Nanomaterials for Targeted Delivery of Agrochemicals by an All-in-One Combination Strategy and Deep Learning.

The development of modern agriculture has prompted the greater input of herbicides, insecticides, and fertilizers. However, precision release and targeted delivery of these agrochemicals still remain a challenge. Here, a pesticide-fertilizer all-in-one combination (PFAC) strategy and deep learning are employed to form a system for controlled and targeted delivery of agrochemicals. This system mainly consists of three components: (1) hollow mesoporous silica (HMS), to encapsulate herbicides and phase-change material; (2) polydopamine (PDA) coating, to provide a photothermal effect; and (3) a zeolitic imidazolate framework (ZIF8), to provide micronutrient Zn2+ and encapsulate insecticides. Results show that the PFAC at concentration of 5 mg mL-1 reaches the phase transition temperature of 1-tetradecanol (37.5 °C) after 5 min of near-infrared (NIR) irradiation (800 nm, 0.5 W cm-2). The data of corn and weed are collected and relayed to deep learning algorithms for model building to realize object detection and further targeted weeding. In-field treatment results indicated that the growth of chicory herb was significantly inhibited when treated with the PFAC compared with the blank group after 24 h under NIR irradiation for 2 h. This system combines agrochemical innovation and artificial intelligence technology, achieves synergistic effects of weeding and insecticide and nutrient supply, and will potentially achieve precision and sustainable agriculture.

A nano polymer conjugate for dual drugs sequential release and combined treatment of colon cancer and thrombotic complications.

Thrombotic complications turn into the second leading cause of death in colon cancer patients due to the hypercoagulable state caused by malignancy. Therefore, it is necessary to treat colon cancer and its thrombosis complications simultaneously. Herein, a nano polymer conjugate based on disulfide cross-linked low-generation peptide dendrimers was developed to treat colon cancer and its thrombotic complications. First, two-generation polyglutamic acid dendrimer was bonded to nattokinase (NK) and then cross-linkers containing disulfide linkages were used to obtain polymer conjugates (NK-G2)n. Then doxorubicin (Dox) was encapsulated. The system can release drugs sequentially due to the dissociation of the polymer conjugates. In vitro thrombolytic experiments exhibited a significant thrombolysis ability of (NK-G2)n. The toxicity and cellular uptake tests on HCT116 cells showed that Dox loaded polymer conjugates had good endocytosis ability and anti-cancer effect. Therefore, this drug delivery system will be a promising strategy to the combined treatment of colon cancer and thrombotic complications.

A multielement compound fertilizer used polydopamine and sodium carboxymethyl starch matrices as coatings.

In this work, a multielement compound fertilizer (MCF) was fabricated using ammonium zinc phosphate (AZP) as kernel nutrient element, and polydopamine (Pdop) film as inner coating. Besides, sodium carboxymethyl starch (SCS) was proposed as a constituent in AZP@Pdop mixture due to its adhesion, gelling and swelling abilities, to prepare well dispersed suspensions and consolidate the single-coated fertilizer. What's more, iron (Fe), the vital microelement for the growth of crops and alleviating the leaf chlorosis, was chelated by the carboxylate groups of SCS, contributing to make the outer coating compact. The release behavior showed that zinc (Zn), phosphorus (P) and Fe reached 60% cumulative release in 30 days, and the use efficiency of nutrients for corn was about 60%. In summary, this work provides a novel approach to improve the utilization efficiency and prolong duration of the MCF, which might have a potential application in agronomics.

Synthesis and characterization of a nano fluorescent starch.

A novel nano fluorescent starch, starch-bearing 3-epoxypropoxy fluorescein (ST-EF) was developed by a simple method. First, 3-epoxypropoxy fluorescein (EF) was prepared via a nucleophilic substitution reaction between fluorescein and epichlorohydrin. Then, ST-EF was synthesized via a ring-opening reaction to attach fluorescein to native cassava starch chains. The degree of substitution (DS) of ST-EF was determined by ultraviolet-visible spectrophotometry. The 1H nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, fourier transformed infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize ST-EF. Fluorescent properties of ST-EF in water were studied. The results showed that the nano fluorescent starch shows strong fluorescence as fluorescein, and can be used as a fluorescent polymer in various applications, especially in biomedicine.

Multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus.

Thrombotic events affect many individuals in a number of ways, all of which can cause significant morbidity and mortality. Nattokinase (NK), as a novel thrombolytic drug, has been used for thrombolytic therapy. It not only possesses plasminogen activator activity, but also directly digests fibrin through limited proteolysis. However, it may undergo inactivation and denaturation in the harsh external environment. In this study, a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer was fabricated and used as a carrier for NK protection and delivery. Different arm numbers of polyethylene glycol-polyglutamic acid peptide dendrimers (x-PEG(G3 )x , x = 2, 4, 6, 8) were designed, prepared, and characterized by 1 H NMR and FTIR. Then, x-PEG(G3 )x were loaded with NK to form nanocomposites. Their size and morphology were determined by dynamic light scattering and transmission electron microscopy. Enzyme activity was evaluated via UV-Vis absorbance spectra, fluorescence spectra, circular dichroism spectra, and zeta potential measurements. The study reveals that the obtained x-PEG(G3 )x /NK nanocomposites possess high enzyme activity. In addition, the nanocomposites show increased viability of rat macrophage cells, and excellent thrombolysis ability in vitro and in vivo. This work establishes a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer with potential application in NK carrier and thrombolytic therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1687-1696, 2018.

High encapsulation and localized delivery of curcumin from an injectable hydrogel.

Most chemotherapy currently available for cancer treatment has limited potential to successful clinical cancer therapy, mainly due to low encapsulating capacity of drugs and unavailable pharmacologically beneficial concentrations at the tumor site. Herein, a novel yet simple strategy is developed to enhance drug encapsulating capacity and localized drug concentration using an injectable hydrogel based on thiolated chitosan (TCS) and poly(ethylene glycol) diacrylate (PEGDA). Almost 100% of encapsulating capacity is achieved when anti-cancer drug curcumin is encapsulated in the system. The interaction of curcumin with PEGDA is determined by fluorescence spectroscopy and the binding constant is calculated, followed by a simulation by a docking study using AutoDock. To improve the anti-tumor activity and achieve effective local concentrations, lysozyme is introduced into the system. Sustained curcumin release in a controlled lysozyme-responsive behaviour is observed, which enables the drug concentration to reach the therapeutic threshold promptly. The system displays efficient intracellular curcumin release to promote cancer cells apoptosis in vitro. In addition, the system effectively delays the tumor growth and reduces adverse effects in tumor-bearing nude mice. The strategy of localized, high encapsulation of drug by using an injectable hydrogel would be particularly beneficial with many insoluble anti-cancer drugs.

Dual crosslinked chondroitin sulfate injectable hydrogel formed via continuous Diels-Alder (DA) click chemistry for bone repair.

In the present work, a thermosensetive copolymer with a low gelation concentration under 37°C, F127@ChS (F127 crosslinked chondroitin sulfate) was synthesized via DA click chemistry between F127-AMI (maleimido terminated F127) and ChS-furan (furfurylamine grafted chondroitin sulfate). Then, dual crosslinked hydrogels were prepared based on F127@ChS and PEG-AMI (maleimido terminated polyethylene glycol). The physical crosslinking of F127@ChS affords the hydrogel fast gelation behavior, while in situ DA click reaction occurred between F127@ChS and PEG-AMI affords the hydrogel system covalent crosslinking. The dual crosslinked injectable hydrogel was applied as scaffold to load BMP-4 for rat cranial defect repair. As indicated by X-ray imaging, cranial digital images and histological (HE and Masson) staining analysis, new bone tissues were formed in the defected area after 12 weeks repair. The results demonstrate that the novel dual crosslinked injectable hydrogel offer an interesting option for cranial bone tissue engineering.

CO2-switchable fluorescence of a dendritic polymer and its applications.

