Dimethylmaleic Anhydride Research Articles

Active-transporting of charge-reversal Cu(II)-doped mesoporous silica nanoagents for antitumor chemo/chemodynamic therapy

Fe-based Fenton agents can generate highly reactive and toxic hydroxyl radicals (·OH) in the tumor microenvironment (TME) for chemodynamic therapy (CDT) with high specificity. However, the low pH environment and insufficient endogenous hydrogen peroxide (H2O2) of the highly efficient Fenton reaction limits its practical application in clinic. Here, a Cu(II)-doped mesoporous silica nanoagent (Cu-MSN) with excellent dispersity was successfully developed. After loaded with doxorubicin (DOX) and ascorbate (AA), Cu-MSN@DA was coated with active targeting ligand folic acid (FA), dimethyl maleic an-hydride (DMMA) and carboxymethyl chitosan (CMC) to obtain an active transporting nanoagent (FCDC@Cu-MSN@DA) with tunable charge-reversal property, which is more adaptable to the pH value of TME than Fe-based Fenton agents, and can self-supply exogenous H2O2 by ascorbate to produce more toxic ·OH to trigger the apoptosis of cancer cells. Meanwhile, the high level of glutathione (GSH) in TME can reduce Cu(II) to Cu(I) by Fenton-like reaction, increasing the generation rate of ·OH and relieving tumor antioxidant ability. The supply of exogenous H2O2 significantly enhanced the synergistic effect of CDT by oxidative damage. Together with DOX-induced cell apoptosis, this novel nanoagent FCDC@Cu-MSN@DA can achieve maximum therapeutic efficacy, creating a new model of safe and effective tumor treatment with high specificity.

Microenvironment responsive charge-switchable nanoparticles act on biofilm eradication and virulence inhibition for chronic lung infection treatment

Chronic pulmonary infection caused by Pseudomonas aeruginosa (P. aeruginosa) is a common lung disease with high mortality, posing severe threats to public health. Highly resistant biofilm and intrinsic resistance make P. aeruginosa hard to eradicate, while powerful virulence system of P. aeruginosa may give rise to the recurrence of infection and eventual failure of antibiotic therapy. To address these issues, infection-microenvironment responsive nanoparticles functioning on biofilm eradication and virulence inhibition were simply prepared by electrostatic complexation between dimethylmaleic anhydride (DA) modified negatively charged coating and epsilon-poly(l-lysine) derived cationic nanoparticles loaded with azithromycin (AZI) (DA-AZI NPs). Charge reversal responsive to acidic condition enabled DA-AZI NPs to successively penetrate through both mucus and biofilms, followed by targeting to P. aeruginosa and permeabilizing its outer/inner membrane. Then in situ released AZI, which was induced by the lipase-triggered NPs dissociation, could easily enter into bacteria to take effects. DA-AZI NPs exhibited enhanced eradication activity against P. aeruginosa biofilms with a decrease of >99.999% of bacterial colonies, as well as remarkable inhibitory effects on the production of virulence factors and bacteria re-adhesion & biofilm re-formation. In a chronic pulmonary infection model, nebulization of DA-AZI NPs into infected mice resulted in prolonged retention and increased accumulation of the NPs in the infected sites of the lungs. Moreover, they significantly reduced the burden of P. aeruginosa, effectively alleviating lung tissue damages and inflammation. Overall, the proposed DA-AZI NPs highlight an innovative strategy for treating chronic pulmonary infection.

Cuproptosis‐Driven Enhancement of Thermotherapy by Sequentially Response Cu2‐xSe via Copper Chemical Transition

AbstractActivation of cuproptosis pathway has been reported to hold great potential in the application of tumor treatment. But the efficacy of cuproptosis seriously limited by the insufficient accumulation in the tumor sites. Therefore, herein based on the strong stabilization effects of the metalloid element selenium (Se) on copper (Cu), a photothermic Cu2‐xSe nanoparticle encapsulated with bioresponsive dimethyl maleic anhydride (DMMA@Cu2‐xSe) as a copper‐carrier to improve the copper accumulation in tumor is constructed, thus achieving cuproptosis‐driven enhancement of thermotherapy. This nanosystem exhibits the enhancement of tumor cellular uptake by a weak acid‐triggered charge‐switching ability. Next step, the exposed Cu2‐xSe is oxidized and releases divalent copper by high‐level oxide. Then, the abundant copper induces more dihydrolipoamide S‐acetyltransferase oligomerization to down‐regulate FDX1 and tricarboxylic acid cycle‐related proteins, which leads to inhibiting aerobic respiration. Cuproptosis‐induced mitochondrial damage further improves thermotherapy by up‐regulating reactive oxygen species (ROS). In addition, the generated ROS also promotes copper release to strengthen cuproptosis, and eventually improves tumor thermotherapy in turn. In general, DMMA@Cu2‐xSe with sequentially triggered copper‐release, efficient cuproptosis, and appropriate photothermal is a self‐enhanced nanoplatform for cuproptosis‐driven enhancement of thermotherapy.

