pH-sensitive biosystem based on laponite RD/chitosan/polyvinyl alcohol hydrogels for controlled delivery of curcumin to breast cancer cells.

In this study, a pH-responsive hydrogels based on laponite rapid dispersion (Lap®)/chitosan (CS)/polyvinyl alcohol (PVA) designed and was used for controlled delivery of the anticancer drug curcumin (CUR). First, it was accomplished by dissolving CUR in Lap® dispersion under the influence of the pH of the environment. Then, in the presence of Lap®CUR cross-linking was incorporated between CS and PVA polymers. The structural features of Lap®CUR/CS@PVA hydrogels are characterized using FT-IR, XRD, SEM/EDS, TEM, TGA, Zeta potential, and XPS. The in vitro drug release profiles confirmed a pH-responsive controlled release of CUR in acidic pH for all hydrogels. During 12 h, the cumulative release of CUR from Lap®CUR/0.1CS@PVA hydrogel was 27.9% and 12.3%, at pH 5.5 and 7.4, respectively. While during three days the release rate reached 48.5% and 18.5%. The CUR release kinetic from hydrogels also suggests that the kinetic data well fitted to the Korsmeyer-Peppas, diffusion-controlled and Fickian diffusion. Furthermore, in vitro cytotoxicity and DAPI staining study clearly illustrated that Lap®CUR/0.1CS@PVA hydrogel had lower cytotoxicity than CUR against MDA-MB 231 cancer cells, which confirmed the controlled release of drug through hydrogels. Meanwhile, in vitro hemolysis, antioxidant and antibacterial tests revealed that the prepared hydrogels have good blood compatibility, excellent antioxidant properties, and antibacterial activity. Based on the obtained results, the designed hydrogels could be potentially applied as pH-controlled drug delivery systems for cancer therapy.

Foliar application of chitosan-putrescine nanoparticles (CTS-Put NPs) alleviates cadmium toxicity in grapevine (Vitis vinifera L.) cv. Sultana: modulation of antioxidant and photosynthetic status.

BACKGROUND: Cadmium (Cd) stress displays critical damage to the plant growth and health. Uptake and accumulation of Cd in plant tissues cause detrimental effects on crop productivity and ultimately impose threats to human beings. For this reason, a quite number of attempts have been made to buffer the adverse effects or to reduce the uptake of Cd. Of those strategies, the application of functionalized nanoparticles has lately attracted increasing attention. Former reports clearly noted that putrescine (Put) displayed promising effects on alleviating different stress conditions like Cd and similarly chitosan (CTS), as well as its nano form, demonstrated parallel properties in this regard besides acting as a carrier for many loads with different applications in the agriculture industry. Herein, we, for the first time, assayed the potential effects of nano-conjugate form of Put and CTS (CTS-Put NP) on grapevine (Vitis vinifera L.) cv. Sultana suffering from Cd stress. We hypothesized that their nano conjugate combination (CTS-Put NPs) could potentially enhance Put proficiency, above all at lower doses under stress conditions via CTS as a carrier for Put. In this regard, Put (50 mg L- 1), CTS (0.5%), Put 50 mg L- 1 + CTS 0.5%" and CTS-Put NPs (0.1 and 0.5%) were applied on grapevines under Cd-stress conditions (0 and 10 mg kg- 1). The interactive effects of CTS-Put NP were investigated through a series of physiological and biochemical assays. RESULTS: The findings of present study clearly revealed that CTS-Put NPs as optimal treatments alleviated adverse effects of Cd-stress condition by enhancing chlorophyll (chl) a, b, carotenoids, Fv/Fm, Y(II), proline, total phenolic compounds, anthocyanins, antioxidant enzymatic activities and decreasing Y (NO), leaf and root Cd content, EL, MDA and H2O2. CONCLUSIONS: In conclusion, CTS-Put NPs could be applied as a stress protection treatment on plants under diverse heavy metal toxicity conditions to promote plant health, potentially highlighting new avenues for sustainable crop production in the agricultural sector under the threat of climate change.

pH-responsive magnetic biocompatible chitosan-based nanocomposite carrier for ciprofloxacin release.

