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Two-dimensional MoS2 is emerging as a unique platform for a wide range of biomedical applications including extracellular matrix mimics, drug delivery systems and antimicrobial agents. However, low processability and nonspecific interactions at biointerfaces are serious challenges that hamper the biomedical applications of this nanomaterial. Herein, we show how specific interactions between MoS2 and a gelatin matrix results in a biomimetic hydrogel with the self-healing and molecular recognition properties. β-Cyclodextrin was conjugated to the surface of freshly exfoliated MoS2 through a one pot nucleophilic substitution reaction and the obtained cyclodextrin-functionalized MoS2 was used to construct an injectable, self-healable and flexible supramolecular hydrogel upon host-guest interactions with adamantane-modified gelatin matrix. Incorporation of almost 1 wt% of CDMoS2 into gelatin matrix with 1cm2 cross-section resulted in a hydrogel that was able to tolerate one hundred grams. Also, storage modulus (G′), loss modulus (G″) of the obtained hydrogel was 10 and 25 times higher than that for the neat gelatin, respectively. Due to its self-healing, molecular recognition and mechanical properties as well as its flexibility, injectability, and processability, MoS2gel is a promising candidate for a wide range of future biomedical applications including extracellular matrix mimics and tissue engineering.

Two-dimensional nanomaterials decorated by metal nanoparticles have gained great interest, due to their potential applications in different areas ranging from electrochemical sensing to photothermal therapy. However, metal nanoparticles that are noncovalently immobilized on the surface of two-dimensional nanomaterials can be dissociated from their surface in the complex mediums. This challenge can be overcome by covalent attachment of nanoparticles to the surface of these platforms. In this work, MoS2 sheets are decorated by silver nanoparticles (AgNPs) through a reversible addition-fragmentation chain transfer (RAFT) reaction. Reactive centers were created on the surface of freshly exfoliated MoS2 and a two-dimensional platform with the ability of initiating the RAFT reaction was obtained. Afterwards, silver nanoparticles with acrylamide functionality were synthesized and attached on the surface of MoS2 sheets by the RAFT reaction. MoS2-AgNPs hybrids were characterized by different spectroscopy and microscopy methods as well as thermal and elemental analyses, and then they were used for the electrochemical determination of dipyridamole in aqueous solution. Taking advantage of the straightforward synthesis and the possible MoS2-AgNPs distance adjustment, a variety of hybrid systems with unique physicochemical and optoelectronic properties can be constructed by using this method.

While noncovalent interactions at two-dimensional nanobiointerfaces are extensively investigated, less knowledge about covalent interactions at this interface is available. In this work, boronic acid-functionalized 2D MoS2 was synthesized and its covalent multivalent interactions with bacteria and nematodes were investigated. Polymerization of glycidol by freshly exfoliated MoS2 and condensation of 2,5-thiophenediylbisboronic acid on the produced platform resulted in boronic acid-functionalized 2D MoS2. The destructive interactions between 2D MoS2 and bacteria as well as nematodes were significantly amplified by boronic acid functional groups. Because of the high antibacterial and antinematodal activities of boronic acid-functionalized 2D MoS2, its therapeutic efficacy for diabetic wound healing was investigated. The infected diabetic wounds were completely healed 10 days after treatment with boronic acid-functionalized 2D MoS2, and a normal structure for recovered tissues including different layers of skin, collagen, and blood vessels was detected.

While noncovalent interactions between graphene derivatives and biosystems are extensively studied, less knowledge about their covalent multivalent interactions at biointerfaces is available. Due to the affinity of boronic acids towards cis-diol bearing biosystems, graphene sheets with this functionality were synthesized and their covalent interactions with the bacteria and nematode were investigated. As expected, graphene platforms with boronic acid functionality were able to wrap bacteria and destroy it in a short time. Surprisingly, body of nematodes was ruptured and their viability decreased to 30% after 24 h incubation with the functionalized graphene sheets. Because of their antibacterial and antiparasitic activities as well as their ability for wound dressing, graphene platforms with the boronic acid functionality were further investigated for diabetic wound healing. In vivo experiments showed that graphene platforms are more efficient than the commercially available drug, phenytoin, and restore both infected and non-infected diabetic wounds in ten days. Taking advantage of their straightforward synthesis, strong interactions with different biosystems as well as their ability to heal diabetic wounds, the boronic acid functionalized graphene sheets are promising candidates for a broad range of future biomedical applications.

The attachment of well-defined charge transfer agents to the surface of nanomaterials is an efficient strategy to control their charge density and also to tune their optical, electrical, and physicochemical properties. Particularly interesting are charge transfer agents that either donate or withdraw electrons depending on the arrangements of their building units and that promise a non-destructive attachment to delicate nanomaterials like sp$^2$ compounds. In this work, we rationally synthesize molecular moieties with versatile functionalities. A reactive anchor group allows to attach them to carbon nanotubes as defined charge transfer agents while preserving the tube $\pi$-conjugation. The charge transfer agents were synthesized through the stepwise nucleophilic substitution of either one (monosubstituted series) or two chlorine (disubstituted series) atoms of cyanuric chloride by aniline derivatives containing one, two or three methoxy groups in the para and meta positions. Variation in the number and position of methoxy as an electron transferring group help us to manipulate the electronic and optical properties of the molecular probes and their charge transfer to the SWNTs systematically. The correlation between the optical properties of these molecular probes and their functionality was investigated by experiments and quantum chemical calculations. While the optoelectronic properties of the conjugated charge transfer agents were dominated by the aniline segments, the triazine warrants the ability to nondestructively attach to the surface of SWNTs. This study is one step ahead towards the production of SWNTs with desired optical and electrical properties by covalent $\pi$-preserving functionalization.

