Heparin-functionalized Cu-based metal-organic framework: An efficient active and passive targeting nanocarrier for anticancer doxorubicin drug delivery.

In this study, by innovative combining the unique characteristics of Cu-based metal-organic framework (MOF) with the versatile attributes of saccharides (i.e., heparin, Hep), a promising approach is established for active and passive targeting DDS, Cu-MOF/Hep, with a pH-controlled release profile and enhanced drug efficacy. The characterization of the synthesized materials (i.e., FT-IR, XRD, SEM, EDX, TEM, DLS, and TGA) confirms the successful synthesis of Cu-MOF/Hep. In vitro studies concerning the loading and release of DOX observed that a higher amount of DOX was released at pH 5 (>90 % on 96 h, 41 °C) compared to pH 7.4 (<10 % on 96 h, 37 °C). The sensitive feature of the used MOF to the pH conditions increased the drug release in environmental conditions similar to cancer tissues. Furthermore, cytotoxicity assessments indicated notable cytotoxicity effects of DOX-loaded Cu-MOF/Hep on MCF-7 cells (IC50: ∼10 µg/mL in 48 h) with a significant apoptosis rate. The existence of CD44 receptors on the surfaces of cells underscores the significance of Hep-modified systems in facilitating the apoptosis of cancerous cells. The results suggest that the combined Cu-MOF and Hep have the potential to be a viable option for creating platforms that deliver anticancer treatments.

Gelatin-based carbon quantum dot-molecularly imprinted polymer: Safe photoluminescent core-shell nano-carrier for the pH-responsive anticancer drug delivery.

This study aims to synthesize a core-shell gelatin-based carbon quantum dot-molecularly imprinted polymer (MIP@g-CQD) via the precipitation free-radical polymerization process using methotrexate (MTX) as a model anticancer template. To investigate the efficiency of the prepared photoluminescent MIP@g-CQD as a pH-responsive nano-carrier, MTX was loaded into MIP@g-CQD by soaking in a drug solution and the release behavior of the loaded drug was evaluated in the necessary pH values (7.4, 5). The successful synthesis of materials was characterized using PL, TEM, FE-SEM, DLS, and FT-IR analyses. Interestingly, the created cavities in the core-shell nano-carriers can interact with the MTX molecules effectively, leading to an increase in the loading capacity. According to the obtained results from Langmuir adsorption isotherms, the imprinting factor was calculated (IF = 4.91). Also, the binding kinetics of MTX revealed the creation of particular recognition sites in the core-shell polymeric network. The MTX-loaded MIP@g-CQD displayed a low rate and limited release at the simulated physiological environment (pH 7.4, 37 °C), but it is increased at tumor tissue (pH 5, 41 °C) conditions, which can lead to long-term and sustained release of MTX in the desired target. This property of MIP@g-CQD could avoid the release of MTX in normal physiological conditions, decreasing the possible side effects of MTX drug. Owing to the existence of amide functional groups in the nano-carrier structure and its negatively charged nature, the MTT assay displayed desirable cytotoxicity against the breast cancer cell line (MCF-7) for the MTX-loaded nano-carrier. According to the obtained results, the prepared safe photoluminescent MIP@g-CQD with appropriate pH-responsivity has a high ability to be applied as an anticancer and bio-detection agent.

Ultrasound-assisted encapsulating folic acid-based carbon quantum dots within breast cancer cell-derived exosomes as a co-receptors-mediated anticancer nanocarrier for enhanced breast cancer therapy.

The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer.

Incorporating mannose-functionalized hydroxyapatite/metal-organic framework into the hyaluronic acid hydrogel film: A potential dual-targeted oral anticancer delivery system.