The pH-sensitive and magnetic-triggered release ensures the effective delivery of drugs. Chitosan carries amine pendants that encourage the fabrication of pH-responsive carriers. Montmorillonite (MMt), an attractive nano-clay in drug delivery possessing high encapsulation properties, was magnetized through the co-precipitation of Fe3+/Fe2+ ions. The study aimed to integrate the magnetic montmorillonite (mMMt) into the chitosan matrix and crosslinked by citric acid (CA) to achieve the nanocomposite carrier with double-responsive features for effective drug delivery. The release evaluation revealed that coating the mMMt with CA-crosslinked chitosan prevented the burst release of Ciprofluxcacin (Cip). The nanocomposite showed a high sustained release, and the release rate in the neutral environment (pH 7.4) was remarkably higher than in acidic media (pH 5.8). The new nanocomposite carrier showed high encapsulation efficiency to Cip (about 98 %). The study was developed by investigating external magnetic effects on the release rate, which lead to an increase in the release rate. The kinetics studies confirmed the diffusion mechanism for Cip release in all experimental media. The Cip-loaded nanocomposite carriers showed antibacterial activity against E. coli and S. aureus.

Cellulose nanofibers decorated with SiO2 nanoparticles: Green adsorbents for removal of cationic and anionic dyes; kinetics, isotherms, and thermodynamic studies.

Cellulose nanofibers decorated with SiO2 nanoparticles (SiO2-CNF) were prepared by the extraction of cellulose nanofibers from Yucca leaves, followed by modification with SiO2 nanoparticles, and used as efficient materials for the removal of both anionic and cationic dyes from the aqueous solution. Prepared nanostructures were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction powder (XRD), Thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and transmission electron microscopy (TEM) analysis. The adsorption capacity of the nanostructures was investigated for the removal of both cationic (Methylene Blue, MB, and Crystal Violet, CV) and anionic (Eriochrome Black-T, EB) dyes. The kinetics of adsorption were investigated using some well-known models, including intraparticular diffusion (IPD), pseudo-first-order (PFO), pseudo-second-order (PSO), and Elovich. The adsorption isotherms were also explored using the Langmuir, Freundlich, Temkin, and Redlich-Peterson models. The obtained results revealed that the adsorption processes follow PSO kinetic and Langmuir isotherm models. Thermodynamic parameters of the adsorption were measured at different temperatures, indicating the feasibility and spontaneity of the adsorption. The pH and salt effects on adsorption were also explored. Finally, according to the reusability tests, the prepared adsorbents showed high recoverability without considerable loss in adsorption efficiency after five repeated runs.

pH-sensitive biocompatible chitosan/sepiolite-based cross-linked citric acid magnetic nanocarrier for efficient sunitinib release.

In this study, the magnetite nanoparticles were immobilized on the sepiolite needles via co-precipitation of iron ions. Then, the resulted magnetic sepiolite (mSep) nanoparticles were coated with chitosan biopolymer (Chito) in the presence of citric acid (CA) to prepare mSep@Chito core-shell drug nanocarriers (NCs). TEM images showed magnetic Fe3O4 nanoparticles with small sizes (less than 25 nm) on the sepiolite needles. Sunitinib anticancer drug loading efficiencies were ⁓45 and 83.7 % for the NCs with low and high content of Chito, respectively. The in-vitro drug release results exhibited that the mSep@Chito NCs have a sustained release behavior with high pH-dependent properties. Cytotoxic results (MTT assay) showed that the sunitinib-loaded mSep@Chito2 NC had a significant cytotoxic effect on the MCF-7 cell lines. Also, the in-vitro compatibility of erythrocytes, physiological stability, biodegradability, and antibacterial and antioxidant activities of NCs was evaluated. The results showed that the synthesized NCs had excellent hemocompatibility, good antioxidant properties, and were sufficiently stable and biocompatible. Based on the antibacterial data, the minimal inhibitory concentration (MIC) values for mSep@Chito1, mSep@Chito2, and mSep@Chito3 were obtained as 125, 62.5, and 31.2 µg/mL towards S. aureus, respectively. All in all, the prepared NCs could be potentially used as a pH-triggered system for biomedical applications.