Controlled and straightforward functionalization are relevant strategies to obtain MoS2 platforms with defined functionality and improved processability. In this work, an efficient strategy for the functionalization of MoS2 using Reversible Addition Fragmentation Transfer (RAFT) polymerization is reported. The RAFT reagent was directly created on the surface of freshly exfoliated MoS2 and the obtained two-dimensional platform was used for the polymerization of styrene and acrylamide monomers. Various ratios of divinylbenzene were used to crosslink polystyrene brushes and create a polymeric coverage on the surface of MoS2. Furthermore, the polymerization of a mixture of styrene and acrylamide monomers using a MoS2-based RAFT agent resulted in two-dimensional platforms containing copolymer brushes. The structures of the synthesized two-dimensional materials were investigated using different spectroscopy and microscopy techniques as well as thermal and elemental analyses. This research provides an efficient method for the preparation of functional two-dimensional MoS2 nanostructures using RAFT polymerization in gram scale.

Recently, many studies have been focused on the development of graphene-based biosensors. However, they rely on one type of signal and need to be calibrated by other techniques. In this study, a nonenzymatic graphene-based biosensor has been designed and constructed. Its ability to detect glucose and Escherichia coli by three different types of signals has been investigated. For its preparation, dopamine-functionalized polyethylene glycol and 2,5-thiophenediylbisboronic acid were conjugated onto the surface of graphene sheets by nitrene [2 + 1] cycloaddition and condensation reactions, respectively. Multivalent interactions between boronic acid segments and biosystems consequently increased the quantifiable fluorescence emission and UV absorption of dopamine segments. Additionally, changing the electrochemical behavior of the functionalized graphene sheets was possible and resulted in a measurable output signal. Conjugation of mannose onto the surface of the biosensor improved its magnitude of signals and specificity for sensing E. coli in a complex medium. The efficiency and accuracy of each signal was monitored by others, which resulted in a real-time self-calibrating biosensor. Taking advantage of the versatility of the three different indicators, including florescence, UV, and electrochemistry, the functionalized graphene sheets have been used as self-regulating biosensors to detect a variety of biosystems with a high accuracy and specificity in a short time.

An understanding of the interactions of 2D nanomaterials with pathogens is of vital importance to developing and controlling their antimicrobial properties. In this work, the interaction of functionalized graphene with tunable hydrophobicity and bacteria is investigated. Poly(ethylene glycol)- block-(poly- N-isopropylacrylamide) copolymer (PEG- b-PNIPAM) with the triazine joint point was attached to the graphene surface by a nitrene [2 + 1] cycloaddition reaction. By thermally switching between hydrophobic and hydrophilic states, functionalized graphene sheets were able to bind to bacteria. Bacteria were eventually disrupted when the functionality was switched to the hydrophobic state. On the basis of measuring the different microscopy methods and a live/dead viability assay, it was found that Escherichia coli ( E. coli) bacteria are more susceptible to hydrophobic interactions than B. cereus bacteria, under the same conditions. Our investigations confirm that hydrophobic interaction is one of the main driving forces at the presented graphene/bacteria interfaces and promotes the antibacterial activity of graphene derivatives significantly.

2D nanomaterials have garnered widespread attention in biomedicine and bioengineering due to their unique physicochemical properties. However, poor functionality, low solubility, intrinsic toxicity, and nonspecific interactions at biointerfaces have hampered their application in vivo. Here, biocompatible polyglycerol units are crosslinked in two dimensions using a graphene‐assisted strategy leading to highly functional and water‐soluble polyglycerols nanosheets with 263 ± 53 nm and 2.7 ± 0.2 nm average lateral size and thickness, respectively. A single‐layer hyperbranched polyglycerol containing azide functional groups is covalently conjugated to the surface of a functional graphene template through pH‐sensitive linkers. Then, lateral crosslinking of polyglycerol units is carried out by loading tripropargylamine on the surface of graphene followed by lifting off this reagent for an on‐face click reaction. Subsequently, the polyglycerol nanosheets are detached from the surface of graphene by slight acidification and centrifugation and is sulfated to mimic heparin sulfate proteoglycans. To highlight the impact of the two‐dimensionality of the synthesized polyglycerol sulfate nanosheets at nanobiointerfaces, their efficiency with respect to herpes simplex virus type 1 and severe acute respiratory syndrome corona virus 2 inhibition is compared to their 3D nanogel analogs. Four times stronger in virus inhibition suggests that 2D polyglycerols are superior to their current 3D counterparts., A 2D hyperbranched polyglycerol and its sulfated counterpart are synthesized using a graphene‐assisted strategy. The synthesized 2D polymers are used to inhibit the infection by severe acute respiratory syndrome corona virus 2 and show an inhibitory concentration as low as 3 nm.

Search of new strategies for the inhibition of respiratory viruses is one of the urgent health challenges worldwide, as most of the current therapeutic agents and treatments are inefficient. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused a pandemic and has taken lives of approximately two million people to date. Even though various vaccines are currently under development, virus, and especially its spike glycoprotein can mutate, which highlights a need for a broad‐spectrum inhibitor. In this work, inhibition of SARS‐CoV‐2 by graphene platforms with precise dual sulfate/alkyl functionalities is investigated. A series of graphene derivatives with different lengths of aliphatic chains is synthesized and is investigated for their ability to inhibit SARS‐CoV‐2 and feline coronavirus. Graphene derivatives with long alkyl chains (>C9) inhibit coronavirus replication by virtue of disrupting viral envelope. The ability of these graphene platforms to rupture viruses is visualized by atomic force microscopy and cryogenic electron microscopy. A large concentration window (10 to 100‐fold) where graphene platforms display strongly antiviral activity against native SARS‐CoV‐2 without significant toxicity against human cells is found. In this concentration range, the synthesized graphene platforms inhibit the infection of enveloped viruses efficiently, opening new therapeutic and metaphylactic avenues against SARS‐CoV‐2., Present work shows that both electrostatic and hydrophobic interactions play a key role at the graphene/coronavirus interfaces and such materials can efficiently protect cells from coronavirus infections. While electrostatic interactions are responsible for the capturing of viruses, hydrophobic long alkyl chains can disrupt the envelop of the captured virions via hydrophobic interactions leading to a dual effect.

