bi-based NMs on cells or organs, as well as biodistribution profiles, PK and the clearance pathways in animal models. A low cytotoxicity of Bi-based NMs has been found in vitro and in vivo, and along with their long-term biodistribution and proper renal clearance in animal models, the translation of Bi-based NMs to the clinic as a useful novel theranostic agent is promising to improve numerous medical applications.Keywords: bismuth nanoparticles, biocompatibility, pharmacokinetic, biodistribution and clearance

Hossein Derakhshankhah, 1, 2,* Samira Jafari, 1, 2,* Sajad Sarvari, 3 Ebrahim Barzegari, 4 Faezeh Moakedi, 5 Milad Ghorbani, 6 Behrang Shiri Varnamkhasti, 1 Mehdi Jaymand, 7 Zhila Izadi, 1, 8 Lobat Tayebi 9 1Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Zistmavad Pharmed Co., Tehran, Iran; 3Department of Pharmaceutical and Pharmacological Science, School of Medicine, West Virginia University, Morgantown, WV, USA; 4Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 5Department of Biochemistry and Molecular Biology, School of Medicine, West Virginia University, Morgantown, WV, USA; 6Department of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 7Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 8Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 9Marquette University School of Dentistry, Milwaukee, WI 53201, USA*These authors contributed equally to this workCorrespondence: Zhila Izadi; Lobat Tayebi Email izadi_zh@razi.tums.ac.ir; lobat.tayebi@marquette.eduAbstract: The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles’ interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.Keywords: zeolite, mesoporous, nanostructure, biosafety, biomedical applications

Rana Jahanban-Esfahlan,1,2 Khaled Seidi,3 Ali Jahanban-Esfahlan,4 Mehdi Jaymand,5 Effat Alizadeh,1 Hasan Majdi,6 Reza Najjar,7 Tahereh Javaheri,8 Peyman Zare9 1Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz 9841, Iran; 2Student Research Committee, Tabriz University of Medical Sciences, Tabriz 9841, Iran; 3Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 9841, Iran; 4Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz 9841, Iran; 5Nano Drug Delivery Research Center (NDDRC), Kermanshah University of Medical Sciences, Kermanshah 9883, Iran; 6Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 9841, Iran; 7Polymer Research Laboratory, Faculty of Chemistry, University of Tabriz, Tabriz 9841, Iran; 8Ludwig Boltzmann Institute for Cancer Research, Vienna 1090, Austria; 9Faculty of Medicine, Cardinal Stefan Wyszyński University in Warsaw, Warsaw 01-938, PolandCorrespondence: Tahereh JavaheriLudwig Boltzmann Institute for Cancer Research, Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna, AustriaTel +43-1-25077 563Fax +43-1-40160 931300Email zohre.javaheri@gmail.comPeyman ZareFaculty of Medicine, Cardinal Stefan Wyszyński University in Warsaw, Warsaw 01-938, PolandTel +48884842847Email Peymanzare33@gmail.comAbstract: Among the various nano/biomaterials used in cancer treatment, the beauty and benefits of DNA nanocomposites are outstanding. The specificity and programmability of the base pairing of DNA strands, together with their ability to conjugate with different types of functionalities have realized unsurpassed potential for the production of two- and three-dimensional nano-sized structures in any shape, size, surface chemistry and functionality. This review aims to provide an insight into the diversity of static DNA nanodevices, including DNA origami, DNA polyhedra, DNA origami arrays and bioreactors, DNA nanoswitch, DNA nanoflower, hydrogel and dendrimer as young but promising platforms for cancer theranostics. The utility and potential of the individual formats in biomedical science and especially in cancer therapy will be discussed.Keywords: static DNA nanostructures, cancer treatment, biosensing

Purpose: We report on the design of hypoxia-induced dual-stage acting dendrimeric nanoparticles (NPs) for selective delivery of two chemotherapeutic model drugs doxorubicin (DOX) and tirapazamin (TPZ) for deepened drug delivery into hypoxic tumors in vitro ., Methods: PAMAM G5 dendrimers were crosslinked with a hypoxic azo linker, attached to a mPEG to form a detachable corona on the dendrimer surface (PAP NPs). NPs were characterized by Zeta sizer, transmission electron microscope (TEM), Fourier transforms infrared (FTIR) and drug release kinetics. The anti-cancer performance of PAPs was evaluated by numerous tests in 2D and 3D cultured MDA-MB-231 breast cancer cells., Results: MTT assay showed a significant difference between PAP and PAMAMG5 in terms of biocompatibility, and the effect of PAP@DOX was significantly greater than free DOX in hypoxic conditions. The results of DAPI and Annexin V-FITC/PI cell staining also confirmed uniform drug penetration as validated by induction of 90% cell apoptosis in spheroids and a high level of PAP@DOX-induced ROS generation under hypoxia conditions. Mechanistically, PAP@DOX significantly reduced the expression of mTOR, and Notch1, while the expression of Bax and Caspase3 was considerably unregulated, compared to the controls. Importantly, hypoxia-responsive disintegration and hypoxia-induced activation of HAP drug were synergized to promote deep and homogenous HAP distribution in whole microtumor regions to efficiently eliminate residual tumor cells., Conclusion: Our results indicate the safety and high therapeutic potential of PAP system for targeted drug delivery of chemotherapeutics in particular HAPs which show maximum anti-cancer activity against hypoxic solid tumors., Competing Interests: None to declare., (©2024 The Author (s).)

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe 3 O 4 ) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe 3+ ) to ferrous (Fe 2+ ) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75-1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments., (© 2024. The Author(s).)