The recent challenge in enhancing the targeted delivery of anticancer drugs to cancer cells is improving the bioavailability and therapeutic efficacy of drug delivery systems while minimizing their systemic side effects. In this study, the MIL-88(Fe) metal-organic framework was synthesized using the in situ method in the presence of hydroxyapatite nanoparticles (HAP) toward the HAP/MIL-88(Fe) (HM) nanocomposite preparation. It was then functionalized with mannose (M) as an anticancer receptor through the Steglich esterification method. Various analyses confirmed the successful synthesis of MHM. For drug release investigation, 5-Fu was loaded into the MHM, which was then coated with a hyaluronic acid (HA) hydrogel film. Characterization analyses verified the structure of the resulting HA/5-Fu-MHM hydrogel film. In vitro drug release experiments showed that the release of 5-Fu drug from HA/5-Fu-MHM could be controlled with pH, reducing its release rate in the acidic environment of the stomach while increasing it in the intestinal environment. Cytotoxicity results of the HA/5-Fu-MHM hydrogel film against HT29 cancer cells showed enhanced cytotoxicity due to the mannose and hyaluronic acid in its structure, which triggers a dual-targeted drug delivery system. The obtained results indicate that the prepared hydrogel films can be a promising bio-platform for colon cancer treatment.

Synthesis of MIL-88(Fe) coordinated to carboxymethyl cellulose fibers nanocomposite for dispersive solid phase microextraction of acetanilide herbicides from cereal and agricultural soil samples.

In this study, MIL-88(Fe) coordinated to carboxymethyl cellulose fibers was successfully synthesized, characterized, and utilized as a nanocomposite for the dispersive solid phase microextraction of butachlor and acetochlor. These analytes served as representative analytes for acetanilide herbicides (AHs) present in real samples. Effective parameters on the extraction efficiency were investigated to maximize the analytical performance of the developed method. Under optimized conditions, which encompassed sorbent amount of 12 mg, solution pH of 7.0, 4.0 min of the vortex time, 3.0 min of the extraction time, chloroform as desorption agent and no salt addition, the developed method exhibited remarkable figures of merit, such as high linearity (R2> 0.99), low limits of detection of 0.90 ng mL-1, substantial preconcentration factors (between 213 and 228), relative recoveries in the range of 90.8% to 109%, and good repeatability with relative standard deviations equal or below 7.2%. After validation, the developed method was applied to detect AHs in various cereal and agricultural soil samples.

Magnetic nanocomposite through coating mannose-functionalized metal-organic framework with biopolymeric pectin hydrogel beads: A potential targeted anticancer oral delivery system.

This study designed magnetic nanocomposite hydrogel beads for a potential targeted anticancer oral delivery system. To end this, nanohybrids of Fe3O4/MIL-88(Fe) (FM) were synthesized through in-situ method by the treatment of terephthalic acid (TPA) and (Fe(NO3)3·9H2O) in the presence of Fe3O4 nanoparticles. They were then modified with mannose sugar as an anticancer receptor to achieve a targeted drug delivery system. After loading methotrexate (MTX), they were coated with pH-sensitive pectin hydrogel beads in the presence of a calcium chloride crosslinker for possible transferring the nanohybrids to the intestine through the acidic environment of the digestive system. The results of different analysis techniques showed that the materials were properly synthesized, coated, and loaded. The designed magnetic nanocomposite hydrogel beads showed pH-sensitive swelling and drug release rate, protecting MTX from the acidic environment of the stomach. MTT test revealed a good cytotoxicity toward colon cancer HT29 cell lines. Remarkably, the functionalization of MTX-loaded FM nanohybrids with mannose (MTX-MFM) enhanced their anticancer properties up to about 20 %. The results recommended that the prepared novel magnetic nanocomposite hydrogel beads have a good potential to be used as a targeted anticancer oral delivery system.

In-situ green synthesis of copper tannic acid framework in the presence of graphene quantum dots: Improved colloidal and antibacterial properties.