Dual size/charge-switchable and multi-responsive gelatin-based nanocluster for targeted anti-tumor therapy

Biopolymers with excellent biocompatibility and biodegradability show great potential for designing drug nanocarriers, while it's difficult to fabricate smart vehicles with multiple switching (size, surface, shape) based on biopolymers alone. Here, we report a dual size/charge-switchable and multi-responsive doxorubicin-loaded gelatin-based nanocluster (DOX-icluster) for improved tumor penetration and targeted anti-tumor therapy. The DOX-icluster was electrostatically assembled from folic acid and dimethylmaleic anhydride modified gelatin (FA-GelDMA) and small-sized DOX-loaded NH2 modified hollow mesoporous organosilicon nanoparticles (DOX-HMON-NH2). DOX-icluster had an initial size of about 199 nm at neutral pH. After accumulation in tumor tissue, the DMA bond of FA-GelDMA was cleaved and gelatin was degraded by matrix metalloproteinase (MMP-2), thus 48 nm and positively charged DOX-HMON-NH2 was released to facilitate penetration and cell internalization. DOX-HMON-NH2 was further degraded by intracellular glutathione (GSH) with releasing 48.1 % of DOX. The cellular uptake results indicated that the fabricated icluster promoted the uptake of DOX by 4T1 cells. With enhanced penetration efficacy, the tumor spheroids volume treated with DOX-icluster was reduced to 15.1 % on day 7. This cytocompatible multi-responsive gelatin-based icluster with size-shrinking and charge-reversible characteristics may be used as a significant drug carrier for tumor therapy.

PH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

BackgroundMitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown.ResultsAcid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells.ConclusionsThese promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment.Graphic Abstarct

Multifunctional peptide-conjugated nanocarriers for pulp regeneration in a full-length human tooth root

Dental pulp is a highly vascularized tissue, situated in an inextensible environment surrounded by rigid dentinal walls. The pulp receives its blood supply solely from the small apical foramen of a tooth root. Due to the unique anatomy that controls nutrition supply, regeneration of pulp tissue in a full-length tooth root has long been a challenge in regenerative endodontics. In this study, we designed and synthesized a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector for fast revascularization and pulp regeneration in a full-length human tooth root. The multifunctional peptide was designed to have distinctive features, including a cell-penetrating peptide to enhance cellular uptake, a nuclear localization signal peptide to assist in the translocation of an angiogenic gene into the nucleus, and a fluorescent tryptophan residue to visualize and quantify the transfection efficiency. Furthermore, a pH-sensitive dimethylmaleic anhydride (DMA) was integrated with the multifunctional peptide to enhance the transfected gene complex to escape from endosomes/lysosomes after internalization. In vitro experiments showed that the multifunctional non-viral gene vector significantly increased internalization and gene transfection efficiency as well as reduced cytotoxicity. After dental pulp stem cells (DPSCs) were transfected with the multifunctional gene vector/pVEGF complexes, the expression of VEGF from the DPSCs was upregulated for more than eight folds, which in turn greatly enhanced endothelial cell migration and vascular-like tube formation. Six weeks after implantation, the VEGF-transfected DPSCs accelerated new blood vessel formation and the regenerated pulp tissue occupied most of the area in the canal of a full-length human tooth root. The multifunctional peptide conjugated non-viral gene delivery is a safe and effective approach for regenerative endodontics. Statement of SignificancePulp regeneration in a full-length tooth root canal has long been a challenge in regenerative endodontics. This is due to the unique root anatomy that allows the blood supply of the tooth root only from a small apical foramen (< 1 mm), leading to a severe barrier for revascularization during pulp regeneration. In this work, we designed a multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector to address this challenge. Our work shows that the peptide-conjugated system was an excellent carrier for fast revascularization and pulp tissue regeneration in a full-length toot root. This study will interest the multidisciplinary readership in gene delivery, biomaterials, and dental/craniofacial tissue engineering community.