This study reports on the design and synthesis of hypoxia responsive nanoparticles (HRNPs) composed of methoxy polyethylene glycol-4,4 dicarboxylic azolinker-chitosan (mPEG-Azo-chitosan) as ideal drug delivery platform for Fingolimod (FTY720, F) delivery to achieve selective and highly enhanced TNBC therapy in vivo. Herein, HRNPs with an average size of 49.86 nm and a zeta potential of +3.22 mV were synthetized, which after PEG shedding can shift into a more positively-charged NPs (+30.3 mV), possessing self-activation ability under hypoxia situation in vitro, 2D and 3D culture. Treatment with lower doses of HRNPs@F significantly reduced MDA-MB-231 microtumor size to 15 %, induced apoptosis by 88 % within 72 h and reduced highly-proliferative 4 T1 tumor weight by 87.66 % vs. ∼30 % for Fingolimod compared to the untreated controls. To the best of our knowledge, this is the first record for development of hypoxia-responsive chitosan-based NPs with desirable physicochemical properties, and selective self-activation potential to generate highly-charged nanosized tumor-penetrating chitosan NPs. This formulation is capable of localized delivery of Fingolimod to the tumor core, minimizing its side effects while boosting its anti-tumor potential for eradication of TNBC solid tumors., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A novel thermal-responsive β-cyclodextrin-based magnetic hydrogel [β-cyclodextrin- graft -poly( N -isopropylacrylamide)/Fe 3 O 4 (β-CD- g -PNIPAAm/Fe 3 O 4 )] was fabricated as a novel nanomedicine for chemo/hyperthermia treatment of cancer cells. Firstly, β-CD was modified by maleic anhydride (MA) followed by copolymerization with NIPAAm monomer and thiol-end capped Fe 3 O 4 nanoparticles (NPs) in the presence of a crosslinker through acrylamide-thiol polymerization system to afford a magnetic hydrogel. The saturation magnetization ( δ s ) value for developed hydrogel was determined to be 8.2 emu g -1 . The hydrogel was physically loaded with an anticancer agent, doxorubicin hydrochloride (Dox). The encapsulation efficiency (EE) of drug into the hydrogel was obtained as 73 %. The system represented acceptable thermal-triggered drug release behavior that best fitted with Higuchi model, demonstrating the release of drug is mostly controlled by diffusion mechanism. The anticancer performance of the β-CD- g -PNIPAAm/Fe 3 O 4 -Dox was evaluated using MCF7 cells by MTT-assay. In addition, flow cytometry analyses showed considerable cellular uptake of Dox in the cells treated with β-CD- g -PNIPAAm/Fe 3 O 4 -Dox (∼70 %) compared to free Dox (∼28 %). As results, in time period of 48 h by combination of chemo- and hyperthermia-therapies, the developed system displayed greater anticancer efficiency than the free Dox., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers., (© 2024. The Author(s).)

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33's protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients., (© 2024. The Author(s).)

The creation of a suitable scaffold is a crucial step in the process of bone tissue engineering (BTE). The scaffold, acting as an artificial extracellular matrix, plays a significant role in determining the fate of cells by affecting their proliferation and differentiation in BTE. Therefore, careful consideration should be given to the fabrication approach and materials used for scaffold preparation. Natural polypeptides such as gelatin and collagen have been widely used for this purpose. The unique properties of nanoparticles, which vary depending on their size, charge, and physicochemical properties, have demonstrated potential in solving various challenges encountered in BTE. Therefore, nanocomposite biomaterials consisting of polymers and nanoparticles have been extensively used for BTE. Gelatin has also been utilized in combination with other nanomaterials to apply for this purpose. Composites of gelatin with various types of nanoparticles are particularly promising for creating scaffolds with superior biological and physicochemical properties. This review explores the use of nanocomposite biomaterials based on gelatin and various types of nanoparticles together for applications in bone tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A novel strategy was designed and developed based of horseradish peroxidase (HRP)-mediated crosslinking of tyramine-functionalized starch (Tyr-St), tannic acid (TA) and phenolated-magnetic nanoparticles (Fe 3 O 4 -PhOH NPs), and simultaneous loading of doxorubicin hydrochloride (Dox) to afford a pH-responsive magnetic hydrogel-based drug delivery system (DDS) for synergistic in vitro chemo/hyperthermia therapy of human breast cancer (MCF-7) cells. The developed St-g-PTA/Fe 3 O 4 magnetic hydrogel showed porous micro-structure with saturation magnetization (δ s ) value of 19.2 emu g -1 for Fe 3 O 4 NPs content of ∼7.4 wt%. The pore sizes of the St-g-PTA/Fe 3 O 4 hydrogel was calculated to be 2400 ± 200 nm -2 . In vitro drug release experiments exhibited the developed DDS has pH-dependent drug release behavior, while at physiological pH (7.4) released only 30 % of the loaded drug after 100 h. Human serum albumin (HSA) adsorption capacities of the synthesized St/Fe 3 O 4 and St-g-PTA/Fe 3 O 4 magnetic hydrogels were obtained as 86 ± 2.2 and 77 ± 1.9 μgmg -1 , respectively. The well-known MTT-assay approved the cytocompatibility of the developed St-g-PTA/Fe 3 O 4 hydrogel, while the Dox-loaded system exhibited higher anti-cancer activity than those of the free Dox as verified by MTT-assay, and optical as well as florescent microscopies imaging. The synergistic chemo/hyperthermia therapy effect was also verified for the developed St-g-PTA/Fe 3 O 4 -Dox via hot water approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Novel electrically conductive nanofibrous scaffolds were designed and fabricated through the grafting of aniline monomer onto a phenylamine-functionalized alginate (Alg-NH 2 ) followed by electrospinning with poly(vinyl alcohol) (PVA). Performance of the prepared scaffolds in bone tissue engineering (TE) were studied in terms of physicochemical (e.g., conductivity, electroactivity, morphology, hydrophilicity, water uptake, and mechanical) and biological (cytocompatibility, in vitro biodegradability, cells attachment and proliferation, hemolysis, and protein adsorption) properties. The contact angles of the scaffolds with water drop were obtained about 50 to 60° that confirmed their excellent hydrophilicities for TE applications. Three dimensional (3D), inter-connected and uniform porous structures of the scaffolds without any bead formation was confirmed by scanning electron microscopy (SEM). Electrical conductivities of the fabricated scaffolds were obtained as 1.5 × 10 -3 and 2.7 × 10 -3 Scm -1 . MTT assay results revealed that the scaffolds have acceptable cytocompatibilities and can enhance the cells adhesion as well as proliferation, which approved their potential for TE applications. Hemolysis rate of the developed scaffolds were quantified <2 % even at high concentration (200 μgmL -1 ) of samples that approved their hemocompatibilities. The scaffolds were also exhibited acceptable protein adsorption capacities (65 and 68 μgmg -1 ). As numerous experimental results, the developed scaffolds have acceptable potential for bone TE., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