Multidrug resistance resulting from a variety of defensive pathways in cancer has become a global concern with a considerable impact on the mortality associated with the failure of traditional chemotherapy. Therefore, further research and new therapies are required to overcome this challenge. In this work, a cyclic R10 peptide (cR10) is conjugated to polyglycerol-covered nanographene oxide to engineer a nanoplatform for the surmounting of multidrug resistance. The nuclear translocation of the nanoplatform, facilitated by cR10 peptide, and subsequently, a laser-triggered release of the loaded doxorubicin result in efficient anticancer activity confirmed by both in vitro and in vivo experiments. The synthesized nanoplatform with a combination of different features, including active nucleus-targeting, high-loading capacity, controlled release of cargo, and photothermal property, provides a new strategy for circumventing multidrug resistant cancers. National Natural Science Foundation of China http://dx.doi.org/10.13039/501100001809 Natural Science Foundation of Jiangsu Province http://dx.doi.org/10.13039/501100004608 Fundamental Research Funds for the Central Universities http://dx.doi.org/10.13039/501100012226 Iran Science Elites Federation and China Scholarship Council

Interaction of nanoplatforms with biomolecules in biological fluids alters nanoplatforms approach to target tissue and deliver their cargo. Here in, three nanoplatforms were utilized as a carrier to detect the effects of subsequent biomolecules on gene delivery using NIR thermal therapy. Nanoplatforms included; graphene oxide coated gold nanorods (NR@GO), PEGylated NR@GO (NR@GO-PEG) and poly L arginine functionalized NR@GO-PEG (NR@GO-PEG-PLArg). Results indicated that incubation of nanoplatforms in different concentrations of human plasma induced the evolution of layer of proteins (corona) with different thickness on the surface of nanoplatforms. Protein corona decreased the surface charge and optical properties of nanoplatforms. Corona subunits of ITIH, HAS and APOs protein family were extracted from NR@GO-PEG-PLArg surface that play a major role in cellular internalization of nanoplatforms. Moreover, NR@GO-PEG-PLArg remarkably targeted the cancer cells due to uncovered long linear chains of targeting agent (PLArg). The process of gene release and activating apoptotic pathway were enhanced by NIR thermal therapy, which could disrupt the electrostatic interactions and release the protein corona and genes from the surface of nanoplatforms. In conclusion, modification of nanoplatforms with targeting agents could alter the composition of corona toward well interaction with cell and deliver the therapeutic agent.

As resistance to traditional drugs emerges for treatment of virus infections, the need for new methods for virus inhibition increases. Graphene derivatives with large surface areas have shown strong activity against different viruses. However, the inability of current synthetic protocols to accurately manipulate the structure of graphene sheets in order to control their antiviral activity remains a major challenge. In this work, a series of graphene derivatives with defined polyglycerol sulfate and fatty amine functionalities have been synthesized and their interactions with herpes simplex virus type 1 (HSV-1) are investigated. While electrostatic interactions between polyglycerol sulfate and virus particles trigger the binding of graphene to virus, alkyl chains induce a high antiviral activity by secondary hydrophobic interactions. Among graphene sheets with a broad range of alkyl chains, (C3-C18), the C12-functionalized sheets showed the highest antiviral activity, indicating the optimum synergistic effect between electrostatic and hydrophobic interactions, but this derivative was toxic against the Vero cell line. In contrast, sheets functionalized with C6- and C9-alkyl chains showed low toxicity against Vero cells and a synergistic inhibition of HSV-1. This study shows that antiviral agents against HSV-1 can be obtained by controlled and stepwise functionalization of graphene sheets and may be developed into antiviral agents for future biomedical applications.

Multidrug resistance (MDR), which leads tumors resistance to traditional anticancer drugs, can cause the failure of chemotherapy treatments. Herein, we present a new way to overcome this problem using smart multifunctional graphene-based drug delivery systems which can target subcellular organelles and show synergistic hyperthermia and chemotherapy. Mitochondria-targeting ligands are conjugated onto the doxorubicin-loaded, polyglycerol-covered nanographene sheets to actively accumulate them inside the mitochondria after charge-mediated cellular internalization. Upon near-infrared (NIR) irradiation, adenosine triphosphate (ATP) synthesis and mitochondrial function were inhibited and doxorubicin released into the cellular interior. The hyperthermia-accelerated drug release led to a highly selective anticancer efficiency, confirmed by in vitro and in vivo experiments.

A new graphene oxide (GO)-based hydrogel was synthesized through cross-linking of biofunctionalized graphene oxide nanosheets by di-alkyne polyethylene glycol as cross-linking agent. In this respect, nitrene chemistry as a convenient and straightforward protocol was developed for biofunctionalization of GO using an azido-starch as an eco-friendly, biodegradable and cost-effective material. In the next step, 1,3-dipolar cycloaddition chemistry, a green and highly efficient approach was utilized in cross-linking of functionalized GO by PEG through click reaction between remaining azido groups of starch on the surface of GO sheets and terminal alkyne groups of polyethylene glycol. Formation of aziridine and triazole rings during functionalization and cross-linking in this method could evidently improve biological activities of the obtained hydrogel compared to the conventional methods. The antibacterial activity of the new compounds was explored. The synthesized hydrogel showed antibacterial properties against Gram-positive and Gram-negative bacteria due to the presence of triazole rings. Also, the resulting hydrogel exhibited high dye removal efficiency and it can be utilized in water treatment effectively. The adsorption kinetics was analyzed through the effects of adsorption time and the dye concentration on the adsorption capacity. Kinetic data were accurately described by a pseudo-second-order model.