Multifunctional Peptide-Conjugated Nanocarriers for Pulp Regeneration in a Full-Length Human Tooth Root

Dental pulp is a highly vascularized tissue, situated in an inextensible environment surrounded by rigid dentinal walls. The pulp receives its blood supply solely from the small apical foramen of a tooth root. Due to the unique anatomy that controls nutrition supply, regeneration of pulp tissue in a full-length tooth root has long been a challenge in regenerative endodontics. In this study, we designed and synthesized a novel multifunctional peptide-conjugated, pH-sensitive, non-viral gene vector for fast revascularization and pulp regeneration in a full-length human tooth root. The multifunctional peptide was designed to have distinctive features, including a cell-penetrating peptide to enhance cellular uptake, a nuclear localization signal peptide to assist in the translocation of an angiogenic gene into the nucleus, and a fluorescent tryptophan residue to visualize and quantify the transfection efficiency. Furthermore, a pH-sensitive dimethylmaleic anhydride (DMA) was integrated with the multifunctional peptide to enhance the transfected gene complex to escape from endosomes/lysosomes after internalization. In vitro experiments showed that the multifunctional non-viral gene vector significantly increased internalization and gene transfection efficiency as well as reduced cytotoxicity. After dental pulp stem cells (DPSCs) were transfected with the multifunctional gene vector/pVEGF complexes, the expression of VEGF from the DPSCs was upregulated for more than eight folds, which in turn greatly enhanced endothelial cell migration and vascular-like tube formation. Six weeks after implantation, the VEGF-transfected DPSCs accelerated new blood vessel formation and the regenerated pulp tissue occupied most of the area in the canal of a full-length human tooth root. The multifunctional peptide conjugated non-viral gene delivery is a safe and effective approach for regenerative endodontics.

Charge and Size Dual Switchable Nanocage for Novel Triple-Interlocked Combination Therapy Pattern.

Combination therapy is a current hot topic in cancer treatment. Multiple synergistic effects elicited by combined drugs are essential in improving antitumor activity. Herein, a pH‐triggered charge and size dual switchable nanocage co‐loaded with abemaciclib and IMD‐0354 (PA/PI‐ND) is reported, exhibiting a novel triple‐interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy. The charge reversal polymer NGR‐poly(ethylene glycol)‐poly(l‐lysine)‐dimethylmaleic anhydride (NGR‐PEG‐PLL‐DMA, ND) in PA/PI‐ND promotes the pH‐triggered charge reversal from negative to positive and size reduction from about 180 to 10 nm in an acidic tumor microenvironment, which greatly enhances cellular uptake and tumor tissue deep penetration. With the PA/PI‐ND triple‐interlocked combination therapy, the chemotherapeutic effect is enhanced by the action of abemaciclib to induce cell cycle arrest in the G1 phase, together with the reduction in cyclin D levels caused by IMD‐0354. The dual anti‐tumor promoting immunotherapy is achieved by abemaciclib selectively inhibiting the proliferation of regulatory T cells (Tregs) and by IMD‐0354 promoting tumor‐associated macrophage (TAM) repolarization from an M2 to M1 phenotype. Furthermore, PA/PI‐ND has improved anti‐tumor efficiency resulting from the third synergistic effect provided by chemoimmunotherapy. Taken together, PA/PI‐ND is a promising strategy to guide the design of future drug delivery carriers and cancer combination therapy.

Small Morph Nanoparticles for Deep Tumor Penetration via Caveolae-Mediated Transcytosis.

The tumor penetration of nanomedicines constitutes a great challenge in the treatment of solid tumors, leading to the highly compromised therapeutic efficacy of nanomedicines. Here, we developed small morph nanoparticles (PDMA) by modifying polyamidoamine (PAMAM) dendrimers with dimethylmaleic anhydride (DMA). PDMA achieved deep tumor penetration via an active, energy-dependent, caveolae-mediated transcytosis, which circumvented the obstacles in the process of deep penetration. PDMA remained negatively charged under normal physiological conditions and underwent rapid charge reversal from negative to positive under acidic conditions in the tumor microenvironment (pH < 6.5), which enhanced their uptake by tumor cells and their deep penetration into tumor tissues in vitro and in vivo. The deep tumor penetration of PDMA was achieved mainly by caveolae-mediated transcytosis, which could be attributed to the small sizes (5-10 nm) and positive charge of the morphed PDMA. In vivo studies demonstrated that PDMA exhibited increased tumor accumulation and doxorubicin-loaded PDMA (PDMA/DOX) showed better antitumor efficacy. Overall, the small morph PDMA for enhanced deep tumor penetration via caveolae-mediated transcytosis could provide new inspiration for the design of anticancer drug delivery systems.

ATP Suppression by pH-Activated Mitochondria-Targeted Delivery of Nitric Oxide Nanoplatform for Drug Resistance Reversal and Metastasis Inhibition.

Mitochondria, which are important mediators for cancer initiation, growth, metastasis, and drug resistance, have been considered as a major target in cancer therapy. Herein, an acid-activated mitochondria-targeted drug nanocarrier is constructed for precise delivery of nitric oxide (NO) as an adenosine triphosphate (ATP) suppressor to amplify the therapeutic efficacy in cancer treatments. By combining α-cyclodextrin (α-CD) and acid-cleavable dimethylmaleic anhydride modified PEG conjugated mitochondria-targeting peptide, the nanocarrier shows prolonged blood circulation time and enhanced cellular uptake together with selectively restoring mitochondria-targeting capability under tumor extracellular pH (6.5). Such specific mitochondria-targeted delivery of NO proves crucial in inducing mitochondria dysfunction through facilitating mitochondrial membrane permeabilization and downregulating ATP level, which can inhibit P-glycoprotein-related bioactivities and formation of tumor-derived microvesicles to combat drug resistance and cancer metastasis. Therefore, this pioneering acid-activated mitochondria-targeted NO nanocarrier is supposed to be a malignant tumor opponent and may provide insights for diverse NO-relevant cancer treatments.

Synergistic Charge Reversal with Hierarchical Architecture for Self-Adaptive Antibacterial Surface of Polymer Substrate

The responsive antibacterial efficacy of hierarchical polymer brushes has been well recognized for the treatment of device-associated infection. However, in the previous work, the nanometer-scale thickness of polymer brushes is prone to damage and the reported silicon substrate is not close to practical application. To address these challenges, a self-adaptive antibacterial polymer surface is facilely proposed and designed. Herein, a two-layered polymer brush is first constructed onto the polymer surface, the inner layer of which is conjugated by dimethylmaleic anhydride (DMMA) to produce charge-reversal function, subsequently loading antimicrobial peptides (AMP), and the outer layer of which is a hydrated brush to provide anti-biomass adhesion function. It's worth noting that the micrometer-scale thickness of the inner layer presents the excellent AMP loading capacity. Compared with the charge-neutralization surface, the charge-reversal surface can more sensitively and controllably release AMP triggered by the acidic environment arising from the metabolism of bacteria and may still be bactericidal after AMP is completely released due to the exposure of the primary amino group, thus the long-term antibacterial of the surface is readily obtained. More importantly, in a mice model the charge-reversal surface demonstrates the highly effective anti-infection and excellent biocompatibility, which implies a promising strategy for the clinical prevention of device-associated infections.

Dual-Stimuli-Responsive Polypeptide Nanoparticles for Photothermal and Photodynamic Therapy.

We report the assembly of dual-responsive polypeptide nanoparticles loaded with indocyanine green (ICG) using a mesoporous silica (MS) templating method for photothermal and photodynamic therapy. Polypeptide nanoparticles composed of thiol-modified polylysine (PLL) are cross-linked with disulfide bonds and modified with poly(ethylene glycol) (PEG) and pH-sheddable dimethylmaleic anhydride (DMMA), which exhibit reduction- and pH-responsiveness. Cross-linking with disulfide bonds does not influence the free amine groups on PLL chains for further cargo conjugation and surface modification. The stripped DMMA at acidic pH reverses the zeta potential of PLL nanoparticles from negative to positive charge and subsequently results in high cell association. The thermo-responsiveness and singlet oxygen generation of the loaded ICG in DMMA-modified PLL nanoparticles are comparable to those of free ICG under laser irradiation, which induces higher cytotoxicity to cancer cells compared to succinic anhydride (SA)-modified PLL nanoparticles that are not pH-responsive. The reported dual-responsive PLL nanoparticles provide a promising platform for improved photothermal and photodynamic therapy.

Integrated prodrug micelles with two-photon bioimaging and pH-triggered drug delivery for cancer theranostics.

Nanodrug carriers with fluorescence radiation are widely used in cancer diagnosis and therapy due to their real-time imaging, less side effect, better drug utilization as well as the good bioimaging ability. However, traditional nanocarriers still suffer from unexpectable drug leakage, unsatisfactory tumor-targeted drug delivery and shallow imaging depth, which limit their further application in cancer theranostics. In this study, an integrated nanoplatform is constructed by polymeric prodrug micelles with two-photon and aggregation-induced emission bioimaging, charge reversal and drug delivery triggered by acidic pH. The prodrug micelles can be self-assembled by the TP-PEI (DA/DOX)-PEG prodrug polymer, which consists of the two-photon fluorophore (TP), dimethylmaleic anhydride (DA) grafted polyethyleneimine (PEI) and polyethylene glycol (PEG). The PEG segment, DOX and DA are bridged to polymer by acid cleavable bonds, which provides the micelles a ‘stealth’ property and a satisfactory stability during blood circulation, while the outside PEG segment is abandoned along with the DA protection in the tumor acidic microenvironment, thus leading to charge reversal-mediated accelerated endocytosis and tumor-targeted drug delivery. The great antitumor efficacy and reduced side effect of these pH-sensitive prodrug micelles are confirmed by antitumor assays in vitro and in vivo. Meanwhile, these micelles exhibited great deep-tissue two-photon bioimaging ability up to 150 μm in depth. The great antitumor efficacy, reduced side effect and deep two-photon tissue imaging make the TP-PEI (DA/DOX)-PEG prodrug micelles would be an efficient strategy for theranostic nanoplatform in cancer treatment.

Stepwise pH/reduction-responsive polymeric conjugates for enhanced drug delivery to tumor

In this research, a charge-conversional polymer, poly-l-lysine-lipoic acid (PLL-LA), was prepared by dimethylmaleic anhydride (DA) modification and applied as a carrier with enhanced cell internalization and intracellular pH- and reduction-triggered doxorubicin (Dox) release. The surface charge of dimethylmaleic anhydride-poly-l-lysine-lipoic acid micelles (DA-PLL-LA) was negative at physiological pH and reversed to positive at the extracellular and intracellular pH of cancer cells. At tumor extracellular pH of 6.8, the conjugates underwent a rapid charge-reversible process with almost 80% DA cleavage within 2h, and then endocytosed into the endo/lysosomes more rapidly than at physiological pH of 7.4. The Dox/DA-PLL-LA micelles (Dox-micelles) demonstrated a sustained drug release in vitro under physiological condition, and rapid Dox release was triggered by both extracellular pH and high-concentration reducing glutathione. The Dox-micelles also exhibited enhanced internalization at extracellular pH, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Excellent tumor-penetrating efficacy was also found in A549 tumor spheroids and solid tumor slices. Moreover, the DA-PLL-LA micelles exhibited excellent tumor-targeting ability in tumor tissues and excellent antitumor efficacy and low systemic toxicity in breast tumor-bearing mice. Therefore, the DA-PLL-LA micelles demonstrated great potential for targeted and efficient drug delivery in cancer treatments.

Preparations of hyperbranched polymer nano micelles and the pH/redox controlled drug release behaviors

Hyperbranched polymer nano micelles (NMs) were prepared through a nucleophilic ring opening polymerization between cystamine and polyethylene glycol diglycidyl ether, followed by a reaction of amino groups and dimethyl maleic anhydride. The NMs showed spheric morphologies with hydrodynamic diameters of 106–120nm. Doxorubicin was loaded in the NMs with loading rate as high as 15.38wt%; The NMs possessed negative zeta potentials in aqueous solutions of pH7.4 due to the carboxyl ions on the particle surfaces, but the zeta potentials were converted to positive ones due to the hydrolysis of amide bonds at pH5.0–6.5, leading to the leaving of carboxyl groups and remaining of amino groups. The disulfide bonds in cystamine were designed in the hyperbranched polymer structures of the NMs, and bonds could be broken by a reducing agent l-glutathione (GSH) (10mM), resulting in a targeted drug release. The smart NMs displayed good biodegradability and biocompatibility, and they could be potentially used in drug controlled release field.

