首页 | 官方网站   微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
Geldanamycin (GM) is an inhibitor of heat shock protein 90 (Hsp90) with potent and broad anti-cancer properties, but with unacceptable levels of hepatotoxicity. These characteristics have led to the devise of a range of less toxic GM structural analogues. Redox properties and thiol reactivity are central to the therapeutic and toxicologic effects of quinones, and the question arises as to whether the toxicity of GM and its analogues relates to the reduction potential of the quinone. Using pulse radiolysis, we have previously determined the one-electron reduction potentials (vs. the normal hydrogen electrode [NHE]) at pH 7.0 of GM, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), and 17-allylamino-17-demethoxygeldanamycin (17-AAG) to be −62±7 mV, −194±6 mV, and −273±8 mV, respectively. These experimental results are now used to establish a predictive relationship for the reduction potential of GM analogues based on the Hammett para substituent constants. These values correlate well with the drugs effects in vivo. We show that cytotoxicity of the benzoquinone ansamycin increases as its respective reduction potential increases, even after blocking of the C19-position from nucleophilic addition. We conclude that the cytotoxicity is directly related to the reduction potential of the quinone/semiquinone couple.  相似文献   

2.
Gelatin (Gel)-based pH- and thermal-responsive magnetic hydrogels (MH-1 and MH-2) were designed and developed as novel drug delivery systems (DDSs) for cancer chemo/hyperthermia therapy. For this goal, Gel was functionalized with methacrylic anhydride (GelMA), and then copolymerized with (2-dimethylaminoethyl) methacrylate (DMAEMA) monomer in the presence of methacrylate-end capped magnetic nanoparticles (MNPs) as well as triethylene glycol dimethacrylate (TEGDMA; as crosslinker). Afterward, a thiol-end capped poly(N-isopropylacrylamide) (PNIPAAm-SH) was synthesized through an atom transfer radical polymerization technique, and then attached onto the hydrogel through “thiol-ene” click grafting. The preliminary performances of developed MHs for chemo/hyperthermia therapy of human breast cancer was investigated through the loading of doxorubicin hydrochloride (Dox) as an anticancer agent followed by cytotoxicity measurement of drug-loaded DDSs using MTT assay by both chemo- and chemo/hyperthermia-therapies. Owing to porous morphologies of the fabricated magnetic hydrogels according to scanning electron microscopy images and strong physicochemical interactions (e.g., hydrogen bonding) the drug loading capacities of the MH-1 and MH-2 were obtained as 72 ± 1.4 and 77 ± 1.8, respectively. The DDSs exhibited acceptable pH- and thermal-triggered drug release behaviors. The MTT assay results revealed that the combination of hyperthermia therapy and chemotherapy has synergic effect on the anticancer activities of the developed DDSs.  相似文献   

3.
Nanofibers are one-dimensional nanomaterial in fiber form with diameter less than 1 µm and an aspect ratio (length/diameter) larger than 100:1. Among the different types of nanoparticle-loaded nanofiber systems, nanofibers loaded with magnetic nanoparticles have gained much attention from biomedical scientists due to a synergistic effect obtained from the unique properties of both the nanofibers and magnetic nanoparticles. These magnetic nanoparticle-encapsulated or -embedded nanofiber systems can be used not only for imaging purposes but also for therapy. In this review, we focused on recent advances in nanofibers loaded with magnetic nanoparticles, their biomedical applications, and future trends in the application of these nanofibers.  相似文献   

