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1.
J Biomol Struct Dyn ; : 1-15, 2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37551015

ABSTRACT

During last decades, 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thione scaffold remains the center of interest due to their ease of preparation, diverse range substituents at N-3 and N-5 positions, and profound biological activities. In the current study, a series of 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thiones were synthesized in good to excellent yield, and the structure of the compounds were confirmed by various spectroscopic techniques such as FTIR, 1H-NMR, 13C-NMR and Mass spectrometry, and finally evaluated against Leishmania major. Whereas, all the evaluated compounds (1-33), demonstrate potential leishmanicidal activities with IC50 values in the range of (1.30- 149.98 uM). Among the evaluated compounds such as 3, 4, 6, and 10 exhibited excellent leishmanicidal activities with IC50 values of (2.17 µM), (2.39 µM), (2.00 µM), and (1.39 µM), respectively even better than the standard amphotericin B (IC50 = 0.50) and pentamidine (IC50 = 7.52). In order to investigate binding interaction of the most active compounds, molecular docking study was conducted with Leishmania major. Further molecular dynamic simulation study was also carried out to assess the stability and correct binding of the most active compound 10, within active site of the Leishamania major. Likewise, the physiochemical properties, drug likeness, and ADMET of the most active compounds were investigated, it was found that none of the compounds violate Lipiniski's rule of five, which show that this class of compounds had enough potential to be used as drug candidate in near future.Communicated by Ramaswamy H. Sarma.

2.
ACS Omega ; 8(23): 20412-20422, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37332823

ABSTRACT

Dihydropyrazole (1-22) derivatives were synthesized from already synthesized chalcones. The structures of all of the synthesized compounds were confirmed by elemental analysis and various spectroscopic techniques. Furthermore, the synthesized compounds were screened against α amylase as well as investigated for antioxidant activities. The synthesized compounds demonstrate good to excellent antioxidant activities with IC50 values ranging between 30.03 and 913.58 µM. Among the 22 evaluated compounds, 11 compounds exhibit excellent activity relative to the standard ascorbic acid IC50 = 287.30 µM. Interestingly, all of the evaluated compounds show good to excellent α amylase activity with IC50 values lying in the range between 0.5509 and 810.73 µM as compared to the standard acarbose IC50 = 73.12 µM. Among the investigated compounds, five compounds demonstrate better activity compared to the standard. In order to investigate the binding interactions of the evaluated compounds with amylase protein, molecular docking studies were conducted, which show an excellent docking score as compared to the standard. Furthermore, the physiochemical properties, drug likeness, and ADMET were investigated, and it was found that none of the compounds violate Lipiniski's rule of five, which shows that this class of compounds has enough potential to be used as a drug candidate in the near future.

3.
Polymers (Basel) ; 15(10)2023 May 16.
Article in English | MEDLINE | ID: mdl-37242892

ABSTRACT

Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.

4.
J Biomater Sci Polym Ed ; 34(12): 1683-1701, 2023 08.
Article in English | MEDLINE | ID: mdl-37058125

ABSTRACT

Sodium alginate is a polyanionic natural polysaccharide polymer widely used in tissue engineering. However, the lack of binding domains for interaction with cells limits its application in regenerative medicine. This study designed a kind of galactosylated sodium alginate (G-SA) material with improved galactose grafting rate by EDC/NHS activation of carboxyl groups in MES buffer and subsequently cross-linking by Ca2+ aims to enhance the adherence behavior of HepG2 cells on alginate substrate. The synthesized G-SA was characterized by Fourier transform infrared spectra and nuclear magnetic resonance spectroscopy. G-SA exhibited good biocompatibility and significantly enhanced the adhesion behavior of HepG2 cells on its surface. Furthermore, we demonstrated that the effect of G-SA concentration in enhancing cell adhesion was diminished at higher than 2% w/v. Finally, the suitability of G-SA material is investigated for 3D printing, demonstrating that HepG2 cells could maintain high viability and excellent printability in the interior of the gel. In addition, cells could multiply and grow into cell spheroids with an average size of 200 µm in G-SA scaffolds. These results indicated that galactosylated sodium alginate material could be used as a 3D culture system that could be effective for engineering liver cancer models.