The synthesis and properties of CO2 responsive and fluorescent dendritic polymers, poly(amido amine)/Pluronic F127 (PAMAM/F127), are reported in this paper. The morphologies and sizes of PAMAM/F127 dendritic polymers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). PAMAM/F127 dendritic polymers showed unimolecular micelle morphologies at low concentrations, and changed to multimolecular micelles at higher concentrations. Additionally, fluorescence spectra and confocal laser scanning microscopy images showed that PAMAM/F127 dendritic polymers exhibited a fluorescent enhancement response to the presence of CO2. Apart from that, the release behavior of PAMAM/F127 gels under simulated body fluids was investigated by choosing curcumin as the hydrophobic drug. The results indicated that PAMAM/F127 dendritic polymers can be used to improve the solubility of curcumin, and the drug released faster in the presence of CO2. Such CO2 responsive fluorescent dendritic polymers are potentially applicable in cellular imaging or drug controlled release.

Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease.

Injectable and Self-Healing Carbohydrate-Based Hydrogel for Cell Encapsulation.

With the fast development of cell therapy, there has been a shift toward the development of injectable hydrogels as cell carriers that can overcome current limitations in cell therapy. However, the hydrogels are prone to damage during use, inducing cell apoptosis. Therefore, this study was carried out to develop an injectable and self-healing hydrogel based on chondroitin sulfate multiple aldehyde (CSMA) and N-succinyl-chitosan (SC). By varying the CSMA to SC ratio, the hydrogel stiffness, water content, and kinetics of gelation could be controlled. Gelation readily occurred at physiological conditions, predominantly due to a Schiff base reaction between the aldehyde groups on CSMA and amino groups on SC. Meanwhile, because of the dynamic equilibrium of Schiff base linkage, the hydrogel was found to be self-healing. Cells encapsulated in the hydrogel remained viable and metabolically active. In addition, the hydrogel produced minimal inflammatory response when injected subcutaneously in a rat model and showed biodegradability in vivo. This work establishes an injectable and self-healing hydrogel derived from carbohydrates with potential applications as a cell carrier and in tissue engineering.

Recovery of ammonium onto wheat straw to be reused as a slow-release fertilizer.

With the aim of improving fertilizer use efficiency and minimizing the negative impact of nitrogen pollution, a new multifunctional slow-release fertilizer was prepared by recovery of ammonium from aqueous solutions onto a superabsorbent composite. An eco-friendly superabsorbent composite based on wheat straw (WS) was synthesized and used as the carrier to control the release of nutrients. The adsorption studies with NH4⁺ indicated that the superabsorbent composite showed good affinity for NH4⁺, with an adsorption capacity of 7.15 mmol g⁻¹ when 20 wt % of WS was incorporated and that the adsorption system can reach equilibrium within 40 min. Afterward, the feasibility of reusing the composite as a multifunctional slow-release nitrogen fertilizer was investigated. The results showed that the product with good water-retention and slow-release capacities could regulate soil acidity and was economical and eco-friendly for application in agriculture and horticulture.

A convenient way to synthesize comb-shaped chitosan-graft-poly (N-isopropylacrylamide) copolymer.

Comb-shaped copolymers comprised of hydrophobic and hydrophilic blocks are self-assembled in aqueous solution, which results that they are suitable for delivery of hydrophobic drug molecules. Chitosan (CS) is an important biomaterial used widely in medical applications. Herein, a comb-shaped cationic copolymer composed of long biocompatible CS main chains and short PNIPAAm side chains was prepared via atom transfer radical polymerization (ATRP) by attaching an ATRP initiating group to N-phthaloyl chitosan. By subsequent removal of the protective groups on N-phthaloyl chitosan-graft-poly(N-isopropylacrylamide) (PHCS-g-PNIPAAm) copolymer with N(2)H(4)·H(2)O lead to the polymer pendant amino groups, this study attempted to synthesize a pH/temperature multi-responsive material. This chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) copolymer is self-assembled in aqueous solution into stimuli-responsive core-shell micelles with hydrodynamic diameters of about 170 nm. Structural organization and solution behavior were then investigated utilizing (1)H NMR spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS).