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1.
以甲基丙烯酸羟乙酯(HEMA)和甲基丙烯酸(MAA)为聚合单体,异辛烷为分散介质,Span80和Tween80为复配乳化剂,采用反相微乳液聚合法制得不同单体配比的聚(甲基丙烯酸羟乙酯-co-甲基丙烯酸)(P(HEMA-co-MAA))纳米凝胶。确定了产物的pKa值及实际单体物质的量比,对产物的形貌进行了表征并研究了产物的pH响应性.结果显示,MAA物质的量分数为20%的纳米凝胶的pKa值为5.83,在pH=3和pH=7时其数均粒径分别为48 nm和90 nm;当环境pH接近pKa值时,纳米凝胶分散液的浊度明显降低,溶胀率明显上升,表观黏度急剧增加,说明纳米凝胶具有良好的pH响应性。  相似文献   

2.
Multifunctional and thermosensitive poly(N-isopropylacrylamide-co-propyl acrylic acid-co-hydroxyethyl methacrylate) (P(NIPAAm-co-PAAc-co-HEMA)) nanogels were prepared by miniemulsion polymerization. The mean sizes of the nanogels measured by dynamic light scattering (DLS) varied from 120 to 400?nm with an increase in temperature. Transmission electron microscopy (TEM) showed that the nanogels displayed well-dispersed spherical morphology. The nanogels were conjugated by human transferrin (Tf) and the coupling of transferrin molecules with nanogels was verified by UV-vis spectroscopy. The?cytotoxicity study indicated that the nanogels did not exhibit apparent cytotoxicity. Fluorescence spectroscopy analysis as well as confocal laser scanning microscopy (CLSM) was used to confirm that the Tf-conjugated nanogels could specifically bind to A549 tumor cells. In addition, the Tf-conjugated nanogels loaded with Doxorubicin (Dox) could efficiently release the drug inside the cell, suggesting that the Tf-conjugated nanogels are useful drug carriers for tumor cell targeting.  相似文献   

3.
Polyethylene glycol-polyethylenimine (PEG-PEI) nanogels have been used to deliver nucleic acids and oligonucleotides into cells. First, we synthesized PEG-PEI nanogels with methylene proton ratios (CH2O:CH2N) in PEG-PEI ranging from approximately 6.8:1 to 4:1 and less, as shown by 1H NMR spectra. We first synthesized various nanogels with varying ratios of CH2O:CH2N (methylene proton) in PEG-PEI as shown by 1H NMR spectra and tested their cytotoxicity using a rodent pancreatic adenocarcinoma cell line (Pan 02). We showed that the nanogel PEG-PEI with methylene proton ratio of 4:1 was strongly cytotoxic to Pan 02 cells in vitro, while the nanogel with the methylene proton ratio of 6.8:1 was not toxic. We incorporated a novel anti-cancer drug, 6-(hydroxymethyl)-1,4-anthracenedione (AQ) analogue (AQ10) into nontoxic nanogel PEG-PEI and tested the effect of AQ10 loaded nanogel PEG-PEI (AQ10-nanogel PEG-PEI) and AQ10 dissolved in DMSO on Pan 02 cell growth. The size of this AQ10-nanogel PEG-PEI was characterized using atomic force microscopy (AFM). Our studies showed that the AQ10-nanogel PEG-PEI is readily taken up by Pan 02 cells. Growth attenuation of Pan 02 cells treated with AQ10-nanogel PEG-PEI was three to four times that of cells treated with AQ10 dissolved in DMSO. These results suggest that PEG-PEI, usually used to deliver nucleic acids into cells, can also be used to deliver an insoluble small molecule anticancer drug, AQ10.  相似文献   

4.
The copolymer nanogels composed of two N-substituted acrylamides with different water solubility, N-isopropylacrylamide (NIPAM, water-soluble) and N-t-butylacrylamide (TBAM, water-insoluble), were prepared by free-radical polymerization in the presence of sodium dodecyl sulfate (SDS) as a dispersant and found to exhibit thermogelling ability at very low concentrations. To investigate the structure of the P(NIPAM-TBAM) nanogel and its formation mechanism in dispersion polymerization, we prepared the nanogels by changing the conditioning time, which is the time between the addition of SDS to the monomer solution and the start of polymerization, and compared the thermogelling properties of the resultant nanogels. As the conditioning time increased, (i) the hydrodynamic diameter of the nanogel decreased, (ii) the sol–gel and gel-syneresis transition temperatures of the nanogel dispersion decreased, and (iii) the storage moduli of the nanogel dispersion in a gel state increased. These results indicate that the P(NIPAM-TBAM) nanogel has a block-like structure composed of the TBAM-rich brushes and the NIPAM-rich core with three-dimensional polymer network, and that the TBAM ratio in the brushes increases with an increase in the conditioning time. It should be noted that the critical gelation concentration of the P(NIPAM-TBAM) nanogel dispersion was very low (~1.3 wt%), compared with other thermogelling polymers reported in literatures. This low gelation concentration can be attributed to the gel structure of the nanogel core because the NIPAM-rich core can retain water inside even when the TBAM-rich brushes are dehydrated and crosslink with each other to induce gelation of the system.  相似文献   

5.
Allyl-PEG capped inorganic NPs, including magnetic iron oxide (IONPs), fluorescent CdSe/ZnS quantum dots (QDs), and metallic gold (AuNPs of 5 and 10 nm) both individually and in combination, were covalently attached to pH-responsive poly(2-vinylpyridine-co-divinylbenzene) nanogels via a facile and robust one-step surfactant-free emulsion polymerization procedure. Control of the NPs associated to the nanogels was achieved by the late injection of the NPs to the polymerization solution at a stage when just polymeric radicals were present. Remarkably, by varying the total amount of NPs injected, the swelling behavior could be affected. Furthermore, the magnetic response as well as the optical features of the nanogels containing either IONPs or QDs could be modified. In addition, a radical quenching in case of gold nanoparticles was observed, thus affecting the final nanogel geometry.  相似文献   

6.
We have developed sparsely cross-linked "nanogels", subcolloidal polymer structures composed of covalently linked, linear polyacrylamide chains, as novel replaceable DNA sequencing matrixes for capillary and microchip electrophoresis. Nanogels were synthesized via inverse emulsion (water-in-oil) copolymerization of acrylamide and a low percentage (approximately 10(-4) mol %) of N,N-methylene bisacrylamide (Bis). Nanogels and nanogel networks were characterized by multiangle laser light scattering and rheometry, respectively, and tested for DNA sequencing in both capillaries and chips with four-color LIF detection. Typical nanogels have an average radius of approximately 230 nm, with approximately 75% of chains incorporating a Bis cross-linker. The properties and performance of nanogel matrixes are compared here to those of a linear polyacrylamide (LPA) network, matched for both polymer weight-average molar mass (M(w)) and the extent of interchain entanglements (c/c). At sequencing concentrations, the two matrixes have similar flow characteristics, important for capillary and microchip loading. However, because of the physical network stability provided by the internally cross-linked structure of the nanogels, substantially longer average read lengths are obtained under standard conditions with the nanogel matrix at a 98.5% accuracy of base-calling (for CE: 680 bases, an 18.7% improvement over LPA, with the best reads as long as 726 bases, compared to 568 bases for the LPA matrix). We further investigated the use of the nanogel matrixes in a high-throughput microfabricated DNA sequencing device consists of 96 separation channels densely fabricated on a 6-in. glass wafer. Again, preliminary DNA sequencing results show that the nanogel matrixes are capable of delivering significantly longer average read length, compared to an LPA matrix of comparable properties. Moreover, nanogel matrixes require 30% less polymer per unit volume than LPA. The addition of a small amount of low molar mass LPA or ultrahigh molar mass LPA to the optimized nanogel sequencing matrix further improves read length as well as the reproducibility of read length (RSD < 1.6%). This is the first report of a replaceable DNA sequencing matrix that provides better performance than LPA, in a side-by-side comparison of polymer matrixes appropriately matched for molar mass and the extent of interchain entanglements. These results could have significant implications for the improvement of microchip-based DNA sequencing technology.  相似文献   

7.
Poly(acrylic acid) (PAA) nanogels with a hollow core-porous shell structure were prepared by the direct polymerization of an acrylic acid monomer in the presence of hydroxypropylcellulose (HPC) and a cross-linking agent, N,N-methylenebisacrylamide, followed by removal of HPC from the generated HPC-PAA nanoparticles in a basic environment. The properties of PAA nanogel were characterized by dynamic light scattering, FT-IR, transmission electron microscopy, and atomic force microscopy. It is found that the nanogels have a hollow core-porous shell structure. Protein, bovine serum albumin (BSA), and an antitumor agent, doxorubicin hydrochloride, were used as model drugs to investigate their loading abilities as versatile drug-delivery vehicles. The nanogel exhibits surprisingly high loading ability to both protein and small molecular drugs. For example, the maximum BSA loading capacity of PAA nanogel can reach as high as 800% (i.e., 1 mg of nanogel can load about 8.0 mg of BSA). This high loading capacity may be related with the hollow core-porous shell structure of PAA nanogels. PAA nanogels have also shown sustained drug release properties and can cross biological barriers to deliver loaded cargo inside cells. Considering the high stability of the materials, simple and mild preparation procedure, high loading capacity, sustained-release property, and ability to protect biological agents from denaturation, PAA nanogels should be promising drug-delivery carriers for drug-delivery systems.  相似文献   

8.
Specific detection of protein biomarkers plays an important role in diagnostics and therapeutics. We have fabricated polymeric nanogels, which can specifically interact with the cancer biomarker thrombin to serve as a model. Two types of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers bearing a thrombin-binding oligonucleotide aptamer and its complementary chain were independently synthesized by redox-initiated radical polymerization. These MPC polymers associate in a complimentary fashion due to double strand formation of the oligonucleotides in aqueous media, leading to the spontaneous formation of spherical nanogels. Nanogel formation was confirmed by dynamic light scattering (DLS) and transmittance microscopy. The average size of nanogel particles was 124 ± 2 nm and the nanogels were mono-dispersed (polydispersity index 0.21). Functional intercalators could be stably incorporated into nanogels through the physical interaction between the intercalators and the oligonucleotides. The ethidium bromide (EtBr)-incorporating nanogels were used as detectors for thrombin. The fluorescence intensity of solutions containing the EtBr-incorporating nanogels was decreased with an increase in the concentration of thrombin. The transformation of quadruplex–thrombin structure from complementary double-stranded structures resulted in the decrease in fluorescence intensity. In contrast, the intensity did not change when the nanogels were incubated with albumin. Thrombin is only one such model used to demonstrate this technique; oligonucleotide aptamers can be freely designed to interact with versatile bio-substances. Therefore, aptamer-crosslinked nanogels can be appropriate nanomaterials for disease diagnosis and therapy.  相似文献   

9.
Nanoparticles degradable upon external stimuli combine pharmacokinetic features of both small molecules as well as large nanoparticles. However, despite promising preclinical results, several redox responsive disulphide‐linked nanoparticles failed in clinical translation, mainly due to their unexpected in vivo behavior. Glutathione (GSH) is one of the most evaluated antioxidants responsible for disulfide degradation. Herein, the impact of GSH on the in vivo behavior of redox‐sensitive nanogels under physiological and modulated conditions is investigated. Labelling of nanogels with a DNA‐intercalating dye and a radioisotope allows visualization of the redox responsiveness at the cellular and the systemic levels, respectively. In vitro, efficient cleavage of disulphide bonds of nanogels is achieved by manipulation of intracellular GSH concentration. While in vivo, the redox‐sensitive nanogels undergo, to a certain extent, premature degradation in circulation leading to rapid renal elimination. This instability is modulated by transient inhibition of GSH synthesis with buthioninsulfoximin. Altered GSH concentration significantly changes the in vivo pharmacokinetics. Lower GSH results in higher elimination half‐life and altered biodistribution of the nanogels with a different metabolite profile. These data provide strong evidence that decreased nanogel degradation in blood circulation can limit the risk of premature drug release and enhance circulation half‐life of the nanogel.  相似文献   