Subject(s)
Alginates , Tissue Scaffolds , Humans , Tissue Scaffolds/chemistry , Alginates/chemistry , Hep G2 Cells , Tissue Engineering/methods , Polymers , Printing, Three-Dimensional
5.
Biomater Sci ; 11(11): 3840-3850, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37074080

ABSTRACT

Low immune infiltration severely hinders the efficacy of cancer immunotherapy. Here, we developed a manganese-phenolic network platform (TMPD) to boost antitumor immunity via a stimulator of interferon gene (STING)-amplified activation cascade. TMPD is based on doxorubicin (DOX)-loaded PEG-PLGA nanoparticles and further coated with manganese (Mn2+)-tannic acid (TA) networks. Mechanistically, DOX-based chemotherapy and Mn2+-mediated chemodynamic therapy effectively promoted immunogenic cell death (ICD), characterized by abundant damage-associated molecular pattern (DAMP) exposure, which subsequently enhanced dendritic cells' (DCs) presentation of antigens. DOX-elicited DNA damage simultaneously caused cytoplasmic leakage of intracellular double-stranded DNA (dsDNA) as the STING signal initiator, while Mn2+ mediated significant upregulation in the expression of a STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of TMPD remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Meanwhile, the released Mn2+ could serve as a contrast agent for tumor-specific T1-weighted magnetic resonance imaging (MRI). Moreover, TMPD combined with immune checkpoint blockade (ICB) immunotherapy significantly inhibited tumor growth and lung metastasis. Collectively, these findings indicate that TMPD has great potential in activating robust innate and adaptive immunity for MRI guided cancer chemo-/chemodynamic/immune therapy.


Subject(s)
Manganese , Neoplasms , Humans , Magnetic Resonance Imaging , Immunotherapy , Up-Regulation , Cell Line, Tumor , Tumor Microenvironment
6.
Molecules ; 27(11)2022 May 26.
Article in English | MEDLINE | ID: mdl-35684380

ABSTRACT

Three-dimensional (3D) bioprinting is one of the most promising additive manufacturing technologies for fabricating various biomimetic architectures of tissues and organs. In this context, the bioink, a critical element for biofabrication, is a mixture of biomaterials and living cells used in 3D printing to create cell-laden structures. Recently, decellularized extracellular matrix (dECM)-based bioinks derived from natural tissues have garnered enormous attention from researchers due to their unique and complex biochemical properties. This review initially presents the details of the natural ECM and its role in cell growth and metabolism. Further, we briefly emphasize the commonly used decellularization treatment procedures and subsequent evaluations for the quality control of the dECM. In addition, we summarize some of the common bioink preparation strategies, the 3D bioprinting approaches, and the applicability of 3D-printed dECM bioinks to tissue engineering. Finally, we present some of the challenges in this field and the prospects for future development.


Subject(s)
Bioprinting , Bioprinting/methods , Decellularized Extracellular Matrix , Extracellular Matrix/metabolism , Printing, Three-Dimensional , Tissue Engineering/methods , Tissue Scaffolds/chemistry
7.
Sci Technol Adv Mater ; 22(1): 695-717, 2021.
Article in English | MEDLINE | ID: mdl-34512177

ABSTRACT

In recent times, the supercritical carbon dioxide (scCO2) process has attracted increasing attention in fabricating diverse materials due to the attractive features of environmentally benign nature and economically promising character. Owing to these unique characteristics and high-penetrability, as well as diffusivity conditions of scCO2, this high-pressure technology, with mild operation conditions, cost-effective, and non-toxic, among others, is often applied to fabricate various organic and inorganic-based materials, resulting in the unique crystal architectures (amorphous, crystalline, and heterojunction), tunable architectures (nanoparticles, nanosheets, and aerogels) for diverse applications. In this review, we give an emphasis on the fabrication of various inorganic-based materials, highlighting the recent research on the driving factors for improving the quality of fabrication in scCO2, procedures for production and dispersion in scCO2, as well as common indicators utilized to assess quality and processing ability of materials. Next, we highlight the effects of specific properties of scCO2 towards synthesizing the highly functional inorganic-based nanomaterials. Finally, we summarize this compilation with interesting perspectives, aiming to arouse a more comprehensive utilization of scCO2 to broaden the horizon in exploring the green/eco-friendly processing of such versatile inorganic-based materials. Together, we firmly believe that this compilation endeavors to disclose the latent capability and universal prevalence of scCO2 in the synthesis and processing of inorganic-based materials.

8.
Nanomaterials (Basel) ; 10(2)2020 Feb 13.
Article in English | MEDLINE | ID: mdl-32070047

ABSTRACT

Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 23 factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics.

9.
ACS Appl Mater Interfaces ; 11(32): 28781-28790, 2019 Aug 14.
Article in English | MEDLINE | ID: mdl-31252501

ABSTRACT

Despite their inherent efficacy in significantly accelerating the rate of chemical reactions in biological processes, the applicability of natural enzymes is often hindered because of their intrinsic limitations such as high sensitivity, poor operational stability, and relatively high cost for purification as well as preparation. Thus, the fabrication of catalytically active nanomaterials as artificial enzymes (nanozymes) has become a newly burgeoning area of research in bionic chemistry, aiming in designing functional nanomaterials that mimic various inherent properties of natural enzymes. To address these issues, we present the supercritical fluid (SCF)-assisted fabrication of discrete, monodisperse, and uniform-sized manganese (III) oxide (Mn2O3)-based hollow containers as high-efficiency nanozymes for glucose sensing characteristics. Initially, the core-shell nanoreactors based on polyvinylpyrrolidone (PVP)-encapsulated manganese (III) acetylacetonate (Mn(acac)3) as precursors are fabricated using the SCF technology and subsequent calcination resulted in the Mn2O3 hollow nanoparticles (MHNs). This eco-friendly approach has resulted in the PVP-coated Mn(acac)3 nanoreactors with an average diameter of 220 nm and subsequent calcined hollow products are about one-fifth to that of the precursor. Such MHNs conveniently catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) as a prominent peroxidase mimic, resulting in the oxidation products (TMB*+) at a specific absorption (UV-vis) maxima of 652 nm. Following typical Michaelis-Menten theory, this approach is further utilized to develop visual nonenzymatic sensing of glucose in a linear range of 0.1-1 mM at a detection limit of 2.31 µM. Collectively, this reliable as well as a cost-effective system with high precision potentially allows rapid detection of analytes, providing a convenient way for its utilization in diverse fields.


Subject(s)
Glucose/analysis , Manganese/chemistry , Nanoparticles/chemistry , Peroxidase/chemistry , Benzidines/chemistry , Catalysis , Hydrogen Peroxide/chemistry , Limit of Detection
10.
Adv Healthc Mater ; 8(10): e1900047, 2019 05.
Article in English | MEDLINE | ID: mdl-30920772

ABSTRACT

Manganese dioxide (MnO2 )-based nanoparticles are a promising tumor microenvironment-responsive nanotheranostic carrier for targeted magnetic resonance imaging (MRI) and for alleviating tumor hypoxia. However, the complexity and potential toxicity of the present common synthesis methods limit their clinical application. Herein, multifunctional hyaluronic acid-MnO2 nanoparticles (HA-MnO2 NPs) are synthesized in a simple way by directly mixing sodium permanganate with HA aqueous solutions, which serve as both a reducing agent and a surface-coating material. The obtained HA-MnO2 NPs show an improved water-dispersibility, fine colloidal stability, low toxicity, and responsiveness to the tumor microenvironment (high H2 O2 and high glutathione, low pH). After intravenous injection, HA-MnO2 NPs exhibit a high imaging sensitivity for detecting rat intracranial glioma with MRI for a prolonged period of up to 3 d. These nanoparticles also effectively alleviate the tumor hypoxia in a rat model of intracranial glioma. The downregulation of VEGF and HIF-1α expression in intracranial glioma validates the sustained attenuation effect of HA-MnO2 NPs on tumor hypoxia. These results show that HA-MnO2 NPs can be used for sensitive, targeted MRI detection of gliomas and simultaneous attenuation of tumor hypoxia.


Subject(s)
Glioma/diagnostic imaging , Hyaluronic Acid/chemistry , Magnetic Resonance Imaging , Manganese Compounds/chemistry , Nanoparticles/chemistry , Oxides/chemistry , Tumor Hypoxia , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Contrast Media/chemistry , Disease Models, Animal , Glioma/pathology , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Male , Nanoparticles/metabolism , Nanoparticles/toxicity , Rats , Rats, Wistar , Tissue Distribution , Tumor Microenvironment , Vascular Endothelial Growth Factor A/metabolism
11.
Int J Nanomedicine ; 12: 3365-3374, 2017.
Article in English | MEDLINE | ID: mdl-28490876

ABSTRACT

The intraoperative precision cleaning of lymph nodes (LNs) is an essential component of treating neoplastic disease. To develop efficient probes for the targeted detection of LNs that could act as carriers for the specific diagnosis and treatment of metastatic LNs in the future, dextran-coated iron oxide nanoclusters (DIONs) were synthesized using a one-pot coprecipitation procedure. These modified DIONs have good water dispersibility, cytocompatibility, an optimum size, and a stable, dark brown color for LN imaging. In this study, cytotoxicity was evaluated using lymphatic endothelial cells (LECs) to predict biosafety and biocompatibility. Most importantly, the effectiveness of DIONs in mapping perigastric LNs in Sprague Dawley rats following injection into the gastric submucosal layer was demonstrated. In addition, a long-term tracing in vivo (from 4 days to 3 months) indicated that the DIONs had good biosafety and biocompatibility according to an evaluation of the behavior and blood biochemistry of the rat and a histopathological examination of the important organs.


Subject(s)
Dextrans/chemistry , Ferric Compounds/chemistry , Lymphatic Metastasis/diagnostic imaging , Nanostructures/chemistry , Animals , Endothelial Cells/drug effects , Female , Gastric Mucosa/drug effects , Injections , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Nanostructures/administration & dosage , Rats , Rats, Sprague-Dawley , Spectrometry, Fluorescence/methods , Tissue Distribution
12.
J Biomater Appl ; 31(8): 1169-1181, 2017 03.
Article in English | MEDLINE | ID: mdl-28185478

ABSTRACT

The gene and drug co-delivery system has become one of the primary strategies to overcome cancers. Here, we designed a multifunctional magnetic co-delivery system for nasopharyngeal carcinoma-targeted therapy and MR imaging. Aldehyde sodium alginate (ASA) was used to decorate the oxide iron and load cisplain through coordinate bond to form a core complex. The polymer shell poly(l-lysine)-methoxy-polyethylene glycol-folate was used to coat the core complex through electric interaction to give this nano-medicine a target ability. And this polymer could also give the nano-medicine abilities to adhere and protect DNA, and enhance its solubleness in water. After being transfected with this nano-medicine, the plasmids which contain cancer suppressor gene TFPI2 could enter and express in HNE-1 cells. It caused a higher death and apoptosis rate, inhibited nasopharyngeal carcinoma cells' migration and cloning by the synergic effect together with cisplain. Besides, clear images of this nano-medicine could be got under T2 MR imaging. This magnetic co-delivery system demonstrates a potential as a powerful multifunctional vector for drug delivery and gene vector applications in nasopharyngeal carcinoma.


Subject(s)
Carcinoma/diagnostic imaging , Carcinoma/therapy , Folic Acid/pharmacokinetics , Genetic Therapy/methods , Magnetic Resonance Imaging/methods , Magnetite Nanoparticles/chemistry , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/therapy , Polyethylene Glycols/chemistry , Polylysine/analogs & derivatives , Carcinoma/metabolism , Cell Line, Tumor , Coated Materials, Biocompatible/chemical synthesis , Contrast Media/administration & dosage , Folic Acid/chemistry , Humans , Molecular Targeted Therapy/methods , Nanocapsules/administration & dosage , Nanocapsules/chemistry , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/metabolism , Plasmids/administration & dosage , Plasmids/chemistry , Polylysine/chemistry , Theranostic Nanomedicine/methods , Treatment Outcome
13.
Int J Nanomedicine ; 12: 197-206, 2017.
Article in English | MEDLINE | ID: mdl-28096667

ABSTRACT

Theranostic nanoparticles with both imaging and therapeutic abilities are highly promising in successful diagnosis and treatment of the most devastating cancers. In this study, the dual-modal imaging and photothermal effect of hyaluronan (HA)-modified superparamagnetic iron oxide nanoparticles (HA-SPIONs), which was developed in a previous study, were investigated for CD44 HA receptor-overexpressing breast cancer in both in vitro and in vivo experiments. Heat is found to be rapidly generated by near-infrared laser range irradiation of HA-SPIONs. When incubated with CD44 HA receptor-overexpressing MDA-MB-231 cells in vitro, HA-SPIONs exhibited significant specific cellular uptake and specific accumulation confirmed by Prussian blue staining. The in vitro and in vivo results of magnetic resonance imaging and photothermal ablation demonstrated that HA-SPIONs exhibited significant negative contrast enhancement on T2-weighted magnetic resonance imaging and photothermal effect targeted CD44 HA receptor-overexpressing breast cancer. All these results indicated that HA-SPIONs have great potential for effective diagnosis and treatment of cancer.