As pivotal role of scaffold in tissue engineering (TE), the aim of present study was to design and development of extracellular matrix (ECM)-mimetic electrically conductive nanofibrous scaffolds composed of polyaniline-grafted tragacanth gum (TG-g-PANI) and poly(vinyl alcohol) (PVA) with different PANI content for skin tissue engineering (STE) application. The fabricated scaffolds were preliminary evaluated in terms of some physicochemical and biological properties. Cytocompatibility and cells proliferation properties of the scaffolds were examined with the well-known MTT assay, and it was found that the developed scaffolds have proper cytocompatibilities and can enhances the mouse fibroblast L929 cells adhesion as well as proliferation, which confirm their potential for STE applications. Hemocompatibility assay revealed that the hemolysis rate of the fabricated scaffolds were <2 % even at a relatively high concentration (200 μgmL -1 ) of samples, therefore, these scaffolds can be considered as safe. Human serum albumin (HSA) protein adsorption capacities of the fabricated scaffolds were quantified as 42 and 49 μgmg -1 that represent suitable values for a successful TE. Overall, the fabricated scaffold with 20 wt% of TG-g-PANI showed higher potential in both physicochemical and biological features than scaffold with 30 wt% of mentioned copolymer for STE application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Water pollution is increasing significantly owing to industrialization and population growth that lead to serious environmental and health issues. Therefore, the design and development of more effective wastewater treatment approaches are necessary due to a significant upsurge in demand for freshwater. More recently, metal-organic frameworks (MOFs) have attracted attention in environmental science owing to their tunable porosity, unique structure, flexibility, and various composition. Despite these attractive advantages, some drawbacks, including intrinsic fragility, unsatisfied processability, dust formation, and poor reusability, have greatly limited their applications. Therefore, MOFs are often designed as supported-based MOFs (e.g., MOFs-coated composites) or 3D structured composites, such as MOFs-based hydrogels. MOFs-based hydrogels are excellent candidates in the sorption process because of their appropriate adsorption capacity, porous structure, good mechanical properties, durability as well as biodegradable features. In this review, the removal of different pollutants (e.g., synthetic dyes, phosphates, heavy metals, antibiotics, and some organic compounds) from aqueous media has been studied by the adsorption process using MOFs-based hydrogels. The important advancements in the fabrication of MOFs-based hydrogels and their capacities in the adsorption of pollutants under experimental conditions have been discussed. Finally, problems and future perspectives on the adsorption process using MOFs-based hydrogels have been investigated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Hypoxia is a unique characteristic of the solid tumor microenvironment. Hypoxia contributes to multi-drug resistance, metastasis and cancer relapse through numerous molecular pathways, but at the same time provides an opportunity for the development of novel drugs or modalities specifically targeting hypoxic tumor regions. Given the high significance of tumor hypoxia in therapeutic results, we here discuss a variety of hypoxia-adopted strategies, and their potential and utility in the treatment of deep-seated hypoxic tumor cells. We discuss the merits and demerits of these approaches, as well as their combination with other approaches such as photodynamic therapy. We also survey the currently available 3D hypoxia modeling systems, in particular organoid-based microfluidics. Finally, we discuss the potential and the current status of preclinical tumor hypoxia approaches in clinical trials for advanced cancer. We believe that multi-modal imaging and therapeutic hypoxia adopted drug delivery platforms could provide better efficacy and safety profiles, and more importantly personalized therapy. Determining the hypoxia status of tumors could offer a second chance for the clinical translation of hypoxia-based agents, such as hypoxia activated prodrugs (HAPs) from bench to bedside., Competing Interests: Declaration of Competing Interest MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc., Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc., Minneapolis-St. Paul MN; Sunlighten, Kansas City, MO; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany; Klox Asia, Guangzhou, China. Stockholding: Niraxx Light Therapeutics, Inc., Irvine CA; JelikaLite Corp, New York NY. The other authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Chitosan and its derivatives are among biomaterials with numerous medical applications, especially in cancer. Chitosan is amenable to forming innumerable shapes such as micelles, niosomes, hydrogels, nanoparticles, and scaffolds, among others. Chitosan derivatives can also bring unprecedented potential to cross numerous biological barriers. Combined with other biomaterials, hybrid and multitasking chitosan-based systems can be realized for many applications. These include controlled drug release, targeted drug delivery, post-surgery implants (immunovaccines), theranostics, biosensing of tumor-derived circulating materials, multimodal systems, and combination therapy platforms with the potential to eliminate bulk tumors as well as lingering tumor cells to treat minimal residual disease (MRD) and recurrent cancer. We first introduce different formats, derivatives, and properties of chitosan. Next, given the barriers to therapeutic efficacy in solid tumors, we review advanced formulations of chitosan modules as efficient drug delivery systems to overcome tumor heterogeneity, multi-drug resistance, MRD, and metastasis. Finally, we discuss chitosan NPs for clinical translation and treatment of recurrent cancer and their future perspective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mahmudi, Adili-Aghdam, Shahpouri, Jaymand, Amoozgar and Jahanban-Esfahlan.)