4.
Different chemical agents are used for the biocompatibility and/or functionality of the nanoparticles used in magnetic hyperthermia to reduce or even eliminate cellular toxicity and to limit the interaction between them (van der Waals and magnetic dipolar interactions), with highly beneficial effects on the efficiency of magnetic hyperthermia in cancer therapy. In this paper we propose an innovative strategy for the biocompatibility of these nanoparticles using gamma-cyclodextrins (γ-CDs) to decorate the surface of magnetite (Fe3O4) nanoparticles. The influence of the biocompatible organic layer of cyclodextrins, from the surface of Fe3O4 ferrimagnetic nanoparticles, on the maximum specific loss power in superparamagnetic hyperthermia, is presented and analyzed in detail in this paper. Furthermore, our study shows the optimum conditions in which the magnetic nanoparticles covered with gamma-cyclodextrin (Fe3O4–γ-CDs) can be utilized in superparamagnetic hyperthermia for an alternative cancer therapy with higher efficiency in destroying tumoral cells and eliminating cellular toxicity.  相似文献   

5.
Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH‐sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Because of the released drug, the particles were found to be cytotoxic to human breast cancer cells in vitro. Such magnetic nanoparticles, with the potential to retain drug under physiological conditions and release the drug in conditions where the pH is lower or temperature is higher, may be useful in magnetic drug targeting by reducing the side effects of the drug caused to healthy tissues. In addition, they may serve as hyperthermia agents where the high temperatures used in hyperthermia can trigger further drug release. © 2010 American Institute of Chemical Engineers AIChE J, 2011  相似文献   

6.
Abstract  As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT) is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs) were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl) porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4) and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy. Graphical Abstract   Novel multifunctional photosensitizer loaded magnetic silica nanoparticles were strategically prepared with low toxicity, good biocompatibility and remarkable photodynamic anti-tumor efficacy. The nanoparticles were believed to be of great value as drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.   相似文献   

7.
In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.  相似文献   

8.
The ClC-2 channel plays a critical role in maintaining ion homeostasis in the brain and the testis. Loss-of-function mutations in the ClC-2-encoding human CLCN2 gene are linked to the white matter disease leukodystrophy. Clcn2-deficient mice display neuronal myelin vacuolation and testicular degeneration. Leukodystrophy-causing ClC-2 mutant channels are associated with anomalous proteostasis manifesting enhanced endoplasmic reticulum (ER)-associated degradation. The molecular nature of the ER quality control system for ClC-2 protein remains elusive. In mouse testicular tissues and Leydig cells, we demonstrated that endogenous ClC-2 co-existed in the same protein complex with the molecular chaperones heat shock protein 90β (Hsp90β) and heat shock cognate protein (Hsc70), as well as the associated co-chaperones Hsp70/Hsp90 organizing protein (HOP), activator of Hsp90 ATPase homolog 1 (Aha1), and FK506-binding protein 8 (FKBP8). Further biochemical analyses revealed that the Hsp90β-Hsc70 chaperone/co-chaperone system promoted mouse and human ClC-2 protein biogenesis. FKBP8 additionally facilitated membrane trafficking of ClC-2 channels. Interestingly, treatment with the Hsp90-targeting small molecule 17-allylamino-17-demethoxygeldanamycin (17-AAG) substantially boosted ClC-2 protein expression. Also, 17-AAG effectively increased both total and cell surface protein levels of leukodystrophy-causing loss-of-function ClC-2 mutant channels. Our findings highlight the therapeutic potential of 17-AAG in correcting anomalous ClC-2 proteostasis associated with leukodystrophy.  相似文献   

9.
Iron nanoparticles encapsulated by carbon are protected from reactions with their environment avoiding oxidation in ambient conditions and thus, preserving their magnetic properties. Such particles are good candidates for magnetic fluid hyperthermia. When graphite shells are present, acidic treatments allow the formation of carboxylic groups on the nanoparticle surface. Those carboxylic groups can be used for further complexation with the drug cisplatin. We show the possibility of loading cisplatin on such nanoparticles and that the loading is dependent on the degree of surface functionalization. The drug release is dependent on time and temperature, making it ideal for applications involving hyperthermia. We show the possibility of applying hyperthermia in vitro using these nanoparticles. When loaded with cisplatin a stronger cytotoxic effect is observed. Such particles could be potentially used as multimodal anti-cancer agents for therapies based on the synergistic effect of chemotherapy and hyperthermia.  相似文献   