Subject(s)
Breast Neoplasms/diagnostic imaging , Dextrans/chemistry , Hyaluronic Acid/chemistry , Magnetic Resonance Imaging/methods , Magnetite Nanoparticles/therapeutic use , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Cell Line, Tumor , Contrast Media/chemistry , Dextrans/pharmacokinetics , Female , Humans , Hyaluronan Receptors/metabolism , Magnetite Nanoparticles/chemistry , Mice, Inbred BALB C , Theranostic Nanomedicine/methods , Xenograft Model Antitumor Assays
14.
Mater Sci Eng C Mater Biol Appl ; 67: 159-169, 2016 Oct 01.
Article in English | MEDLINE | ID: mdl-27287110

ABSTRACT

Gliomas are the most common and lethal type of primary malignant brain tumor. But the existence of blood brain barrier (BBB) and blood-tumor barrier (BTB) hinder drug from reaching the tumor site. To address this problem, we developed a novel prodrug (Lf-HA-DOX) by conjugating hyaluronic acid with doxorubicin (HA-DOX) by an acid-labile hydrazone linkage, which is released in an acidic environment and accumulates in tumor tissues. Lactoferrin (Lf) was coupled for transporting across the BBB. In vitro, the release of DOX from Lf-HA-DOX was pH-dependent. At lower pH (5.0 and 6.0), the release of DOX was much quicker than that at pH7.4. In the cellular uptake studies, flow cytometry analyses and confocal laser scanning microscopy results showed significantly enhanced cellular uptake of Lf-HA-DOX and HA-DOX in C6 cells compared to DOX. In BALB/C mice bearing C6 glioma, enhanced accumulation of Lf-HA-DOX in the glioma was observed by real time fluorescence image. Correspondingly, glioma-bearing mice treated with Lf-HA-DOX displayed the longest median survival time, which was 2-fold longer than that of saline group. In conclusion, Lf-HA-DOX was able to significantly increase drug delivery to the glioma, which might provide a promising strategy for antiglioma therapy.


Subject(s)
Doxorubicin , Glioma/drug therapy , Hyaluronic Acid , Lactoferrin , Prodrugs , Animals , Cell Line, Tumor , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Glioma/metabolism , Glioma/pathology , Humans , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacokinetics , Hyaluronic Acid/pharmacology , Hydrogen-Ion Concentration , Lactoferrin/chemistry , Lactoferrin/pharmacokinetics , Lactoferrin/pharmacology , Mice , Mice, Nude , Prodrugs/chemistry , Prodrugs/pharmacokinetics , Prodrugs/pharmacology , Rats , Xenograft Model Antitumor Assays
15.
Carbohydr Polym ; 128: 163-70, 2015 Sep 05.
Article in English | MEDLINE | ID: mdl-26005152

ABSTRACT

A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by (1)H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Hyaluronic Acid/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Drug Liberation , Humans , Hydrazones/chemistry , Hydrogels , Hydrogen-Ion Concentration , Sulfhydryl Compounds/chemistry
16.
Mater Sci Eng C Mater Biol Appl ; 45: 556-63, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25491864

ABSTRACT

To develop an efficient probe for targeted magnetic resonance (MR) imaging of liver carcinoma, the surface modification of superparamagnetic iron oxide nanoparticles (SPIONs) was carried out by conjugating a naturally-occurring glycosaminoglycan with specific biological recognition to human hepatocellular liver carcinoma (HepG2) cells. These modified SPIOs have good water dispersibility, superparamagnetic property, cytocompatibility and high magnetic relaxivity for MR imaging. When incubated with HepG2 cells, they demonstrated significant cellular uptake and specific accumulation, as confirmed by Prussian blue staining and confocal microscopy. The in vitro MR imaging of HepG2 cells and in vivo MR imaging of HepG2 tumors confirmed their effectiveness for targeted MR imaging of liver carcinoma.