Alginate-grafted polyaniline (Alg-g-PANI) microparticles were synthesized through the grafting of aniline onto functionalized Alg followed by double crosslinking by glutaraldehyde and calcium chloride. The performance of the developed microparticles as adsorbent in simultaneous removal of malachite green (MG) and congo red (CR) dyes were examined by the batch method. Experimental parameters, including adsorbent amount, pH, initial dyes concentrations, and contact time were optimized. Langmuir and Freundlich adsorption models were employed to explore the equilibrium isotherm. As the Langmuir model results, the maximum adsorption capacities (Q m ) of microparticles for the MG and CR dyes were obtained as 578.3 and 409.6 mgg -1 , respectively. Adsorption kinetics for both dyes were well-fitted with the pseudo-second-order model that confirm the rate-limiting step might be the chemical adsorption. The adsorbent was regenerated via desorption process and was reusable five times without a substantial decrease in its adsorption efficacy in first three cycles. Adsorbent-dyes interactions were computationally evaluated using Gromacs package, and it was found that both MG and CR are able to interact strongly with the adsorbent. In accordance with experimental results, simulation data revealed that MG can be removed more efficiently than those of the CR. As the experimental results, we could conclude that the synthesized Alg-g-PANI microparticles can be used as a nature-inspired adsorbent for simultaneous removals of CR and MG dyes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We investigated the probiotic potential of a microencapsulated Enterococcus faecium ABRIINW.N7 for control of Streptococcus agalactiae infection in hybrid ( Oreochromis niloticus × Oreochromis mossambicus ) red tilapia. A two-phase experiment approach was completed in which E. faecium bacteria were propagated, from which a culture was isolated, identified using molecular techniques, and microencapsulated to produce a stable commercial fructooligosaccharide (FOS) and fenugreek (Fk) product of optimal concentration. The FOS and Fk products were assessed in a 90-days in vivo challenge study, in which red hybrid tilapia were allocated to one of five treatments: (1) No Streptococcus agalactiae (Sa) challenge (CON); (2) Sa challenge only (CON + ); (3) Sa challenge in a free cell (Free Cell); (4) Sa challenge with 0.8% (w/v) Alginate; (5) Microencapsulated FOS and Fk. In vitro results showed high encapsulation efficiency (≥98.6 ± 0.7%) and acceptable viability of probiotic bacteria within the simulated fish digestive system and high stability of viable cells in all gel formulations (34 < SR% <63). In vivo challenges demonstrated that the FOS and Fk products could be used to control S. agalactiae infection in tilapia fish and represented a novel investigation using microencapsulation E. faecium as a probiotic diet for tilapia fish to control S. agalactiae infection and to lower fish mortality. It is recommended that local herbal gums such as 0.2% Persian gum and 0.4% Fk in combination with 0.8% alginate (Formulation 7) can be used as a suitable scaffold and an ideal matrix for the encapsulation of probiotics. These herbal gums as prebiotics are capable of promoting the growth of probiotic cells in the food environment and digestive tract., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nami, Kahieshesfandiari, Lornezhad, Kiani, Elieh-Ali-Komi, Jafari, Jaymand and Haghshenas.)

Magnetite nanoparticles (MNPs) composed of γ-Fe 2 O 3 and hydroxyapatite (HAp) were modified by hexamethylen-1,6-diisocyanate (HMDI) followed by thiourea dioxide and used as recyclable catalyst for the synthesis of some newly derivatives of chromeno[2,3-b]pyridine. The products were synthesized in excellent yields via one-pot three-component reactions of 3-cyano-6-hydroxy-4-methyl-pyridin-2(1H)-one with aldehydes and dimedone under solvent-free conditions. The successful synthesis of products were confirmed using Fourier transform infrared (FTIR), proton/carbon nuclear magnetic resonance ( 1 H/ 13 C NMR), and mass spectroscopies as well as physical data (e.g., melting points and elemental composition). The in vitro antioxidant and antifungal activities of the synthesized samples were evaluated using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and potato dextrose agar (PDA) medium, respectively. Based on results, the chromeno[2,3-b]pyridine derivatives exhibited excellent biological activities that qualified them for biomedical applications., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Starch is the second most abundant naturally-occurring polymer after cellulose that possess superior physicochemical and biological features with numerous practical applications ranging from industrial to biomedical. Despite, native starch suffer from some drawbacks, including difficult processability, low shear and thermal stability, weak mechanical properties, and tendency to easily retrograde and undergo syneresis. Therefore, modification of native starch is necessary for circumvent the above-mentioned problems and expanding application ranges. This natural polymer can be modified using chemical, physical, enzymatic, and genetic engineering strategies. Amongst, chemical approaches have received more attention owing to enhancing physicochemical and biological features that lead to higher performance than those of the other strategies. In this context, incorporation of sulfur functionality-containing groups (sulfonation and sulfation) can be considered as an efficient approach due to significant enhancement in physiochemical properties, including zeta potential (move to negative values), molecular weight, processiability (e.g., solubility and meltability), and rheology. Furthermore, this strategy can modified some biological features, such as hemocompatibility, protein sorption, biostability, adhesion and proliferation of numerous cells, antithrombogenicity, antiinflammatory, antiviral, antimicrobial, antioxidant, antifungal, anticoagulant and antifouling properties. Accordingly, this review highlight's the synthesis strategies, physiochemical and biological properties, as well as applications of sulfur functionality-modified starches in numerous practical fields., (Copyright © 2021. Published by Elsevier B.V.)

Chemotherapy is the most common treatment strategy for cancer patients. Nevertheless, limited drug delivery to cancer cells, intolerable toxicity, and multiple drug resistance are constant challenges of chemotherapy. Novel targeted drug delivery strategies by using nanoparticles have attracted much attention due to reducing side effects and increasing drug efficacy. Therefore, the most important outcome of this study is to answer the question of whether active targeted HA-based drug nanocarriers have a significant effect on improving drug delivery to cancer cells.This study aimed to systematically review studies on the use of hyaluronic acid (HA)-based nanocarriers for chemotherapy drugs. The two databases MagIran and SID from Persian databases as well as international databases PubMed, WoS, Scopus, Science Direct, Embase, as well as Google Scholar were searched for human studies and cell lines and/or xenograft mice published without time limit until 2020. Keywords used to search included Nanoparticle, chemotherapy, HA, Hyaluronic acid, traditional medicine, natural medicine, chemotherapeutic drugs, natural compound, cancer treatment, and cancer. The quality of the studies was assessed by the STROBE checklist. Finally, studies consistent with inclusion criteria and with medium- to high-quality were included in the systematic review.According to the findings of studies, active targeted HA-based drug nanocarriers showed a significant effect on improving drug delivery to cancer cells. Also, the use of lipid nanoparticles with a suitable coating of HA have been introduced as biocompatible drug carriers with high potential for targeted drug delivery to the target tissue without affecting other tissues and reducing side effects. Enhanced drug delivery, increased therapeutic efficacy, increased cytotoxicity and significant inhibition of tumor growth, as well as high potential for targeted chemotherapy are also reported to be benefits of using HA-based nanocarriers for tumors with increased expression of CD44 receptor., (© 2021. Springer Nature Switzerland AG.)

Lawsone (LWS) is a naphthoquinone-type dye with potential antitumor activity. LWS is used in cosmetics for coloring hair, skin, and nails. In this study, solid lipid nanoparticles (SLNs) containing LWS were prepared using a hot homogenization technique. Physicochemical properties of LWS-SLNs including encapsulation efficiency (EE), drug loading (DL), size, zeta potential, homogeneity, in vitro release, and kinetics of release were determined. The potential cytotoxic properties of LWS-SLNs were investigated. Comet assay was done to assess the genotoxicity of LWS-SLNs. The scanning electron microscopy (SEM) images revealed that LWS-SLNs were spherical and homogeneously dispersed. The average diameter of free SLNs and LWS-SLNs were 97 ± 1.4 and 127 ± 3.1 nm, respectively with high EE% (95.88 ± 3.29) and a DL of 22.72 ± 1.39 mg/mL of LWS-SLNs. The plain LWS could induce growth inhibition of A549 cells with IC 50 of 17.99 ± 1.11, 13.37 ± 1.22, and 9.21 ± 1.15 μg/mL after 24, 48, and 72 h, respectively, while LWS-SLNs had more cytotoxic effects after 48 h (9.81 ± 1.3 μg/mL). Comet assay represented clear fragmentation in the chromatin of the treated cells. Besides, LWS-SLNs (13.37 ± 1.22 μg/mL) induced ∼52 % apoptosis and even necrosis after 48 h. The qPCR results showed an enhanced downregulation of Bcl-2 and upregulation of Casp 9 due to the treatment of A549 cells with LSW-SLNs. In conclusion, a stable formulation of LWS-SLN was prepared with good physicochemical features and long-term biological effects that candidate it for in vivo trials., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A dual stimuli-responsive magnetic nanohydrogel was fabricated as a potent drug delivery system (DDS) for 'smart' treatment of cancer by chemo/hyperthermia approach. For this objective, Fe 3 O 4 nanoparticles (NPs) were produced via a co-precipitation approach and then modified by 3-(trimethoxysilyl) propylmethacrylate (MPS) moiety. The modified NPs were copolymerized with N , N '-(dimethylamino)ethyl methacrylate (DMAEMA), and maleic anhydride (MA) monomers by a free radical polymerization approach to afford a Fe 3 O 4 @P(DMAEMA- co -MA) core-shell NPs. Afterward, the NPs were shell crosslinked by the reaction of anhydride unites with neutralized cystamine (Cys). The fabricated pH- and reduction-responsive magnetic nanohydrogel was physically loaded with methotrexate (MTX), as an anticancer drug, and its drug loading efficiency (LE) was calculated as 64 ± 2.7%. The developed nanohydrogel/MTX exhibited proper stimuli-triggered drug release behavior that qualified it as an efficient DDS according to the abnormal micro-environment of cancerous tumors. The anticancer activity investigation using chemo/hyperthermia therapy approach by MTT-assay revealed that the nanohydrogel/MTX might show better clinical outcomes than those of the free MTX.

In the present study, probiotic potato chips containing a newly isolated probiotic Lactococcus lactis KUMS-T18 strain were produced by using a simple spraying method and then enhancing the stability, survival rate, and sensory characteristics of product during storage at 4 °C and 25 °C was examined for four months. Based on the results, Lactococcus lactis KUMS-T18 isolated from traditional Tarkhineh as a safe strain had high tolerance to low pH and high bile salt, anti-pathogenic activity, hydrophobicity, adhesion to human epithelial cells, auto- and co-aggregation, cholesterol assimilation and antibiotic susceptibility. Meanwhile, by micro-coating the probiotic cells in Tarkhineh formulations, elliptical to spherical shape (460-740 µm) probiotic drops were produced. The results revealed that potato chips produced with turmeric and plain Tarkhineh during storage at 4 °C, had excellent protection abilities for probiotic cells with about 4.52 and 3.46 log decreases in CFU/g respectively. On the other hand, probiotic potato chips, compared to non-probiotic and commercial potato chips, showed the criteria of probiotic products such as excellent quality and superior sensory characteristics. In summary, this study proved that probiotic Lactococcus lactis KUMS-T18 strain covered by Tarkhineh formulations as protective matrix has high potential to be used in the production of probiotic potato chips.

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.

In the present work, we studied the structure-activity relationship and kinetics of thermal inactivation of α-glucosidase A (AglA) in a 50 mM potassium phosphate buffer at pH 6.8 using p -nitrophenyl α-d-glucopyranoside ( p NPG) as the synthetic substrate following absorbance at 410 nm by UV-Vis spectrophotometer. The interface structure and residual activity plot were analyzed via biochemical measurements by means of conformational lock theory, as well. The thermal inactivation curves were plotted in temperature interval from 30 to 50 °C. Based on experimental and structural data we suggested intermediates during inactivation before the loss of enzyme activity. Arrhenius plot for thermal inactivation rate constant showed biphasic appearance related to before and after 45°C temperature. The contact areas between two subunits were ruptured and unlocked stepwise during dimer dissociation. Cleavage of these areas induced the dissociation of the subunits along with destruction of the active centers and subsequently the loss of activity. It seems that the contact areas interact with active centers by conformational changes involving secondary structural elements.