Putrescine-functionalized carbon quantum dot (put-CQD) nanoparticle: A promising stress-protecting agent against cadmium stress in grapevine (Vitis vinifera cv. Sultana).

Due to their sessile nature, plant cannot escape from stress factors in their growing environment, in either biotic or abiotic nature. Amid the abiotic stress factors; high levels of soil cadmium (Cd) impose heavy metal stress on plants, resulting in critical injuries and reduced agronomic performance. In order to buffer the adverse effects of Cd stress, novel nanoparticles (NP) have been applied and notable improvements have been reported. According to the literature, the protective roles of polyamines (e.g., Putrescine; Put) and carbon quantum dots (CQD) have been reported with respect to the plant productivity under either stress or non-stress conditions. Those reports led us to hypothesize that the conjugation of Put and CQD (Put-CQD NPs) might lead to further augmented performance of plants under stress and non-stress conditions. In this regard, we successfully synthesized a novel nanomaterial Put-CQD NPs. In this respect, Put (50 mg L-1), CQD (50 mg L-1) and Put-CQD NPs (25 and 50 mg L-1) were sprayed in 'Sultana' grapevines under Cd stress (10 mg kg-1). As expected, upon stress, Cd content in leaf and root tissues increased by 103.40% and 65.15%, respectively (p < 0.05). The high uptake and accumulation of Cd in plant tissues were manifested in significant alterations of physiological and biochemical attributes of the plant. Concerning stress markers, Cd stress caused increases in content of induced MDA, H2O2, and proline as well as electrolyte leakage rate. As expected, Cd stress caused critical reductions in fresh and dry leaf weight by 21.31% and 42.34%, respectively (p < 0.05). On the other hand, both Put-CQD NPs increased fresh and dry leaf weigh up to approximately 30%. The Cd-mediated disturbances in photosynthetic pigments and chlorophyll fluorescence were buffered with Put-CQD NPs. Of the defence system, enzymatic (SOD, APX, GP) as well as anthocyanin and phenolics were induced by both Cd stress and Put-CQD NPs (p < 0.05). On the other hand, Cd stress reduced content of polyamines (putrescine (Put), spermine (Spm) and spermidine (Spd) by 39.28%, 53.36%, and 39.26%, respectively (p < 0.05). However, the reduction levels were buffered by the treatments. Considering the effectiveness of both NP concentrations, the lower dose (25 mg L-1) could be considered as an optimal concentration. To our knowledge, this is the first report of its kind as a potential agent to reduce the adverse effects of Cd stress in grapevines.

Mitigation of salinity impact in spearmint plants through the application of engineered chitosan-melatonin nanoparticles.

High soil salinity represents a critical environmental constraint to crop production. In order to ameliorate the effects of salinity, a plethora of molecules have been applied and promising outcomes have been noted. The beneficial effects of chitosan (CTS) and melatonin (Mel) application, separately, have been previously recorded with respect to plant growth and productivity, leading to the hypothesis that their conjugation in the form of chitosan-melatonin nanoparticles (CTS-HPMC-Mel NPs) could lead to further enhanced performance of plants under control and stress conditions. In this regard, novel CTS-HPMC-Mel NPs were synthesized, characterized and then employed as a chemical priming agent in spearmint (Mentha spicata L.) plants 24 h prior to salinity stress imposition. As expected, salt stress negatively affected morphophysiological attributes such as plant height, leaf number, leaf fresh weight, leaf dry weight, photosynthetic pigments, Fv/Fo, and Fv/Fm. On the other hand, stress-related attributes, such as content of proline, MDA and H2O2, as well as activity of APX and GP enzymes were increased in response to salt stress. However, adverse effects of salt stress were ameliorated with Mel and CTS-HPMC-Mel NP treatments by enhancing morphological traits, proline, antioxidant enzymatic activities, as well as content of dominant constituents of essential oil profile. It is worth noting that conjugated form of Mel with chitosan, in comparison with solo treatment of Mel, was more effective in combating stress effects. To our knowledge, this is the first report to demonstrate that engineered CTS-HPMC-Mel NPs could be applied as an innovative protective agent to mitigate the effects of salinity in crop plants.