This work reports the preparation of a copper tannic acid MOF (CuTA) and graphene quantum dot (GQD) nanocomposite, GQD/CuTA, by a simple, environmentally friendly, and inexpensive method with exceptionally enhanced antibacterial properties. To end this, GQDs were first fabricated from citric acid using a neoteric, simple and straightforward hydrolysis approach and followed by they effectively anchor MOF nanoparticles (CuTA) by a green hydrothermal in situ synthesizing method. The constructed GQD/CuTA nanomaterials were characterized and validated using XRD, FT-IR, TEM, DLS, UV-vis, and PL techniques. Significant antibacterial activity against E. coli bacteria for both CuTA and GQD/CuTA (0 CFU/mL) and S. aureus bacteria for CuTA and GQD/CuTA (300 and 40 CFU/mL) was observed for the GQD/CuTA nanocomposite. The MTT assay showed good cytocompatibility for the GQD/CuTA nanocomposite against human dermal fibroblast cells (HFF-2). The result suggests that the synthesized GQD/CuTA nanocomposite with improved colloidal and antibacterial properties has the potential to be used as a safe photoluminescent nanoplatform with strong antimicrobial activity.

Cyclodextrin Host-Guest Recognition in Glucose-Monitoring Sensors.

Diabetes mellitus is a prevalent chronic health condition that has caused millions of deaths worldwide. Monitoring blood glucose levels is crucial in diabetes management, aiding in clinical decision making and reducing the incidence of hypoglycemic episodes, thereby decreasing morbidity and mortality rates. Despite advancements in glucose monitoring (GM), the development of noninvasive, rapid, accurate, sensitive, selective, and stable systems for continuous monitoring remains a challenge. Addressing these challenges is critical to improving the clinical utility of GM technologies in diabetes management. In this concept, cyclodextrins (CDs) can be instrumental in the development of GM systems due to their high supramolecular recognition capabilities based on the host-guest interaction. The introduction of CDs into GM systems not only impacts the sensitivity, selectivity, and detection limit of the monitoring process but also improves biocompatibility and stability. These findings motivated the current review to provide a comprehensive summary of CD-based blood glucose sensors and their chemistry of glucose detection, efficiency, and accuracy. We categorize CD-based sensors into four groups based on their modification strategies, including CD-modified boronic acid, CD-modified mediators, CD-modified nanoparticles, and CD-modified functionalized polymers. These findings shed light on the potential of CD-based sensors as a promising tool for continuous GM in diabetes mellitus management.

Cellulose-based nanocomposite for ultrasonic assisted dispersive solid phase microextraction of triazole fungicides from water, fruits, and vegetables samples.

Herein, an ultrasound-assisted dispersive solid phase microextraction (UA-DSPME) approach has been described for trace level analysis of triazole fungicides in real samples. For this purpose, a new nanosorbent was prepared through modification of carboxymethylcellulose biopolymer with zinc-based metal-organic framework and graphene oxide, and fully characterized. Then, the effect of extraction parameters on extraction efficiency was optimized for the microextraction process. Finally, desorbed triazole fungicides with ethanol were determined using gas chromatography equipped with flame ionization detector. This technique provided good linearity (R2 > 0.99), low detection limits (0.3-1.5 ng mL-1), high preconcentration factors (419-426), good relative recoveries (91.6-102 %), and high repeatability (RSD < 4.1 %) at optimized conditions (amount of sorbent: 15 mg; pH of solution: 7.0; and extraction time; 4 min). Ultimately, this approach was applied to determine triazole fungicides in different water and food samples.

Gentamicin-loaded chitosan/folic acid-based carbon quantum dots nanocomposite hydrogel films as potential antimicrobial wound dressing.