Recent insights into the nanomedicine have revealed that nanoplatforms enhance the efficacy of carrier in therapeutic applications. Here, multifunctional nanoplatforms were utilized in miRNA-101 delivery and NIR thermal therapy to induce apoptosis in breast cancer cells. Au nanorods (NRs) or nanospheres (NSs) covered with graphene oxide (GO) were prepared and functionalized with polyethylene glycol as a stabilizer and poly-L-arginine (P-L-Arg) as a targeting agent. In nanoplatforms, coupling Au@GO prepared stable structures with higher NIR reactivity. P-L-Arg substantially enhanced the cellular uptake and gene retardation of stuffs coated by them. However, rod-shape nanoplatforms indicated better performance in cellular uptake and gene transfection than spherical ones. NIR thermal therapy was implemented to improve gene release and in synergy with miRNA-101 activated the apoptotic pathway and decreased the viability of breast cancer cell (

While curcumin has a broad range of beneficial properties such as anticancer, antioxidant and antibacterial activities, its poor solubility, low stability and non-selectivity toward tumor cells often limit its applications. Herein, we described the preparation and characterization of a new fully biocompatible graft copolymer from folic acid/amylose-functionalized poly(aspartic acid) (FA-PAsp-Am) as an effective nanocarrier using a simple aminolysis method. The inclusion complex formation ability of amylose (Am) with curcumin (Cur) as well as its glycotargeting ability when it grafted to the polyaspartic acid (PAsp) backbone as a side chain, could impart more selectivity to tumor cells, promote the solubility of curcumin and improve its stability against UV–Visible irradiation, as demonstrated by UV–Visible exposure test results. The obtained data from FT-IR, H-NMR, Fluorescence, SEM, DLS and UV–Visible techniques confirmed the successful synthesis of the polymer nanocarrier. The observed nanofiber like morphology (20 nm width by SEM) of the nanocarrier and the host-guest interaction of curcumin with the amylose helices facilitate the high efficiency of the drug loading. The influence of pH, on the curcumin release behavior also was assessed. Furthermore, the antioxidant ability of curcumin was largely maintained after the loading in the FA-PAsp-Am system. These properties collectively make the folic acid (FA) functionalized poly(aspartic acid)-graft-amylose@curcumin of potential interest for various biomedical applications such as targeted drug delivery systems.

Slide ring hydrogels (SRHG) with supramolecular structures are a new class of hydrogels that contrary to the traditional hydrogels comprise dynamic cross-linking points. Herein, we reported on the fabrication of a new slide ring hydrogel through a very convenient one-pot approach. In this regard, isocyanate functionalized GO was synthesized and used as a stopper as well as cross-linker in the presence of a polypseudorotaxane of cyclodextrin threaded on poly(ethylene glycol) (PR). The surface of the resulting SRHG modified via graft polymerization with polyacrylamide (PAAm) and its application as a new type of absorbent for wastewater treatment was studied. Due to its porous structure and its high content of surface functional groups, the synthesized hydrogel was able to efficiently remove cationic dye methylene blue (MB) from wastewater in a short time. The maximum adsorption capacity of the resulting hydrogel was 92.3 mg/g which exhibited an almost 100% increment as compared to that of untreated GO. The adsorption mechanism of MB was also investigated. The kinetic data, obtained at the optimum pH 7, were fitted well with the pseudo-second-order model. Results from degradation and recycling experiments toward MB showed that the SRHG was stable and reusable.

Graphene and its derivatives have recently attracted much attention for sensing and deactivating pathogens. However, the mechanism of multivalent interactions at the graphene-pathogen interface is not fully understood. Since different physicochemical parameters of graphene play a role at this interface, control over graphene's structure is necessary to study the mechanism of these interactions. In this work, different graphene derivatives and also zwitterionic graphene nanomaterials (ZGNMs) were synthesized with defined exposure, in terms of polymer coverage and functionality, and isoelectric points. Then, the switchable interactions of these nanomaterials with E. coli and Bacillus cereus were investigated to study the validity of the generally proposed "trapping" and "nano-knives" mechanisms for inactivating bacteria by graphene derivatives. It was found that the antibacterial activity of graphene derivatives strongly depends on the accessible area, i.e. edges and basal plane of sheets and tightness of their agglomerations. Our data clearly confirm the authenticity of "trapping" and "nano-knives" mechanisms for the antibacterial activity of graphene sheets.

In this work, low molecular weight hyperbranched polyglycerols (LMPGs) are synthesized in bulk using ascorbic acid as an activator. Different molar ratios of glycidol and ascorbic acid were mixed and stirred at ambient conditions and LMPGs with different molecular weights, degree of branching and relative abundance of the structural units were obtained. According to spectroscopy data, ascorbic acid was not incorporated in the structure of the polymer and plays the role of activating agent in the polymerization process. In this synthetic protocol, no other chemical reagents and organic solvents were used. Therefore, products are free of toxic impurities and suitable for future biomedical applications.

In this work, we reported a facile method to produce stable aqueous graphene dispersion through direct exfoliation of graphite by modified hyperbranched polyglycerol. Size of graphene sheets was manipulated by simultaneous exfoliation and sonication of graphite, and functionalized graphene sheets with narrow size distribution were obtained. The polyglycerol-functionalized graphene sheets exhibited highly efficient cellular uptake and photothermal conversion, enabling it to serve as a photothermal agent for cancer therapy.