10.
《Ceramics International》2019,45(12):15143-15155
Designing biocompatible superparamagnetic mesoporous nanoparticles for advanced healthcare applications has received much attention. In this research, we have synthesized intrinsic mesoporous superparamagnetic hydroxyapatite (HAp) nanoparticles using bio-waste of black Chlamys varia seashell as a calcium source by sodium dodecyl sulfate (SDS)–enabled microwave-assisted synthesis approach. The synthesized Fe-doped HAp nanoparticles were characterized using various characterization techniques to know the phase purity and morphological features. The incorporation of Fe greatly affected the morphology of HAp nanoparticles without affecting their crystalline phase. Superparamagnetic behavior was observed with the incorporation of Fe in the HAp nanoparticles. Further, saturation magnetization was enhanced with higher incorporation of Fe ions. The cytotoxicity studies of the synthesized pure and Fe-doped HAp samples conducted using a human osteoblasts cell line (MG63), which indicated that Fe-doped HAp nanoparticles are biocompatible. Further, antibacterial activity analysis also confirmed their excellent antibacterial performance against different pathogens. Hence, SDS-enabled microwave-assisted synthesis approach using seashell as a calcium source would be a better approach for the production of intrinsic mesoporous superparamagnetic HAp nanoparticles for various biomedical applications, such as drug targeting, hyperthermia cancer therapy, and magnetic resonance imaging.  相似文献   

11.
The present paper describes ordered alloy FePt nanoparticles with high magnetic susceptibility to alternate current (ac) fields at around room temperature for biomedical applications such as magnetic sensing devices for diagnostics and magnetic hyperthermia for cancer therapy. Since ac magnetic susceptibility takes the maximum value at a temperature near the blocking temperature of magnetic nanoparticles, the blocking temperature of the FePt nanoparticles is required to be adjusted at around room temperature to improve biomedical performances. Ordered alloy FePt has much higher magnetic anisotropy than iron oxides, and it can be the best candidate in the case of their particle size less than 10 nm. The ordered alloy FePt nanoparticles are synthesized by reduction of Fe and Pt organo-metallic compounds with tetraethylene glycol using poly(N-vinyl-2-pyrrolidone) (PVP) as a protective agent. PVP is a water-soluble polymer, and is proper to obtain dispersion into water. Influences of reaction temperature on crystallite size (particle size) and blocking temperature and the relationship between the blocking temperature and the value of ac magnetic susceptibility at around room temperature are investigated. Furthermore, PVP concentration at the synthesis to obtain well dispersed nanoparticle-suspension is examined.  相似文献   

12.
We report here on covalent functionalization of magnetic nanoparticle colloidal suspension (ferrofluid) with doxorubicin. Since doxorubicin (adriamycin) is a potent anti-cancer drug, such particles can be guided with external magnetic field to a target tissue, a carrier process that may overcome the non-specificity and efficiency of adriamycin as a drug. The nanoferrite functionalization was effected by means of acid chloride chemistry leading to the formation of covalent bond between the hydroxyl groups at the nanoparticle surface and acid chloride molecules. This procedure can be easily tailored to provide the nanoferrites with various functionalities capable of further modifications with, e.g., drug molecules. Thus, we used such modified nanoferrites to covalently attach molecules of anti-tumor drug—doxorubicin. The attachment was verified by means of FTIR and cyclic voltammetry. Mean size of nanoferrites was evaluated by powder X-ray diffraction (PXRD) technique and high-resolution field emission scanning electron microscope (HR-FESEM). The amount of doxorubicin attached to nanoparticles was assessed by means of quartz crystal microbalance combined with cyclic voltammetry.  相似文献   

13.
The goal of this study was to develop doxorubicin conjugate nanoparticles with increased antitumor effects, reduced side effects and the ability to overcome multidrug resistance (MDR). In this regard, folate‐decorated maleilated pullulan–doxorubicin conjugate nanoparticles were developed as carriers for co‐delivery of pyrrolidinedithiocarbamate and doxorubicin (FA‐MP‐DOX/PDTC + DOX NPs). The resultant nanoparticles showed spherical geometry, with an average diameter of 152 nm. The two drugs were released from the nanoparticles in a slow, pH‐dependent sustained release. To test the efficacy of these nanoparticles, in vitro tests including cell viability and folate receptor‐mediated endocytosis were conducted against both A2780 cells and A2780/DOXR cells. Compared to free DOX, the FA‐MP‐DOX/PDTC + DOX NPs showed effective but less potent cytotoxicity against A2780 cells. For A2780/DOXR cells, they showed enhanced cellular uptake, increased targeting capacity and cytotoxicity. These results suggest that co‐delivery of PDTC and DOX may further overcome MDR by transporting an increased amount of DOX within cells in addition to the folate receptor‐mediated endocytosis process. © 2012 Society of Chemical Industry  相似文献   

14.
Interest in utilizing magnetic nanoparticles for biomedical treatments originates from their external controllability of transportation and movement inside biological objects and magnetic heat generation. Advances in nanoparticle and nanotechnology enable us to produce magnetic nanoparticles of specific morphology and to engineer particle surfaces to manipulate their characteristics for specific applications. Intensive investigations and developments have been carried out in improving the quality of magnetic particles, regarding their size, shape, size distribution, their magnetism and their surface. The magnetic nanoparticles with appropriate surface chemistry can conjugate various biomaterials such as drugs, proteins, enzymes, antibodies, or nucleotides to be used for numerous in vivo applications including MRI contrast enhancement, immunoassay, hyperthermia, drug delivery, and cell separation. Here we review both the key technical principles of magnetic nanoparticle synthesis and the ongoing advancement of biomedical treatments using magnetic nanoparticles, specifically, the advancement in controlled drug delivery and hyperthermia.  相似文献   

15.
Iron oxide nanoparticle/Poly(ethylene terephthalate) (PET) nanowebs were obtained by electrospinning. To achieve superparamagnetic properties, iron oxide nanoparticles with diameters below 25 nm were used. Diameter distribution of iron oxide nanoparticles was measured by a particle size analyzer. Iron oxide nanoparticles were added into 16 wt % PET solution in the ratio of 5, 10, and 15 wt % to PET. The morphology of iron oxide nanoparticle/PET nanowebs was observed using field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The nanofiber diameter increased as increasing iron oxide nanoparticle concentration. The superparamagnetic behavior of iron oxide nanoparticle/PET nanofiber was confirmed using superconducting quantum interference device (SQUID). The degree of crystallinity of iron oxide nanoparticle/PET nanowebs was calculated from a differential scanning calorimeter (DSC) results. The change of flexural rigidity and tensile properties of electrospun iron oxide nanoparticle/PET nanowebs with the external magnetic field were examined ISO 9073-7 testing method, universal testing machine and an appropriate magnet. Also, the elastic modulus of iron oxide nanoparticle/PET nanofiber was measured using nanoindentation. With applying magnetic field, the improvement in mechanical properties of field-responsive magnetic nanofibers and nanowebs was confirmed. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012  相似文献   

16.
Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.  相似文献   

17.

Different phosphates and phosphonates have shown excellent coating ability toward magnetic nanoparticles, improving their stability and biocompatibility which enables their biomedical application. The magnetic hyperthermia efficiency of phosphates (IDP and IHP) and phosphonates (MDP and HEDP) coated Fe3O4 magnetic nanoparticles (MNPs) were evaluated in an alternating magnetic field. For a deeper understanding of hyperthermia, the behavior of investigated MNPs in the non-alternating magnetic field was monitored by measuring the transparency of the sample. To investigate their theranostic potential coated Fe3O4-MNPs were radiolabeled with radionuclide 177Lu. Phosphate coated MNPs were radiolabeled in high radiolabeling yield (>?99%) while phosphonate coated MNPs reached maximum radiolabeling yield of 78%. Regardless lower radiolabeling yield both radiolabeled phosphonate MNPs may be further purified reaching radiochemical purity of more than 95%. In vitro stabile radiolabeled nanoparticles in saline and HSA were obtained. The high heating ability of phosphates and phosphonates coated MNPs as sine qua non for efficient in vivo hyperthermia treatment and satisfactory radiolabeling yield justifies their further research in order to develop new theranostic agents.