Improving the Berry Quality and Antioxidant Potential of Flame Seedless Grapes by Foliar Application of Chitosan-Phenylalanine Nanocomposites (CS-Phe NCs).

The production and sustainability of grape berries with high quality and health-promoting properties is a major goal. In this regard, nano-engineered materials are being used for improving the quality and marketability of berries. In this study, we investigated the potential role of chitosan-phenylalanine nanocomposites (CS-Phe NCs) in improving the quality of Flame Seedless (Vitis vinifera L.) grape berries, such as titratable acidity (TA), pH, total soluble solids (TSS), ascorbic acid, total phenolics, total flavonoids, anthocyanin, 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity, and phenylalanine ammonia-lyase (PAL) activity. In this context, grape berries collected in two growing seasons (2018-2019) were screened. Regarding the experimental design, the treatments included chitosan at a 0.5% concentration (CS 0.5%), phenylalanine at 5 mM and 10 mM concentrations (Phe 5 mM and Phe 10 mM), and chitosan-phenylalanine nanocomposites (CS-Phe NCs) at 5 mM and 10 mM concentrations. The lowest TA was recorded in grape berries treated with CS-Phe NCs with a 10 mM concentration. However, treatments enhanced with TSS, which reached the highest value with 10 mM of CS-Phe NCs, were reflected as the highest ratio of TSS/TA with 10 mM of CS-Phe NC treatment. Nanocomposites (NCs) also increased pH values in both study years compared to the control. Similarly, the ascorbic acid and total phenolic content increased in response to NP treatment, reaching the highest value with 5 mM and 10 mM of CS-Phe NCs in 2018 and 2019, respectively. The highest flavonoid content was observed with 5 mM of CS-Phe NCs in both study years. In addition, the anthocyanin content increased with 5 and 10 mM of CS-Phe NCs. PAL activity was found to be the highest with 5 mM of CS-Phe NCs in both study years. In addition, in accordance with the increase in PAL activity, increased total phenolics and anthocyanin, and higher DPPH radical scavenging activity of the grapes were recorded with the treatments compared to the control. As deduced from the findings, the coating substantially influenced the metabolic pathway, and the subsequent alterations induced by the treatments were notably appreciated due to there being no adverse impacts perceived.

Adsorption of Cationic Dyes on a Magnetic 3D Spongin Scaffold with Nano-Sized Fe3O4 Cores.