BACKGROUND: To provide effective healing in the wound, various carbohydrate polymers are commonly utilized that are highly potent platforms as wound dressing films. In this work, novel antibacterial flexible polymeric hydrogel films were designed via crosslinking polymeric chitosan (CS) with folic acid-based carbon quantum dots (CQDs). To end this, folic acid as a bio-precursor is used to synthesize CQDs through the hydrothermal technique. The synthesized CQDs as a crosslinking agent was performed at different concentrations to construct nanocomposite hydrogel films via the casting technique. Also, gentamicin (GM), L-Arginine and glycerol were supplemented in the formulation of nanocomposite since their antibiotic, bioactivity and plasticizing ability, respectively. RESULTS: The successful construction of films were verified with different methods (FT-IR, UV-Vis, PL, SEM, and AFM analyses). The GM release profile displayed a controlled release manner over 48 h with a low initial burst release in the simulated wound media (PBS, pH 7.4). Antibacterial and in vitro cytotoxicity results showed a significant activity toward different gram-positive and negative bacterial strains (about 2.5 ± 0.1 cm inhibition zones) and a desired cytocompatibility against Human skin fibroblast (HFF-1) cells (over 80% cell viability), respectively. CONCLUSION: The obtained results recommend CQDs-crosslinked CS (CS/CQD) nanocomposite as a potent antimicrobial wound dressing.

Isocyanide-Based Multicomponent Reactions in Water: Advanced Green Tools for the Synthesis of Heterocyclic Compounds.

Reaction rate acceleration using green methods is an intriguing area of research for chemists. In this regard, water as a "green solvent" plays a crucial role in the acceleration of some organic transformations and reveals exclusive selectivity and reactivity in comparison with conventional organic solvents. In particular, multicomponent reactions (MCRs) as sustainable tools lead to the rapid generation of small-molecule libraries in water and aqueous media due to the prominent role of the hydrophobic effect. MCRs, as diversity-oriented synthesis (DOS) methods, have great efficiency with simple operations, atom, pot, and step economy synthesis, and mechanistic beauty. Among diverse classes of MCRs, isocyanide-based multicomponent reactions (I-MCRs), as sustainable and versatile reactions, have gained considerable attention in the synthesis of diverse heterocycle rings, especially in drug design because of the peculiar nature of isocyanide as a particular active reactant. I-MCRs that are performed in water are mild, environmentally friendly, and easily controlled, and have a reduced number of workup, purification, and extraction steps, which fit well with the advantages of "green" chemistry. Performing these powerful organic transformations in water and aqueous media is accompanied by acceleration owing to negative activation volumes, which originate from connecting several reactants together to generate a single product. It should be noted that the combination of MCR strategy and aqueous phase reaction is of growing interest for the development of sustainable synthetic techniques in organic conversions. However, an exclusive account focusing on the recent progress in eco-friendly I-MCRs for the construction of heterocycles in water and aqueous media is particularly lacking. This review highlights the progress of various kinds of I-MCRs in water and aqueous media as benign methods for the efficient construction of vital heterocyclic scaffolds, with a critical discussion of the subject in the period 2000-2021. We hope that this themed collection will be of interest and beneficial for organic and pharmaceutical chemists and will inspire more reaction development in this fascinating field.

Electrospun nanofibers based on carboxymethyl cellulose/polyvinyl alcohol as a potential antimicrobial wound dressing.

In this work, citric acid-based quantum dots (CA-QDs) as a novel and safe crosslinked agent was applied in different feeding ratios (5-15 wt%) to synthesize carboxymethyl cellulose/polyvinyl alcohol (CMC/PVA) nanofibers (NFs) for the first time. Colistin (CL) as an antibacterial agent was also loaded (2 w/w%) during the synthesizing process of CMC/PVA electrospun NFs to trigger antimicrobial properties. The morphological, hydrophilic, and mechanical properties of the prepared NFs were fully investigated with different techniques. The electrospun NFs with crosslinking ratios of 10 wt% CA-QDs revealed appropriate mechanical properties. According to cell culture data, the prepared NFs demonstrated good cytocompatibility against HFF-1 cells (over 80% cell viability). Remarkably, CL-loaded NFs showed desired antibacterial efficacy against S. aureus, E. coli, K. pneumoniae, and P. aeruginosa with 1.0-1.4, 1.3-1.4, 0.8-1.0, and 1.3-1.5 cm inhibition zones, respectively. These outcomes suggested that the fabricated NFs can be useful as wound healing scaffolds.

Copper phthalocyanine-conjugated pectin via the Ugi four-component reaction: An efficient catalyst for CO2 fixation.

Due to the cost-effectivity and biodegradability advantages of pectin, this type of polysaccharide attracted the attention of many researchers for catalyst construction. Accordingly, pectin was used as a green support in this study to construct an efficient heterogeneous catalytic system based on the conjugation of metal phthalocyanines. To end this, pectin was first oxidized with periodate oxidant agent to effectively immobilize a tetra-amino copper phthalocyanine (Cu-PcTA) through a green, simple, and an efficient one-pot Ugi four-component reaction (Ugi-4CR). Then, the catalytic activity of the copper phthalocyanine-conjugated pectin was investigated in the CO2 fixation reaction to cyclic carbonates. Optimum catalytic conditions were as follows: 30 mg of prepared catalyst, 3 bar CO2 pressure, 90 °C, 2 h, and TBAB as a co-catalyst. Pectin can successfully improve the catalytical properties of the Cu-PcTA over the CO2 fixation reaction.

Application or function of citric acid in drug delivery platforms.

Nontoxic materials with natural origin are promising materials in the designing and preparation of the new drug delivery systems (DDSs). Today's, citric acid (CA) has attracted a great deal of attention because of its special features; green nature, biocompatibility, low price, biodegradability, and commercially available property. So, CA has been employed in the preparation of the various platforms to induce a suitable property on their structure. Recently, several research groups investigated the CA-based platforms in different forms like tablets, dendrimers, hyperbranched polymers, (co)polymer, hydrogels, and nanoparticles as efficient DDSs. By considering an increasing amount of published articles in this field, for the first time, in this review, an overview of the published works regarding CA applications in the design of various DDSs is presented with a detailed and insightful discussion.

Facile synthesis of Zn-based metal-organic framework in the presence of carboxymethyl cellulose: A safe carrier for ibuprofen.

Fabrication of porous materials with a high surface area affords a great interest to achieve a system with a prolonged drug release manner. In this context, the subject of this work is to describe a novel green one-pot synthesis route for the growth of metal-organic framework (MOF) from zinc metal (Zn) and 1, 4-benzene dicarboxylic acid (BDC) in the vicinity of the carboxymethyl cellulose (CMC), which homogeneously confined in the biopolymeric chains. The synthesized Zn (BDC)@CMC was characterized and confirmed using different analyses. N2 adsorption/desorption isotherms determined the mean diameter of pore size of about 2.3993 nm. Ibuprofen (IBU) as a model drug was highly loaded to the Zn(BDC)@CMC by immersing in the drug solution; 50.95%. The in vitro IBU release study indicated that the Zn(BDC)@CMC has more attractive performances than pristine Zn(BDC). The IBU release occurred via the Fickian mechanism. Isotherm studies showed that the IBU adsorption on obeys from Langmuir isotherm; R2 0.9623. The MTT results revealed the HEK 293A cell viability of higher than 90% for Zn(BDC)@CMC that confirms its cytocompatibility. Overall, obtained results confirm the functionality of CMC biopolymer for in situ growth of MOF in the presence of it due to having the reactive nature.

Carboxymethyl cellulose/tetracycline@UiO-66 nanocomposite hydrogel films as a potential antibacterial wound dressing.

Designing an antibacterial agent with a suitable water vapor permeability, good mechanical properties, and controlled antibiotic release is a promising method for stopping bacterial infection in wound tissue. In this respect, this work aims to prepare novel flexible polymeric hydrogel films via integrating UiO-66 into the polymeric carboxymethyl cellulose (CMC) hydrogel for improving the mechanical and antibiotic release performances. First, we performed a green hydrothermal synthetic method to synthesis UiO-66 and followed by encapsulating Tetracycline (TC) through immersion in its aqueous solution. Also, the casting technique was utilized to integrate different concentrations of the TC-encapsulated UiO-66 (TC@UiO-66, 5% to 15%) in the polymeric CMC matrix (CMC/TC@UiO-66) cross-linked by citric acid and plasticized by glycerol. The release performance showed a low initial burst release with a controlled release over 72 h in the artificial sweat and simulated wound exudate (PBS, pH 7.4) media. The in vitro cytotoxicity and antibacterial activity results revealed a good cytocompatibility toward Human skin fibroblast (HFF-1) cells and a significant activity against both E. coli and S. aureus with 1.3 and 1.7 cm inhibition zone, respectively. The obtained results recommend CMC/TC@UiO-66 films as a potential antibacterial wound dressing.