Citric acid and glycerol play an important role in the food and drug industries. In this work, we present for the first time a facile and gram scale method for the preparation of polyglycerol-citric acid nanoparticles (PGCN) in the presence of silica gel blue as both catalyst and water removal agent. PGCN are highly biocompatible without significant toxicity up to 1 mg/ml. They are able to load small guest molecules and transfer them through the cell membrane, efficiently. Taking advantage of their straightforward synthesis and high biocompatibility as well as their ability to load and transfer small guest molecules, PGCN could be used for a variety of future biomedical applications.

A controlled, reproducible, gram‐scale method is reported for the covalent functionalization of graphene sheets by a one‐pot nitrene [2+1] cycloaddition reaction under mild conditions. The reaction between commercially available 2,4,6‐trichloro‐1,3,5‐triazine and sodium azide with thermally reduced graphene oxide (TRGO) results in defined dichlorotriazine‐functionalized sheets. The different reactivities of the chlorine substituents on the functionalized graphene allow stepwise post‐modification by manipulating the temperature. This new method provides unique access to defined bifunctional 2D nanomaterials, as exemplified by chiral surfaces and multifunctional hybrid architectures.

Single-molecule photoswitchable emitters are demonstrated in the near-infrared based on single-wall carbon nanotube hybrids., The design of single-molecule photoswitchable emitters was the first milestone toward the advent of single-molecule localization microscopy, setting a new paradigm in the field of optical imaging. Several photoswitchable emitters have been developed, but they all fluoresce in the visible or far-red ranges, missing the desirable near-infrared window where biological tissues are most transparent. Moreover, photocontrol of individual emitters in the near-infrared would be highly desirable for elementary optical molecular switches or information storage elements since most communication data transfer protocols are established in this spectral range. Here, we introduce a type of hybrid nanomaterials consisting of single-wall carbon nanotubes covalently functionalized with photoswitching molecules that are used to control the intrinsic luminescence of the single nanotubes in the near-infrared (beyond 1 μm). Through the control of photoswitching, we demonstrate super-localization imaging of nanotubes unresolved by diffraction-limited microscopy.

Although many techniques have been devoted to promote therapeutic purposes of drug carrier systems, however, there are still many challenges in this area. Here, we designed co-loaded delivery systems, composed of curcumin loaded cyclodextrin-graphene oxide core (Cur@CD-GO) and gallic acid loaded chitosan shell nanofibers (Cur-Ga NF), which can promote the therapeutic efficiency of drugs. The synthesized nanofibres were fabricated by electrospinning technique with the coaxial system. Results showed that co-loaded delivery systems (Cur-Ga NF) provide better performance over single drug-loaded NFs (Cur@CD-GO). It was demonstrated that the nanofibers were successfully prepared, and the drugs in the core and sell of nanofibers were released in a controlled and sustained manner. The produced Cur-Ga NF, providing improved anti-cancer activity, antimicrobial activity, antioxidant activity and anti-inflammatory outcome as compared to single drug-loaded NFs. Our investigations showed that such co-delivery fiber systems could be employed as a promising nanocarrier for therapeutic applications.

Inhibition of respiratory viruses is one of the most urgent topics as underlined by different pandemics in the last two decades. This impels the development of new materials for binding and incapacitation of the viruses. In this work, we have demonstrated that an optimal deployment of influenza A virus (IAV) targeting ligand sialic acid (SA) on a flexible 2D platform enables its binding and wrapping around IAV particles. A series of 2D sialylated platforms consisting graphene and polyglycerol are prepared with different degrees of SA functionalization around 10%, 30%, and 90% named as G-PG-SAL, G-PG-SAM, and G-PG-SAH, respectively. The cryo-electron tomography (Cryo-ET) analysis has proved wrapping of IAV particles by G-PG-SAM. A confocal-based colocalization assay established for these materials has offered the comparison of binding potential of sialylated and non-sialylated nanoplatforms for IAV. With this method, we have estimated the binding potential of the G-PG-SAM and G-PG-SAH sheets for IAV particles around 50 and 20 times higher than the control sheets, respectively, whereas the low functionalized G-PG-SAL have not shown any significant colocalization value. Moreover, optimized G-PG-SAM exhibits high potency to block IAV from binding with the MDCK cells.

Metal-based nanoentities, apart from being indispensable research tools, have found extensive use in the industrial and biomedical arena. Because their biological impacts are governed by factors such as size, shape, and composition, such issues must be taken into account when these materials are incorporated into multi-component ensembles for clinical applications. The size and shape (rods, wires, sheets, tubes, and cages) of metallic nanostructures influence cell viability by virtue of their varied geometry and physicochemical interactions with mammalian cell membranes. The anisotropic properties of nonspherical metal-based nanoarchitectures render them exciting candidates for biomedical applications. Here, the size-, shape-, and composition-dependent properties of nonspherical metal-based nanoarchitectures are reviewed in the context of their potential applications in cancer diagnostics and therapeutics, as well as, in regenerative medicine. Strategies for the synthesis of nonspherical metal-based nanoarchitectures and their cytotoxicity and immunological profiles are also comprehensively appraised.

Hyperbranched polyglycerols (hPGs) have a variety of biomedical applications due to their unique physicochemical properties such as biocompatibility and multi-functionality. However, their lack of biodegradability under physiological conditions hampers their in vivo applications. Therefore, the development of straightforward methods for the synthesis of biodegradable hyperbranched polyglycerols is of great importance. In this work, caprolactone segments were incorporated into the backbone of polyglycerols by a one-pot, ring-opening copolymerization of glycidol and e-caprolactone under ambient conditions. While the synthesized polyglycerols were susceptible to enzymatic cleavage, they were stable under neutral and acidic conditions. In spite of their high cellular uptake that was proven by laser scanning confocal microscopy (LSCM), the MTT assay did not show a significant toxicity against HaCaT cells up to 1000 μg ml−1. The biodegradability and biocompatibility of the synthesized polymers together with their ability to form nanoparticles in aqueous solutions and loading of hydrophobic guest molecules encourage us to evaluate their application as intradermal delivery systems. Ex vivo skin penetration tests showed that the synthesized polymers enhanced the Nile red penetration into the skin upon enzymatic degradation. While polymers stayed at the superficial stratum corneum, the released cargo penetrated into the deeper layers of the skin.