  相似文献   

18.
Early detection and treatment of disease is the most important component of a favorable prognosis. Biomedical researchers have thus invested tremendous effort in improving imaging techniques and treatment methods. Over the past decade, concepts and tools derived from nanotechnology have been applied to overcome the problems of conventional techniques for advanced diagnosis and therapy. In particular, advances in nanoparticle technology have created new paradigms for theranostics, which is defined as the combination of therapeutic and diagnostic agents within a single platform. In this Account, we examine the potential advantages and opportunities afforded by magnetic nanoparticles as platform materials for theranostics. We begin with a brief overview of relevant magnetic parameters, such as saturation magnetization, coercivity, and magnetocrystalline anisotropy. Understanding the interplay of these parameters is critical for optimizing magnetic characteristics needed for effective imaging and therapeutics, which include magnetic resonance imaging (MRI) relaxivity, heat emission, and attractive forces. We then discuss approaches to constructing an MRI nanoparticle contrast agent with high sensitivity. We further introduce a new design concept for a fault-free contrast agent, which is a T1 and T2 dual mode hybrid. Important capabilities of magnetic nanoparticles are the external controllability of magnetic heat generation and magnetic attractive forces for the transportation and movement of biological objects. We show that these functions can be utilized not only for therapeutic hyperthermia of cancer but also for controlled release of cancer drugs through the application of an external magnetic field. Additionally, the use of magnetic nanoparticles to drive mechanical forces is demonstrated to be useful for molecular-level cell signaling and for controlling the ultimate fate of the cell. Finally, we show that targeted imaging and therapy are made possible by attaching a variety of imaging and therapeutic components. These added components include therapeutic genes (small interfering RNA, or siRNA), cancer-specific ligands, and optical reporting dyes. The wide range of accessible features of magnetic nanoparticles underscores their potential as the most promising platform material available for theranostics.  相似文献   

19.
In this research a novel controlled anticancer drug delivery system with dual pH and thermal responses was designed based on magnetic mesoporous silica nanoparticles that were anchored by β-cyclodextrin and coated by poly(N-isopropylacrylamide) (PNIPAM). Results demonstrated that the behavior of doxorubicin (anticancer drug) release depended on pH and temperature conditions. At endosomal pH (pH 5.5) the amount of drug release enhanced because the cap was removed from the pores. Furthermore, PNIPAM shell collapsed above the lower critical solution temperature and the releasing of drug increased. Thus, this nanocarrier would have the potential to be applied in the tumor therapy.  相似文献   

20.
Electrospinning is a very versatile and efficient method of fabricating nanofibers with the desired properties. Polyvinylpyrrolidone (PVP) in ethanol solution was electrospun into nanofibers and used as a precursor for the preparation of carbon nanofibers. Cobalt chloride was also incorporated with PVP nanofibers to produce carbon nanofiber composites with enhanced electrical conductivity and electrochemical properties. The surface morphology and physical properties of the electrospun nanofibers, carbonized nanofibers, and their composites were observed by scanning electron microscopy, transmission electron microscopy, and X‐ray diffraction. The electrochemical behavior of the carbon nanofiber composites was studied by drop‐casting on a working surface of the screen‐printed carbon electrode and examined by cyclic voltammetry and electrochemical impedance spectroscopy. The results indicated that carbon nanofiber composites were decorated with cobalt nanoparticles and enhanced the charge‐transfer efficiency on the electrode surface. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45639.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号-23

京公网安备 11010802026262号