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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.

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.

The present research aimed to use the concept of willingness to use and the ordinal logit model to evaluate the factors influencing the adoption of date palm leaf waste (PLW) by ranchers in the south of Kerman province in 2020. Data were collected by filling in 202 questionnaires by ranchers randomly selected at the study site. Based on the results, about 51 percent of the ranchers in the study site are reluctant to use PLW so that only 46 ranchers in the studied sample expressed their willingness to use it. The results of the ordinal logit model show that the willingness to use PLW in animal feeding increases with increasing the rancher’s ranching history, providing his/her with information for awareness enhancement, decreasing his/her concerns over the feedback of using PLW in animal feeding, and finally, membership in a cooperative. Also, the likelihood of PLW use in animal feeding is higher in large-sized animal farms than in small-sized ones (sheep and goats). Based on the results, to extend the use of PLW in animal feeding, it is necessary to take promoting actions among the ranchers in the study site to ensure them about the health of this feed for their animals. In addition, PLW suppliers can be provided with some facilities to supply their product in the market, and demonstration farms where this product is consumed can be used to reduce the wastage of this commercially capable product.

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

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.

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.

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.

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.

Hyperbranched polyglycerol (hPG) with two different molecular weights (hPG2400 and hPG8000) was used as a macroinitiator for the polymerization of lactide. Thereby, amphiphilic linear-dendritic multiarm star copolymers (MSCs) were prepared and investigated with regard to their ability to encapsulate and transport guest molecules. Various ratios of monomer to hydroxy functional end groups ([LA]/[OH]) were used for the preparation of linear-dendritic multiarm copolymers with different degrees of polymerization (DP), molecular weight, and arm multiplicity. At high molecular weights almost all of the hydroxy groups of hPG were reacted with the lactide monomer and the number of arms was equal to the number of hydroxy functional groups. The ability of the synthesized MSCs to encapsulate and transport small guest molecules was examined. The transport capacity (TC) of all nanocarriers under different conditions was investigated using the model dye Congo red as well as the model drug 5-aminosalicylic acid (5-ASA). With both hPG2400 and hPG8000 cores, the TC increased along with an increasing number and length of the arms. The dependence of the TC on the concentration of MSCs was also investigated and found to deteriorate with increasing polymer concentration. Finally the ability of the synthesized nanocarriers to penetrate into the skin and transport Nile red through this barrier was successfully investigated.

Here we report for the first time a microwave assisted synthesis of polyglycerol dendron functionalized cyclodextrins (CD) with hydrophobic tails. These amphiphilic CDs consist of seven polyglycerol dendrons and fourteen alkyl chains on the primary and secondary rims of the cyclodextrin core, respectively. They self-assemble to form nanostructures in aqueous solutions and efficiently encapsulate hydrophobic aromatic guests. The size and shape of the self-assemblies and also their ability to encapsulate guest molecules depend on the generation of conjugated polyglycerol dendrons.

Z Sobhani1, R Dinarvand1,2, F Atyabi1,2, M Ghahremani3, M Adeli4,51Department of Pharmaceutics, 2Nanotechnology Research Center, 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran; 4Department of Chemistry, Sharif University of Technology, Tehran; 5Department of Chemistry, Faculty of Science, Lorestan University, Khoramabad, IranAbstract: Potential applications of carbon nanotubes have attracted many researchers in the field of drug delivery systems. In this study, multiwalled carbon nanotubes (MWNTs) were first functionalized using hyperbranched poly citric acid (PCA) to improve their hydrophilicity and functionality. Then, paclitaxel (PTX), a potent anticancer agent, was conjugated to the carboxyl functional groups of poly citric acid via a cleavable ester bond to obtain a MWNT-g-PCA-PTX conjugate. Drug content of the conjugate was about 38% (w/w). The particle size of MWNT-g-PCA and MWNT-g-PCA-PTX was approximately 125 and 200 nm, respectively. Atomic force microscopy and transmission electron microscopy images showed a curved shape for MWNT-g-PCA and MWNT-g-PCA-PTX, which was in contrast with the straight or linear conformation expected from carbon nanotubes. It seems that the high hydrophilicity of poly citric acid and high hydrophobicity of MWNTs led to conformational changes from a linear state to a curved state. Paclitaxel can be released from the MWNT-g-PCA-PTX conjugates faster at pH 6.8 and 5.0 than at pH 7.4, which was suitable for the release of the drug in tumor tissues and tumor cells. In vitro cytotoxicity studies were evaluated in the A549 and SKOV3 cell lines. MWNT-g-PCA had an insignificant cytotoxic effect on both cell lines. MWNT-g-PCA-PTX had more of a cytotoxic effect than the free drug over a shorter incubation time (eg, 24 hours versus 48 hours), which suggests improved cell penetration of MWNT-g-PCA-PTX. Therefore, paclitaxel conjugated to MWNT-g-PCA is promising for cancer therapeutics.Keywords: multiwalled carbon nanotubes, functionalization, anticancer, drug delivery, nanoparticles