Cu-decorated cellulose through a three-component Betti reaction: An efficient catalytic system for the synthesis of 1,3,4-oxadiazoles via imine CH functionalization of N-acylhydrazones.

Materials functionalization through multicomponent reactions (MCRs) has recently attracted great attention due to the generation of outstanding features in materials. Herein, an efficient novel heterogeneous catalytic system was designed and synthesized via the MCRs functionalization of the most abundant biopolymer in nature, cellulose. In this regard, cellulose was oxidized using periodate as an oxidant agent, and then the resulted carbonyl functional groups participated in the three-component Betti reaction. The ICP-OES analysis was revealed that the functionalization of cellulose via this three-component reaction effectively improved the complexing ability of functionalized cellulose with Cu(II). The synthesized biocatalyst was characterized by FT-IR, 1H NMR, XRD, SEM, EDS, ICP, and TGA techniques. The efficiency of the designed biocatalyst was investigated in the CH functionalization reaction of N-acylhydrazones to synthesize 1,3,4-oxadiazoles. This biocatalyst's outstanding advantages are high yields, non-hazardous catalyst, mild reaction conditions, operational simplicity, and reusability.

Nanoscale Metal-Organic Frameworks: Recent developments in synthesis, modifications and bioimaging applications.

Porous Metal-Organic Frameworks (MOFs) have emerged as eye-catching materials in recent years. They are widely used in numerous fields of chemistry thanks to their desirable properties. MOFs have a key role in the development of bioimaging platforms that are hopefully expected to effectually pave the way for accurate and selective detection and diagnosis of abnormalities. Recently, many types of MOFs have been employed for detection of RNA, DNA, enzyme activity and small-biomolecules, as well as for magnetic resonance imaging (MRI) and computed tomography (CT), which are valuable methods for clinical analysis. The optimal performance of the MOF in the bio-imaging field depends on the core structure, synthesis method and modifications processes. In this review, we have attempted to present crucial parameters for designing and achieving an efficient MOF as bioimaging platforms, and provide a roadmap for researchers in this field. Moreover, the influence of modifications/fractionalizations on MOFs performance has been thoroughly discussed and challenging problems have been extensively addressed. Consideration is mainly focused on the principal concepts and applications that have been achieved to modify and synthesize advanced MOFs for future applications.

Ultrasound-assisted synthesis of MIL-88(Fe) coordinated to carboxymethyl cellulose fibers: A safe carrier for highly sustained release of tetracycline.

For stopping long-time harmful bacterial infection, designing a drug carrier with a highly prolonged release profile is a promising approach that is of interest to different biomedical areas. The subject of this work is to synthesis a novel carrier system through coordination of MIL-88(Fe) to carboxymethyl cellulose (CMC) for enhancing interaction between drug and carrier. We established an ultrasound-assisted synthetic method for in situ synthesis of MIL-88(Fe) in the presence of CMC resulting in CMC/MIL-88(Fe) composite. The CMC/MIL-88(Fe) was loaded with a high amount of Tetracycline (TC) by immersion of carrier to the TC aqueous solution. The release profile in the simulated physiological conditions, pH 7.4, revealed a low initial burst release followed by a sustained and prolonged release over 384 h. The in vitro cytotoxicity of CMC/MIL-88(Fe) against Human skin fibroblast (HFF-1) cells was calculated by MTT assay and showed a good cytocompatibility. The antibacterial activity was found for TC-loaded CMC/MIL-88(Fe) toward both E. coli and S. aureus with MIC 64 mg·ml-1.