Molecular characterization of methanogenic N5-methyl-tetrahydromethanopterin: Coenzyme M methyltransferase

Methanogenic archaea share one ion gradient forming reaction in their energy metabolism catalyzed by the membrane-spanning multisubunit complex N5-methyl-tetrahydromethanopterin: coenzyme M methyltransferase (MtrABCDEFGH or simply Mtr). In this reaction the methyl group transfer from methyl-tetrahydromethanopterin to coenzyme M mediated by cobalamin is coupled with the vectorial translocation of Na+ across the cytoplasmic membrane. No detailed structural and mechanistic data are reported about this process. In the present work we describe a procedure to provide a highly pure and homogenous Mtr complex on the basis of a selective removal of the only soluble subunit MtrH with the membrane perturbing agent dimethyl maleic anhydride and a subsequent two-step chromatographic purification. A molecular mass determination of the Mtr complex by laser induced liquid bead ion desorption mass spectrometry (LILBID-MS) and size exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) resulted in a (MtrABCDEFG)3 heterotrimeric complex of ca. 430kDa with both techniques. Taking into account that the membrane protein complex contains various firmly bound small molecules, predominantly detergent molecules, the stoichiometry of the subunits is most likely 1:1. A schematic model for the subunit arrangement within the MtrABCDEFG protomer was deduced from the mass of Mtr subcomplexes obtained by harsh IR-laser LILBID-MS.

Enhanced Therapeutic siRNA to Tumor Cells by a pH-Sensitive Agmatine-Chitosan Bioconjugate.

Charge-conversional naturally occurring chitosan-agmatine bioconjugates are prepared by dimethylmaleic anhydride (DMA) modification and the nucleophilic reaction between tosyl of tosylated chitosan and primary amine of agmatine. These bioconjugates (CS-DM-Agm) are shown to condense siRNA into nanocomplexes, which are stable in the presence of serum at physical pH values. Furthermore, the surface charge of complexes can tune from negative to positive while pH is changed to weak acid tumor micromilieu, thus facilitating the target cancer cell internalization in resisting serum adsorption. More importantly, this smart biogenic system shows remarkable gene silencing efficiency and a high apoptotic rate of tumor cells both in vitro and in vivo, indicating its great potential for cancer therapy.

ChemInform Abstract: A Concise Account of the Chemistry of Valuable Alkyl(methyl)maleic Anhydrides

AbstractReview: [90 refs.

A Concise Account of the Chemistry of Valuable Alkyl(methyl)maleic Anhydrides

A large number of significant bioactive natural and synthetic alkyl(methyl)maleic anhydrides are known in the contemporary literature. A broad range of suitably functionalized substrates have been tailored to accomplish concise and efficient syntheses of an array of alkyl(methyl)maleic anhydrides employing a variety of elegant synthetic strategies. This review presents a brief literature account of the isolation and activity of these important target compounds with a special emphasis on their synthesis. 1 Introduction 2 Recent Synthetic Strategies towards the Natural and Unnatural Alkyl(methyl)maleic Anhydrides 2.1 Dimethylmaleic Anhydride 2.2 Ethyl/hexyl/octyl(methyl)maleic Anhydrides 2.3 Chaetomellic Anhydrides A–C 2.4 Tyromycin A 2.5 Aspergillus Acids A–D 2.6 Tautomycin and Tautomycetin 2.7 Lindenanolide E, Itaconitin, Graphenone and 2,3-Didehydrotelfairic Anhydride 2.8 Synthetic Analogues of Alkyl(methyl)maleic Anhydrides 3 Summary

New Hydrogels Based on Substituted Anhydride Modified Collagen and 2-Hydroxyethyl Methacrylate. Synthesis and Characterization

Semi-interpenetrated networks were obtained by free radical polymerization/cross-linking of substituted anhydride modified collagen with 2-hydroxyethyl methacrylate (HEMA) in the presence of ammonium persulfate (APS) and N,N,N′,N′-tetramethyl ethylene diamine (TEMED). Substituted anhydride modified collagens, porous materials with vinyl groups, have been previously synthesized by reaction of soluble collagen with dimethyl maleic anhydride (DMA) or citraconic anhydride (CTA). The structure and physicochemical properties of the obtained hydrogels were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), and water retention studies. Thermal properties of substituted anhydride modified collagen and their corresponding hydrogels have been investigated by differential scanning calorimetry (DSC) in dried and hydrated states. The denaturation temperature (Td), denaturation enthalpy, and glass transition temperature (Tg) have been determined, and they were found to be depend...