The renewable, proteinaceous, marine biopolymer spongin is yet the focus of modern research. The preparation of a magnetic three-dimensional (3D) spongin scaffold with nano-sized Fe3O4 cores is reported here for the first time. The formation of this magnetic spongin-Fe3O4 composite was characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential thermal analysis (DTA) (TGA-DTA), vibrating sample magnetometer (VSM), Fourier-transform infrared spectroscopy (FTIR), and zeta potential analyses. Field emission scanning electron microscopy (FE-SEM) confirmed the formation of well-dispersed spherical nanoparticles tightly bound to the spongin scaffold. The magnetic spongin-Fe3O4 composite showed significant removal efficiency for two cationic dyes (i.e., crystal violet (CV) and methylene blue (MB)). Adsorption experiments revealed that the prepared material is a fast, high-capacity (77 mg/g), yet selective adsorbent for MB. This behavior was attributed to the creation of strong electrostatic interactions between the spongin-Fe3O4 and MB or CV, which was reflected by adsorption mechanism evaluations. The adsorption of MB and CV was found to be a function of pH, with maximum removal performance being observed over a wide pH range (pH = 5.5-11). In this work, we combined Fe3O4 nanoparticles and spongin scaffold properties into one unique composite, named magnetic spongin scaffold, in our attempt to create a sustainable absorbent for organic wastewater treatment. The appropriative mechanism of adsorption of the cationic dyes on a magnetic 3D spongin scaffold is proposed. Removal of organic dyes and other contaminants is essential to ensure healthy water and prevent various diseases. On the other hand, in many cases, dyes are used as models to demonstrate the adsorption properties of nanostructures. Due to the good absorption properties of magnetic spongin, it can be proposed as a green and uncomplicated adsorbent for the removal of different organic contaminants and, furthermore, as a carrier in drug delivery applications.

Salt Stress Mitigation via the Foliar Application of Chitosan-Functionalized Selenium and Anatase Titanium Dioxide Nanoparticles in Stevia (Stevia rebaudiana Bertoni).

High salt levels are one of the significant and major limiting factors on crop yield and productivity. Out of the available attempts made against high salt levels, engineered nanoparticles (NPs) have been widely employed and considered as effective strategies in this regard. Of these NPs, titanium dioxide nanoparticles (TiO2 NPs) and selenium functionalized using chitosan nanoparticles (Cs-Se NPs) were applied for a quite number of plants, but their potential roles for alleviating the adverse effects of salinity on stevia remains unclear. Stevia (Stevia rebaudiana Bertoni) is one of the reputed medicinal plants due to their diterpenoid steviol glycosides (stevioside and rebaudioside A). For this reason, the current study was designed to investigate the potential of TiO2 NPs (0, 100 and 200 mg L-1) and Cs-Se NPs (0, 10 and 20 mg L-1) to alleviate salt stress (0, 50 and 100 mM NaCl) in stevia. The findings of the study revealed that salinity decreased the growth and photosynthetic traits but resulted in substantial cell damage through increasing H2O2 and MDA content, as well as electrolyte leakage (EL). However, the application of TiO2 NPs (100 mg L-1) and Cs-Se NPs (20 mg L-1) increased the growth, photosynthetic performance and activity of antioxidant enzymes, and decreased the contents of H2O2, MDA and EL under the saline conditions. In addition to the enhanced growth and physiological performance of the plant, the essential oil content was also increased with the treatments of TiO2 (100 mg L-1) and Cs-Se NPs (20 mg L-1). In addition, the tested NPs treatments increased the concentration of stevioside (in the non-saline condition and under salinity stress) and rebaudioside A (under the salinity conditions) in stevia plants. Overall, the current findings suggest that especially 100 mg L-1 TiO2 NPs and 20 mg L-1 Cs-Se could be considered as promising agents in combating high levels of salinity in the case of stevia.

Magnetic κ-carrageenan/chitosan/montmorillonite nanocomposite hydrogels with controlled sunitinib release.

This work aimed to design montmorillonite-incorporated pH-responsive and magnetic κ-carrageenan/chitosan hydrogels via a completely green route for controlled release of sunitinib anticancer drug. This was accomplished by ionic cross-linking of two biopolymers, κ-carrageenan and chitosan, in the presence of magnetic montmorillonite (mMMt) nanoplatelets. Interestingly, it was observed that the amount of mMMt affected not only the microstructure of hydrogels, but also the drug loading efficiency of nanocomposite hydrogels was noticeably increased by introducing mMMt (from 69 to 96%). The in vitro sunitinib release experiments showed that a low content of loaded sunitinib was released from all hydrogels in the buffered solution with pH 7.4. In contrast, a relatively sustained release with a high content of drug release was observed in the acidic solution of pH 5.5. During 48 h, the hydrogels nanocomposite containing a high content of mMMt showed cumulative release of 64.0 and 8.6% at pH 5.5 and 7.4, respectively. During two days, while the cumulative release of sunitinib was obtained 84.3% for the magnetic-free hydrogel, the magnetic ones showed 74.4 and 64% with the low and high contents of magnetic MMt, respectively. The developed κ-carrageenan/chitosan hydrogels with a high capacity of drug loading and subsequent pH-sensitive drug release can be considered in prolonged cancer therapy with reduced side effects.