Herein, we present an interesting role of tungstate-decorated amphiphilic carbon quantum dots (A-CQDs/W) in the selective oxidative cleavage of alkenes to aldehydes. In this work, for the first time, we disclose an unprecedented tungstate-based oxidative system incorporating A-CQDs as a bridge to the homogeneous catalyst for selective and efficient cleavage of a wide substrate scope of alkenes into aldehydes. The A-CQDs/W were synthesized via a one-step hydrothermal synthesis approach using 1-aminopropyl-3-methyl-imidazolium chloride and stearic acid for the surface modification, following by anion-exchange to immobilize WO 4 -2 to A-CQDs. The A-CQDs/W act as a pseudohomogeneous metallic catalyst (PMC) for selective oxidative scission of alkenes under phase transfer catalysts (PTC) free condition without over oxidation to acids, using water and H 2 O 2 as a green oxidant. Thanks to the sub-nanometric size and novel engineered chemical structure, this PMC and reactants are in the same phase, besides they can be easily isolated from each other by extraction processes. The synthesized PMC exhibited excellent solubility and stability in various solvents. Interestingly, the system's high conversion efficiency was preserved even after eight catalytic cycles indicating the recyclability of the synthesized PMC. We believe that this study provides a significant and conceptually novel advance in oxidative cleavage chemistry.

Chemotherapy as the main cancer treatment method has non-specific effects and various side-effects. Accordingly, significant attempts have been conducted to enhance its efficacy through design and development of "smart" drug delivery systems (DDSs). In this context, natural gums, as a nice gift by the nature, can be exploited as stimuli-responsive DDSs for cancer treatment in part due to their renewability, availability, low cost, bioactivity, biocompatibility, low immunogenicity, biodegradability, and acceptable stability in both in vitro and in vivo conditions. However, some shortcomings (e.g., poor mechanical properties and high hydration rate) restrict their biomedical application ranges that can be circumvented through modification process (e.g., grafting of stimuli-responsive polymers or small molecules) to obtain tailored biomaterials. This review article aimed to compile the stimuli-responsive DDSs based on natural gums. In addition, different types of stimuli, the fundamental features of natural gums, as well as their chemical modification approaches are also shortly highlighted., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is one of the most disseminated diseases across the globe engaging the digestive system. Various therapeutic methods from traditional to the state-of-the-art ones have been applied in CRC patients, however, the attempts have been unfortunate to lead to a definite cure. MiRNAs are a smart group of non-coding RNAs having the capabilities of regulating and controlling coding genes. By utilizing this stock-in-trade biomolecules, not only disease's symptoms can be eliminated, there may also be a good chance for the complete cure of the disease in the near future. Herein, we provide a comprehensive review delineating the therapeutic relationship between miRNAs and CRC. To this, various clinical aspects of miRNAs which act as a tumor suppressor and/or an oncogene, their underlying cellular processes and clinical outcomes, and, in particular, their effects and expression level changes in patients treated with chemo- and radiotherapy are discussed. Finally, based on the results deducted from scientific research studies, therapeutic opportunities based on targeting/utilizing miRNAs in the preclinical as well as clinical settings are highlighted., (© 2021 The Authors.)

A new strategy for design and development of a magnetic "smart" drug delivery system (DDS) based on β-cyclodextrin (β-CD) and poly(2-ethyl-2-oxazoline) (PEtOx) was reported. For this purpose, a β-CD-(I) 7 was acetylated, and then EtOx monomer was grafted onto the acetylated β-CD-(I) 7 through cationic ring-opening polymerization followed by simultaneous crosslinking with amine-end capped Fe 3 O 4 nanoparticles (Fe 3 O 4 -NH 2 NPs) and cystamine to produce a β-CD-g-(PEtOx) 7 /Fe 3 O 4 as a reduction- and pH-responsive magnetic DDS. The developed magnetic nanohydrogel was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies, as well as its pH- and reduction-triggered drug release behaviors were investigated. The anticancer activity of the formulated β-CD-g-(PEtOx) 7 /Fe 3 O 4 -Dox was investigated against MCF7 cells. According to the results, the formulated β-CD-g-(PEtOx) 7 /Fe 3 O 4 -Dox can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis due to its high drug loading value (∼ 74 %), slow and stimuli-triggered drug release behavior, and acceptable magnetic properties., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Valvular heart disease (VHD) occurs as the result of valvular malfunction, which can greatly reduce patient's quality of life and if left untreated may lead to death. Different treatment regiments are available for management of this defect, which can be helpful in reducing the symptoms. The global commitment to reduce VHD-related mortality rates has enhanced the need for new therapeutic approaches. During the past decade, development of innovative pharmacological and surgical approaches have dramatically improved the quality of life for VHD patients, yet the search for low cost, more effective, and less invasive approaches is ongoing. The gold standard approach for VHD management is to replace or repair the injured valvular tissue with natural or synthetic biomaterials. Application of these biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of this type of heart disease. The focus of the present review is the current use of different types of biomaterials in treatment of valvular heart diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Taghizadeh, Ghavami, Derakhshankhah, Zangene, Razmi, Jaymand, Zarrintaj, Zarghami, Jaafari, Moallem Shahri, Moghaddasian, Tayebi and Izadi.)

The high prescribed dose of anticancer drugs and their resulting adverse effects on healthy tissue are significant drawbacks to conventional chemotherapy (CTP). Ideally, drugs should have the lowest possible degree of interaction with healthy cells, which would diminish any adverse effects. Therefore, an ideal scenario to bring about improvements in CTP is the use of technological strategies to ensure the efficient, specific, and selective transport and/or release of drugs to the target site. One practical and feasible solution to promote the efficiency of conventional CTP is the use of ultrasound (US). In this review, we highlight the potential role of US in combination with lipid-based carriers to achieve a targeted CTP strategy in engineered smart drug delivery systems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly( N -isopropylacrylamide- block -acrylic acid) (HS-PNIPAAm- b -PAA) onto Fe 3 O 4 @Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe 3 O 4 @Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm- b -PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe 3 O 4 @Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe 3 O 4 @Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe 3 O 4 @Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe 3 O 4 nanomaterials in its structure.

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L / )].1.3DMA (MOF-1) {L = 4, 4 / -bipyridine and L /  = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu +2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, β and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.

This study aimed to design and development of a magnetic natural hydrogel based on alginate (Alg), gelatin (Gel), and Fe 3 O 4 magnetic nanoparticles (MNPs) as an efficient and "smart" drug delivery system (DDS) for cancer therapy. First, Alg was partially oxidized (OAlg), and then the Alg-Gel chemical hydrogel was synthesized through "Shift-Base" condensation reaction. Afterward, Fe 3 O 4 NPs were incorporated into the hydrogel through in situ chemical co-precipitation approach. The scanning electron microscopy (SEM) image exhibited that the fabricated Alg-Gel hydrogel has porous microstructure without microphase separation. Transmission electron microscopy (TEM) revealed the well-defined formation of Fe 3 O 4 NPs throughout the Alg-Gel hydrogel with spherical shapes in the size range of 25 ± 10 nm. Saturation magnetization (δ s ) value of the Alg-Gel/Fe 3 O 4 was obtained to be 31 emu g -1 that represent proper magnetic property for "smart" drug delivery purposes. The obtained Alg-Gel/Fe 3 O 4 was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies as well as its anticancer activity was investigated against Hela cells. The formulated Alg-Gel/Fe 3 O 4 -Dox exhibited pH-dependent drug release behavior due to presence of carboxylic acid groups in the DDS. According to the results, the Alg-Gel/Fe 3 O 4 magnetic hydrogel can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)

The oxidative cleavage of alkenes to the corresponding aldehydes using new amphiphilic carbon quantum dots (A-CQDs) as a pseudohomogeneous carbocatalyst is achieved for the first time through green and sustainable chemical processes. In this work, we successfully design a recyclable pseudohomogeneous catalyst based on A-CQDs, which is decorated with 1-aminopropyl-3-methyl-imidazolium chloride and stearic acid. The functionalization is conducted to introduce a hydrophilic/hydrophobic functionality on the surface of the catalyst to achieve high catalyst availability in polar and nonpolar media with the green goal of eliminating organic (co)solvents and additives. This amphiphilic carbocatalyst provides high mass transferability to the biphasic system, which is beneficial to promoting the oxidative cracking of a variety of olefins into corresponding aldehydes with a substrate/A-CQD ratio of 150. Around 87% of the substrates are converted to the related aldehydes using the carbocatalyst in the presence of H 2 O 2 , in pure water, without using a phase-transfer catalyst or any additives and organic solvents, which is comparable with the current metal-based cleavage systems. Surprisingly, A-CQDs exhibit high catalytic activity for the scission of electron-deficient C═C bond of coumarin derivatives, accompanied by the cleavage of C-O bonds to produce the corresponding salicylaldehyde derivatives without overoxidation to acid. As a brief conclusion, A-CQDs exhibit high conversion efficiency without significant loss of activity even after six catalytic cycles. The conversion of alkenes into aldehydes is fast and high-throughput without overoxidation to acids and is accompanied by excellent solubility and stability in various solvents. Moreover, the product and the catalyst are recoverable from the reaction medium by simple extraction. So, this pseudohomogeneous carbocatalyst promises new horizons in imminent "catalytic age". All in all, this paper provides a significant and novel advancement in carbocatalyst chemistry.

The main focus of the current study is the fabrication of a multifunctional nanohybrid based on graphene oxide (GO)/iron oxide/gold nanoparticles (NPs) as the combinatorial cancer treatment agent. Gold and iron oxide NPs formed on the GONPs via the in situ synthesis approach. The characterisations showed that gold and iron oxide NPs formed onto the GO. Cell toxicity assessment revealed that the fabricated nanohybrid exhibited negligible toxicity against MCF-7 cells in low doses (<50 ppm). Temperature measurement showed a time and dose-dependent heat elevation under the interaction of the nanohybrid with the radio frequency (RF) wave. The highest temperature was recorded using 200 ppm concentration nanohybrid during 40 min exposure. The combinatorial treatments demonstrated that the maximum cell death (average of 53%) was induced with the combination of the nanohybrid with RF waves and radiotherapy (RT). The mechanistic study using the flow cytometry technique illustrated that early apoptosis was the main underlying cell death. Moreover, the dose enhancement factor of 1.63 and 2.63 were obtained from RT and RF, respectively. To sum up, the authors' findings indicated that the prepared nanohybrid could be considered as multifunctional and combinatorial cancer therapy agents.

Despite the recent advances in the treatment strategies of peripheral nerve system defects, peripheral nerve injury (PNI) is still one of the most important health issues with increasing incidence worldwide. The most commonly used treatment approaches are allografts, xenografts, and autologous, which have some drawbacks, including complications, limited source of the donor tissue, tubular collapse, and scar tissue formation. In this context, regenerative medicine has been introduced as a powerful approach to improve the healing process and obtain acceptable functional recovery in the injury site using living cells, scaffold, and bioactive (macro-) molecules. Amongst them, scaffold as a three-dimensional (3D) support biomaterial, structurally bridged the gap or site of injury in order to provide physical and chemical cues to promote correct reinnervation and functional regeneration. Amongst different scaffolding biomaterials, naturally occurring biological macromolecules (more especially proteins and polysaccharides)-based hydrogels exhibited promising results due to their fascinating physicochemical, as well as physiologically relevant properties. This review highlights the recent progress in the development of natural hydrogels-based neural scaffolds. Furthermore, PNI healing process, current status, and challenges are also shortly discussed., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)

Flexibility in the exchange of genetic material takes place between different organisms of the same or different species. This phenomenon is known to play a key role in the genetic, physiological, and ecological performance of the host. Exchange of genetic materials can cause both beneficial and/or adverse biological consequences. Horizontal gene transfer (HGT) or lateral gene transfer (LGT) as a general mechanism leads to biodiversity and biological innovations in nature. HGT mediators are one of the genetic engineering tools used for selective introduction of desired changes in the genome for gene/cell therapy purposes. HGT, however, is crucial in development, emergence, and recurrence of various human-related diseases, such as cancer, genetic-, metabolic-, and neurodegenerative disorders and can negatively affect the therapeutic outcome by promoting resistant forms or disrupting the performance of genome editing toolkits. Because of the importance of HGT and its vital physio- and pathological roles, here the variety of HGT mechanisms are reviewed, ranging from extracellular vesicles (EVs) and nanotubes in prokaryotes to cell-free DNA and apoptotic bodies in eukaryotes. Next, we argue that HGT plays a role both in the development of useful features and in pathological states associated with emerging and recurrent forms of the disease. A better understanding of the different HGT mediators and their genome-altering effects/potentials may pave the way for the development of more effective therapeutic and diagnostic regimes., (Copyright © 2020 Emamalipour, Seidi, Zununi Vahed, Jahanban-Esfahlan, Jaymand, Majdi, Amoozgar, Chitkushev, Javaheri, Jahanban-Esfahlan and Zare.)

The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices. Video abstract.

A novel electrically conductive nanofibrous scaffold based on polyaniline-co-(polydopamine-grafted-poly(d,l-lactide)) [PANI-co-(PDA-g-PLA)] was fabricated using electrospinning technique and its physicochemical as well as biological characteristics toward bone tissue engineering (TE) were investigated extensively. In detail, PANI-co-PDA was synthesized via a one-step chemical oxidization approach. Then, d,l-lactaide monomer was grafted onto PDA segment using a ring opening polymerization (ROP) to afford PANI-co-(PDA-g-PLA) terpolymer. The successful synthesis of PANI-co-(PDA-g-PLA) terpolymer was confirmed using FTIR spectroscopy as well as TGA analysis. Finally, a solution of the synthesized terpolymer was electrospun to fabricate a conductive nanofibrous scaffold. Some physicochemical features such as mechanical, conductivity, electroactivity, hydrophobicity, and morphology as well as biological characteristics including biocompatibility, biodegradability, as well as enhancing the cells adhesion and proliferation were investigated. According to the above-mentioned experimental results, the fabricated electrospun nanofibers can be considered as a potential scaffold for TE application, mainly due to its proper physicochemical and biological properties., Competing Interests: Note The authors declare no competing financial interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nanoparticles are ubiquitous in the environment and are widely used in medical science (e.g. bioimaging, diagnosis, and drug therapy delivery). Due to unique physicochemical properties, they are able to cross many barriers, which is not possible for traditional drugs. Nevertheless, exposure to NPs and their following interactions with organelles and macromolecules can result in negative effects on cells, especially, they can induce cytotoxicity, epigenicity, genotoxicity, and cell death. Lipid-based nanomaterials (LNPs) are one of the most important achievements in drug delivery mainly due to their superior physicochemical and biological characteristics, particularly its safety. Although they are considered as the completely safe nanocarriers in biomedicine, the lipid composition, the surfactant, emulsifier, and stabilizer used in the LNP preparation, and surface electrical charge are important factors that might influence the toxicity of LNPs. According to the author's opinion, their toxicity profile should be evaluated case-by-case regarding the intended applications. Since there is a lack of all-inclusive review on the various aspects of LNPs with an emphasis on toxicological profiles including cyto-genotoxiciy, this comprehensive and critical review is outlined.

It is an unquestionable fact that cancer, also called malignancy, has or will soon become the major global health care problem with an increasing incidence worldwide. Conventional treatment approaches (e.g., radiation or chemotherapy) treat both cancerous and surrounding normal tissues simultaneously, which leads to a poor therapeutic effect on tumors and severe toxic side effects on healthy tissues. Considering these thematic issues, the design and development of more efficient treatment approaches is one of the most important demands of health care in the near future. In this context, the emergence of nanotechnology opens new opportunities for addressing the issues of conventional drug delivery systems (DDSs) for cancer therapy. Theranostic nanomedicines are indebted to the advent of nanotechnology and were introduced by Funkhouser in 2002. These nanomedicines are the newest DDSs that combine diagnostic and therapeutic properties into a single platform. Theranostic nanomedicines are generally composed of targeting agents, diagnostic tracers, effective drug(s), and biomaterial(s) as the matrix to the formulation. Among these, biomaterials have a pivotal role in theranostic nanomedicines due to their direct influence on the system effectiveness. In this context, natural polymers can be considered as potential candidates, mainly due to their inherent physicochemical as well as biological advantages. However, natural polymers have some drawbacks, which can be addressed through the chemical modification approach. In this review, we will highlight the recent progress in the development of theranostic nanomedicines based on chemically modified natural polymers as well as research prospects for the future.

Carbon-based nanomaterials (CNMs) have attracted a great deal of attention because of their outstanding combinations of physicochemical properties. The unique physicochemical properties of CNMs have made them promising nanomaterials (NMs) for a large number of applications. However, these size-dependent properties serve as a double-edged sword, which makes them fascinating materials with specific features. In particular, some health hazards have been associated with exposure to NMs. Among these hazards, genotoxicity has been the subject of intense research due to its role in inducing cancer-causing inheritable mutations. High reactivity, agglomeration tendency, and a high surface-to-volume ratio of CNMs make their interactions with biological moieties unknown, complicated, and multifactorial-dependent. In this regard, the genotoxicity of each part of the CNMs family must be evaluated and considered together with other parameters. Because of the increasing application of CNMs in everyday goods and products, as well as the growth in the potential exposure of humans to CNMs, there is a critical need to assess the genotoxic potential of each part of the CNMs family. Therefore, the main objective of this review is to provide an overview of the potential genotoxicity of CNMs and explore risk assessment strategies to quickly screen and assess emerging CNMs. It is critical to pay equal attention to both nongenotoxic and genotoxic CNMs, because some CNMs identified as nongenotoxic NMs may promote or aid the progression of the tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)