In this work we report on a new method for the cationic polymerization of glycidol by citric acid at ambient and solvent free conditions. In this polymerization, citric acid is a proton donor and is able to incorporate in the structure of polyglycerol by reaction with the activated monomer. The molecular weight and degree of branching of the synthesized polymers are affected by the glycidol/citric acid molar ratios and reaction temperature. Due to the citric acid core of the hyperbranched polyglycerols, they are able to break down into the smaller segments at neutral or acidic conditions. Apart from citric acid, glycidol, and water, other reagents or organic solvents have not been used in the synthetic and purification processes. Taking advantage of the green synthesis and ability to cleave under physiological conditions, in addition to the intrinsic biocompatibility of polyglycerol, the synthesized polymers are promising candidates for future biomedical applications.

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.

Akram Assali,1 Omid Akhavan,2 Fatemeh Mottaghitalab,1 Mohsen Adeli,3 Rassoul Dinarvand,1 Shayan Razzazan,4 Ehsan Arefian,5 Masoud Soleimani,6 Fatemeh Atyabi1 1Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Physics, Sharif University of Technology, Tehran, Iran; 3Department of Biology, Chemistry, Pharmacy, Institute of Chemistry and Biochemistry, Freie University Berlin, Berlin, Germany; 4Department of Electrical Engineering, Amirkabir University of Technology, Tehran, Iran; 5Molecular Virology Lab, Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran; 6Hematology Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Introduction: MicroRNA-101 (miR-101) is an intense cancer suppressor with special algorithm to target a wide range of pathways and genes which indicates the ability to regulate apoptosis, cellular stress, metastasis, autophagy, and tumor growth. Silencing of some genes such as Stathmin1 with miR-101 can be interpreted as apoptotic accelerator and autophagy suppressor. It is hypothesized that hybrid microRNA (miRNA) delivery structures based on cationized graphene oxide (GO) could take superiority of targeting and photothermal therapy to suppress the cancer cells.Materials and methods: In this study, GO nanoplatforms were covalently decorated with polyethylene glycol (PEG) and poly-L-arginine (P-L-Arg) that reduced the surface of GO and increased the near infrared absorption ~7.5-fold higher than nonreduced GO.Results: The prepared nanoplatform [GO-PEG-(P-L-Arg)] showed higher miRNA payload and greater internalization and facilitated endosomal scape into the cytoplasm in comparison with GO-PEG. Furthermore, applying P-L-Arg, as a targeting agent, greatly improved the selective transfection of nanoplatform in cancer cells (MCF7, MDA-MB-231) in comparison with immortalized breast cells and fibroblast primary cells. Treating cancer cells with GO-PEG-(P-L-Arg)/miR-101 and incorporating near infrared laser irradiation induced 68% apoptosis and suppressed Stathmin1 protein.Conclusion: The obtained results indicated that GO-PEG-(P-L-Arg) would be a suitable targeted delivery system of miR-101 transfection that could downregulate autophagy and conduct thermal stress to activate apoptotic cascades when combined with photothermal therapy. Keywords: miR-101, cationized graphene oxide, poly-L-arginine, apoptosis, autophagy, photothermal therapy

Amphiphilic hyperbranched polymers and copolymers consisting of polyglycerol, polycitric acid and a p-sulfonatocalix[4]arene core (HPCs) were synthesized and characterized. Depending on the composition of AHPs, their self-assembly in aqueous solution led to different nano and microtubes with the ability of encapsulation of anticancer drugs such as curcumin.

Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water-soluble fullerene-polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV-G) with baby hamster kidney cells serving as a model of host cell. Interference with L-selectin-ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)-based inhibition assay and the leukocyte cell (NALM-6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico- to nanomolar half maximal inhibitory concentrations (IC50 ) are achieved. With their highly antiviral and anti-inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.

Recently, graphene oxide (GO), as a two-dimensional carbon nanomaterial, has received a surge of attention in the scientific communities due to its unique structure and properties. The GO-based hydrogels have been prepared using different strategies such as acidification or by addition of organic molecules, polymers, or ions as crosslinkers which could crosslink them by covalent and supramolecular interactions such as H-bonding, coordination interactions, and hydrophobic interactions. Similarly, hydrogels based on chemically modified or grafted GO have been also reported. GO-based composites and hydrogels due to their unique features broadly examined for numerous applications such as wastewater treatment, catalysis, biomedical applications, energy storage devices, supercapacitors, and sensors. To meet the demands of such applications, assembling of graphene-based nanolayers into three-dimensional gel-like networks is the main issue that should be considered. This chapter reviews some recent progress on 3D GO-based composites and gels.