Enhanced tolerance to salinity stress in grapevine plants through application of carbon quantum dots functionalized by proline.

Salinity has destructive impacts in plant production; therefore, application of new approaches such as nanotechnology and plant priming is attracting increasing attention as an innovative means to ameliorate salt stress effects. Considering the unique properties and recorded beneficial influence of carbon quantum dots (CQDs) and proline in plant growth and physiological parameters when applied individually, their conjugation in the form of carbon quantum dot nanoparticles functionalized by proline (Pro-CQDs NPs) could lead to synergistic effects. Accordingly, an experiment was conducted to evaluate the impact of this advanced nanomaterial (Pro-CQDs NPs) as a chemical priming agent, in grapevine plants cv. 'Rasha'. For this purpose, proline, CQDs, and Pro-CQDs NPs at three concentrations (0, 50, and 100 mg L-1) were applied exogenously 48 h prior to salinity stress (0 and 100 mM NaCl) that was imposed for a month. Three days after imposing salt stress, an array of biochemical measurements was recorded, while agronomic and some physiological parameters were noted at the end of the stress period. Results revealed that proline treatment at both concentrations, as well as CQDs and Pro-CQDs NPs at low concentration, positively affected grapevine plants under both non-stress and stress conditions. Specifically, the application of proline at 100 mg L-1 and Pro-CQDs NPs at 50 mg L-1 resulted in optimal performance identifying 50 mg L-1 Pro-CQDs NPs as the optimal treatment. Proline treatment at 100 mg L-1 increased leaf fresh weight (FW) and dry weight (DW); chl a, b, and proline content; SOD activity under both non-stress and stress conditions; Y (II) under salinity and carotenoid content; and CAT activity under control conditions. Pro-CQDs NP treatment at 50 mg L-1 enhanced total phenol, anthocyanin, and Fv/Fo, as well as APX and GP activities under both conditions, while increasing carotenoid, Y (II), Fv/Fo, and CAT activity under salinity. Furthermore, it decreased MDA and H2O2 contents at both conditions and EL and Y (NO) under salt stress. Overall, conjugation of CQDs with proline at 50 mg L-1 resulted in further improving the protective effect of proline application at 100 mg L-1. Therefore, functionalization of NPs with chemical priming agents appears to be an effective means of optimizing plant-priming approaches towards efficient amelioration of abiotic stress-related damage in plants.

Highly efficient sunitinib release from pH-responsive mHPMC@Chitosan core-shell nanoparticles.

This study reports developing novel smart drug delivery systems (DDS) that have great importance in anticancer therapeutics. The magnetic hydroxypropyl methylcellulose (mHPMC) synthesized via in situ method and introduced in the fabrication of tripolyphosphate (TPP)-cross-linked chitosan core-shell nano-carriers (mHPMC@Chitosan). The TPP-cross-linked mHPMC@Chitosan nano-carriers then characterized using TEM, SEM/EDS, DLS, XPS, FTIR, TGA, XRD, and VSM. The encapsulation efficiency showed high capacity of loading for sunitinib malate (above 86 % for all samples). At pH 7.4, the minimum content of drug release was observed for all samples fabricated with variable contents of chitosan. At pH 4.5, the effect of chitosan content revealed that the rate of sunitinib release tends to decrease as its content increased. During two days, 44 and 93 % of the loaded sunitinib released from carriers containing high and low contents of chitosan, respectively. Besides, this mHPMC@Chitosan core shell nano-carrier shown pH-sensitive drug release.