Subject(s)
Contrast Media/chemistry , Ferric Compounds/chemistry , Glycosaminoglycans/chemistry , Magnetite Nanoparticles/chemistry , Amines/chemistry , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Cell Survival/drug effects , Contrast Media/metabolism , Hep G2 Cells , Humans , Hyaluronan Receptors/chemistry , Hyaluronan Receptors/metabolism , Hyaluronic Acid/chemistry , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Magnetite Nanoparticles/toxicity , Microscopy, Confocal , Particle Size , Radiography , Spectroscopy, Fourier Transform Infrared
17.
Mater Sci Eng C Mater Biol Appl ; 36: 287-93, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-24433914

ABSTRACT

To develop biocompatible polymeric hydrogels for the in-situ encapsulation and controlled release of hydrophilic drugs, the oxidized hyaluronic acid containing aldehyde groups was prepared by the reaction between hyaluronic acid and sodium periodate, and then used for the first time to crosslink casein protein in aqueous system. By changing its aldehyde group content or amount, we found that the gelation kinetics and the properties of resultant composite hydrogel could be modulated. Particularly, an increase of its aldehyde group content or amount was found to result in a shorten gelation time, an enhanced gel strength, a reduced swelling ratio and a prolonged drug release. In addition, the as obtained composite hydrogel was also evaluated for its in vitro cytotoxicity on L929 mouse fibroblast cells and was confirmed to have a good biocompatibility.


Subject(s)
Biocompatible Materials/chemistry , Caseins/chemistry , Delayed-Action Preparations/pharmacology , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Animals , Cell Death/drug effects , Cell Survival/drug effects , Cells, Cultured , Elastic Modulus/drug effects , Fibroblasts/cytology , Fibroblasts/drug effects , Kinetics , Mice , Microscopy, Electron, Scanning , Oxidation-Reduction , Salicylic Acid/pharmacology , Viscosity/drug effects
18.
Nan Fang Yi Ke Da Xue Xue Bao ; 27(5): 602-4, 2007 May.
Article in Chinese | MEDLINE | ID: mdl-17545066

ABSTRACT

OBJECTIVE: To investigate the protective effect of hepatocyte growth factor (HGF) on protein synthesis in rat cardiomyocytes exposed to gamma-ray irradiation. METHODS: Primary cultured cardiomyocytes were irradiated with single-dose (20 Gy) gamma ray in the absence or presence of HGF (40 ng/ml) added in the cell culture 3 h before the exposure. Forty-eight hours after irradiation, the total cellular protein was measured and cell cycle analyzed by flow cytometry. The cardiomyoctes were also infected with AdGFP 48 h after irradiation and the fluorescence intensity of the green fluorescence protein (GFP) in the cells determined by flow cytometry 48 h after infection. RESULTS: The protein synthesis was decreased significantly in the irradiated cardiomyocytes as compared with the control group (P<0.01), but was remedied significantly by incubation of the cells with HGF before the exposure (P<0.05). Flow cytometry revealed much lower mean fluorescence intensity (MFI) of GFP in irradiated cardiomycytes than in cells without the exposure (P<0.01); The MFI was higher in HGF-treated cardiomyocytes than in cells without HGF treatment following the exposure (P<0.01). CONCLUSION: Gamma ray irradiation inhibits protein synthesis in cardiomyocytes, and HGF may attenuate this effect of gamma ray exposure for cardiomyocyte protection.


Subject(s)
Hepatocyte Growth Factor/pharmacology , Myocytes, Cardiac/metabolism , Protein Biosynthesis/drug effects , Protein Biosynthesis/radiation effects , Animals , Animals, Newborn , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cells, Cultured , Flow Cytometry , Gamma Rays , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Microscopy, Fluorescence , Myocytes, Cardiac/cytology , Rats , Rats, Wistar
19.
Article in English | MEDLINE | ID: mdl-12219211

ABSTRACT

A method of the simultaneous purification of cardiac troponin T (cTnT) and troponin I (cTnI) from human cardiac left ventricular muscle have been developed. Five mg cTnT and 10.2 mg of cTnI were obtained from 100 mg of cardiac muscle. The purity of cTnT and cTnI could reach to 97.6% and 97.2% respectively. Their immunoactivity and specificity have been identified by ELISA method.

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