Fluorescent nanomaterials are expected to revolutionize medical diagnostic, imaging, and therapeutic tools due to their superior optical and structural properties. Their inefficient water solubility, cell permeability, biodistribution, and high toxicity, however, limit the full potential of their application. To overcome these obstacles, a water-soluble, fluorescent, cytocompatible polymer-single-walled carbon nanotube (SWNT) complex is introduced for bioimaging applications. The supramolecular complex consists of an alkylated polymer conjugated with neutral hydroxylated or charged sulfated dendronized perylene bisimides (PBIs) and SWNTs as a general immobilization platform. The polymer backbone solubilizes the SWNTs, decorates them with fluorescent PBIs, and strongly improves their cytocompatibility by wrapping around the SWNT scaffold. In photophysical measurements and biological in vitro studies, sulfated complexes exhibit superior optical properties, cellular uptake, and intracellular staining over their hydroxylated analogs. A toxicity assay confirms the highly improved cytocompatibility of the polymer-wrapped SWNTs toward surfactant-solubilized SWNTs. In microscopy studies the complexes allow for the direct imaging of the SWNTs' cellular uptake via the PBI and SWNT emission using the 1st and 2nd optical window for bioimaging. These findings render the polymer-SWNT complexes with nanometer size, dual fluorescence, multiple charges, and high cytocompatibility as valuable systems for a broad range of fluorescence bioimaging studies.

Since therapeutic agents target specific compartments inside the cells, their efficiency depends on their intracellular release from drug delivery systems (DDS). However, control over the intracellular release of therapeutic agents is a challenging issue and can only be achieved by governing their interactions with the DDS. In this work, polyglycerol amine- and polyglycerol sulfate-functionalized graphene sheets as positively and negatively charged 2D nanomaterials with 150 nm lateral size were used to deliver and control the release of doxorubicin (DOX) inside cells. A pH-sensitive dye was conjugated onto the surfaces of graphene sheets and used as an antenna to obtain specific signals from the acidic cell compartments. It was found that both positively and negatively charged graphene sheets undergo similar acidification processes after cellular uptake. Nevertheless, the intracellular drug release of these DOX-loaded nanomaterials was distinctly different. As an overall effect of the π-π stacking and electrostatic interactions, the release of DOX from the positively charged graphene sheets was much faster than that from their analogs with a negative surface charge. Therefore, therapeutic efficiency in the first case was much higher than that in the latter. Based on our findings, the intracellular release of drugs from the surfaces of graphene sheets can be finely tuned by manipulating their functionalities, which is of great importance in the designing of the future graphene-based nanomedicines.

2D nanomaterials, particularly graphene, offer many fascinating physicochemical properties that have generated exciting visions of future biological applications. In order to capitalize on the potential of 2D nanomaterials in this field, a full understanding of their interactions with biointerfaces is crucial. The uptake pathways, toxicity, long-term fate of 2D nanomaterials in biological systems, and their interactions with the living systems are fundamental questions that must be understood. Here, the latest progress is summarized, with a focus on pathogen, mammalian cell, and tissue interactions. The cellular uptake pathways of graphene derivatives will be discussed, along with health risks, and interactions with membranes-including bacteria and viruses-and the role of chemical structure and modifications. Other novel 2D nanomaterials with potential biomedical applications, such as transition-metal dichalcogenides, transition-metal oxide, and black phosphorus will be discussed at the end of this review.

Due to their unique structure and properties, water-soluble fullerene derivatives are of great interest for various biomedical purposes. In this work, solution behavior, encapsulation and release properties, biocompatibility, and cellular uptake pathways of fullerene-polyglycerol amphiphiles (FPAs) with defined structures are investigated. The number of polyglycerol branches attached to the surface of fullerene affects the physicochemical properties of FPAs dramatically but not their cellular uptake. Release of encapsulated hydrophobic dyes from FPAs strongly depends on the number of their branches. Conjugation of a pH-sensitive dye to the FPAs as a probe showed that their self-assemblies are taken up through endocytotic pathways. It was observed that FPAs are able to transfer small molecules into cells both above and below their critical aggregation concentration. Taking advantage of the water solubility, biocompatibility, and transfer-ability of FPAs, they might find use as unimolecular carriers for future biomedical applications.

A new method for top-down, one-pot, gram-scale production of high quality nanographene by incubating graphite in a dilute sodium hypochlorite solution at only 40 °C is reported here. The produced sheets have only 4 at% oxygen content, comparable with nanographene grown by chemical vapor deposition. The nanographene sheets are covalently functionalized using a nondestructive nitrene [2+1] cycloaddition reaction that preserves their π-conjugated system. Statistical analyses of Raman spectroscopy and X-ray photoelectron spectroscopy indicate a low number of sp3 carbon atoms on the order of 2% before and 4% after covalent functionalization. The nanographene sheets are significantly more conductive than conventionally prepared nanographene oxide, and conductivity further increases after covalent functionalization. The observed doping effects and theoretical studies suggest sp2 hybridization for the carbon atoms involved in the [2+1] cycloaddition reaction leading to preservation of the π-conjugated system and enhancing conductivity via n-type doping through the bridging N-atom. These methods are easily scalable, which opens the door to a mild and efficient process to produce high quality nanographenes and covalently functionalize them while retaining or improving their physicochemical properties.

In this work, we report a new method for the synthesis of graphene oxide (GO) using cyanuric chloride as a non-corrosive oxidizing agent. The mild conditions, simple purification, and scalability of this method are significant advantages over common approaches in which harsh oxidizing agents are used. Moreover, a major drawback with the Hummers' method, the production of toxic gases, is not an issue with this process. This method is a safe and large-scale alternative for the production of GO under mild conditions.

In this study, graphene oxide - cellulose nanowhiskers nanocomposite hydrogel was easily synthesized through covalent functionalization of cellulose nanowhiskers with graphene oxide via a facile approach. The nitrene chemistry applied for covalent functionalization of graphene oxide sheets. The surface morphology and chemical structure of the nanocomposite hydrogel were characterized by FTIR, TGA, Raman, XRD, elemental analysis and SEM. The UV/Visible absorption spectrum revealed that the obtained porous nanocomposite hydrogel can efficiently remove cationic dyes such as methylene blue (MB) and Rhodamine B (RhB) from wastewater with high absorption power. The adsorption process showed that 100% of MB and 90% of RhB have been removed and the equilibrium state has been reached in 15min for low concentration solutions in accordance with the pseudo-second-order model. Moreover, the sample exhibited stable performance after being used several times. High adsorption capacity and easy recovery are the efficient factors making these materials as good adsorbent for water pollutants and wastewater treatment.

Covalent functionalization tailors carbon nanotubes for a wide range of applications in varying environments. Its strength and stability of attachment come at the price of degrading the carbon nanotubes sp2 network and destroying the tubes electronic and optoelectronic features. Here we present a non-destructive, covalent, gram-scale functionalization of single-walled carbon nanotubes by a new [2+1] cycloaddition. The reaction rebuilds the extended π-network, thereby retaining the outstanding quantum optoelectronic properties of carbon nanotubes, including bright light emission at high degree of functionalization (1 group per 25 carbon atoms). The conjugation method described here opens the way for advanced tailoring nanotubes as demonstrated for light-triggered reversible doping through photochromic molecular switches and nanoplasmonic gold-nanotube hybrids with enhanced infrared light emission., While covalent modification of carbon nanotubes allows their use in a wide range of applications, it often results in disruption of their optoelectronic properties. Here, the authors design a cycloaddition reaction that preserves the nanotubes electronic structure.

Here, we report for the first time a facile method for the preparation of novel drug delivery systems based on supramolecular interactions between β-cyclodextrin-polyglycerol conjugates (β-CD-g-PG) and human serum albumin (HSA). The results obtained by combined experimental/modeling studies showed that the main drivers to the formation of HSA/β-CD-g-PG supramolecular entities are host–guest interactions between β-CD-g-PG and the aromatic side-chains of HSA residues. Due to these interactions, HSA undergoes a confined yet fundamental conformational transition, leading to greater exposure of the hydrophobic protein domains available to hydrophobic drug binding. Next, the binding affinity and loading capacity of the HSA/β-CD-g-PG supramolecular nanovector for doxorubicin (DOX) and paclitaxel (PTX) were investigated. Both drug/HSA binding constants (Kb,HSA/DOX = 3.24 × 103 M−1 and Kb,HSA/PTX = 5.65 × 101 M−1) sensibly increased in the presence of β-CD-g-PG (Kb,HSA/β-CD-g-PG/DOX = 2.78 × 104 M−1 and Kb,HSA/β-CD-g-PG/PTX = 2.82 × 102 M−1). In line, both protein drug loadings increased by about 20% upon HSA/β-CD-g-PG interaction (80% and 71% for DOX and PTX, respectively) with respect to the loading capacity of the bare HSA (60% and 50%). Due to the improved loading capacity with minimal changes in the structure of HSA, this system is a promising vector for future cancer therapy.

Polysulfated nanomaterials that mimic the extracellular cell matrix are of great interest for their potential to modulate cellular responses and to bind and neutralize pathogens. However, control over the density of active functional groups on such biomimetics is essential for efficient interactions, and this remains a challenge. In this regard, producing polysulfated graphene derivatives with control over their functionality is an intriguing accomplishment in order to obtain highly effective 2D platforms for pathogen interactions. Here, a facile and efficient method for the controlled attachment of a heparin sulfate mimic on the surface of graphene is reported. Dichlorotriazine groups are conjugated to the surface of graphene by a one-pot [2+1] nitrene cycloaddition reaction at ambient conditions, providing derivatives with defined functionality. Consecutive step by step conjugation of hyperbranched polyglycerol to the dichlorotriazine groups and eventual conversion to the polyglycerol sulfate result in the graphene based heparin biomimetics. Scanning force microscopy, cryo-transmission electron microscopy, and in vitro bioassays reveal strong interactions between the functionalized graphene (thoroughly covered by a sulfated polymer) and vesicular stomatitis virus. Infection experiments with highly sulfated versions of graphene drastically promote the infection process, leading to higher viral titers compared to nonsulfated analogues.

Multidomain polymeric nanoparticles containing different blocks with different properties have gained great interest for a wide range of applications in the past two decades. In this work, core multishell (CMS) structures consisting of hyperbranched polyglycerol as core and polylactide and polycaprolactone as shell structures are presented. Number of arms and thickness of shells have been manipulated by precise control over the molar ratios of monomer to terminal functional groups in the reaction feed. The ability of CMS to load and release small guest molecules and also the loading capacities are studied using Rose Bengal as a model dye. Loading capacity of CMS depends on molecular weight, type, and thickness of shells. Due to the difference in polarity and solubility of different blocks, the CMS nanocarriers show medium-responsive behavior whereupon the encapsulated guest molecules are released in a controlled manner.

Hybrid nanomaterials consisting of functionalized fullerene and gold nanoparticle (NP) have been synthesized. Fullerene was functionalized by citric acid and used as reducing and capping agent for preparation of gold NPs. Functionalization of fullerene by use of citric acid was performed by enzymatic and thermal approaches. The core-shell structures containing gold NPs as core and fullerene as shell (gold/fullerene) were prepared. It was found that method and density of functionalization of fullerene effect final structure and therefore their physicochemical property of hybrid nanomaterial dramatically. Ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM) were used to analyze the structure of the synthesized hybrid nanomaterial and also study their self-assembly and physicochemical properties. Effect of the size, structure and morphology (e.g., agglomeration) of the synthesized hybrid nanomaterial on their UV-Vis absorption behavior has been also verified by theoretical modeling.

In this work, we report a new, simple, gram-scale method for synthesizing water-soluble fullerene-polyglycerol amphiphiles (FPAs) that self-assemble into partially and fully crosslinked nanoclusters with the ability to controllably transport hydrophobic and hydrophilic agents.