10.
Poly(N-isopropylacrylamide) (PNIPAM) nanogels were synthesized by emulsion polymerization using sodium dodecyl sulfate (SDS). After removal of SDS by dialysis, the surface tensions of the PNIPAM nanogel aqueous dispersions were measured at various temperatures by the pendant-drop method, and it was found that the surface tensions of the nanogel dispersion below the lower critical solution temperature (LCST) of PNIPAM were much smaller than those of water and comparable to those of the SDS aqueous solution. The stability of the aqueous foams generated by nitrogen bubbling thorough the PNIPAM nanogel dispersion was investigated below and above the LCST of PNIPAM. The foam prepared below the LCST was stable in some degree, whereas almost no foam was formed above the LCST. Moreover, the foam prepared below the LCST was quickly collapsed by changing the temperature above the LCST. This rapid defoaming represents that the surface activity of the PNIPAM nanogel can be switched off by the temperature increase across the LCST.  相似文献   

11.
Owing to their highly desirable properties that combine the properties of both hydrogels and nanomaterials, smart nanogels own great potentials as active nanocarriers in medical applications. In this paper, thermo-responsive nanogels with uniform sizes less than 50 nm in diameter were synthesized using potassium persulfate (KPS)/N,N,N′,N′-tetramethylethylenediamine (TMEDA) as a initiator system via a facile surfactant-free precipitation radical polymerization of N-isopropylacrylamide (NIPAM) at room temperature. Both transmission electron microscopy and dynamic light scattering were used to characterize the morphologies and diameters of the PNIPAM nanogels. All nanogels with spherical shape exhibited a narrow size distribution, and the finest nanogels were 43 nm in diameter on average. The very fine and highly pure nanogels would be more promising for drug delivery carriers than the bulk gels or microgels.  相似文献   

12.
在水相体系中进行葡聚糖与环氧氯丙烷的交联反应,FT-IR、TEM和SLS测试表明,制备出的葡聚糖粒子为醚键交联的、粒径数百纳米的窄粒径分布球形纳凝胶。SLS测试表明,凝胶粒子的粒径随葡聚糖浓度增大而增大,质量浓度为1.25 g/L、4.50 g/L、10.0 g/L的葡聚糖所制备的凝胶粒子平均粒径分别为119.5 nm3、54.0 nm1、526.8 nm;此外,借助DSC、RI和UV-Vis等测试研究了葡聚糖纳凝胶的相转变行为,结果表明,升温促使纳凝胶先收缩后溶胀;pH值升高引起纳凝胶亲水性下降,粒子收缩。  相似文献   

13.
A simple method of synthesizing hybrid silver–polyacrylic acid–poly(N-vinylpyrrolidone) (Ag–PAA–PVP) nanogels was demonstrated through in situ reducing Ag+ inside PAA–PVP nanogels, which were formed by polymerization of acrylic acid in the PVP solution. Due to the ion exchange between Ag+ and acid protons of PAA, stable Ag+ clusters were formed inside the PAA–PVP nanogels, and hybrid nanogels were obtained by reducing Ag+ by ascorbic acid. Transmission electronic microscopic (TEM) images clearly showed the existence of silver nanoparticles inside the Ag–PAA–PVP nanogels. These hybrid nanogels showed typical surface plasma resonance absorption peak around 420 nm, and the size of the silver nanoparticles inside the Ag–PAA–PVP nanogels could be controlled from 9.5 ± 1.6 nm to 1.9 ± 0.4 nm by increasing the feeding amount of Ag+. In addition, these hybrid nanogels showed photoluminescent properties in fluorescent spectra. Considering the pH sensitive property of these hybrid nanogels, they will have potential application in drug delivery and biomedical imaging systems.  相似文献   

14.
Magnetic, pH and temperature-sensitive, poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites with fluorescent properties were synthesized by free radical copolymerization-cross linking of NIPAM, N,N-dimethylaminoethyl methacrylate (DMAEMA) and 4-acrylamidofluorescein (AFA). The model anti-cancer drug, cisplatin (CDDP), was loaded into the resulted nanogel. For the production of CDDP-loaded nanocomposite, Fe3O4 magnetic nanoparticles (MNPs) and CDDP were loaded into the nanogel. Field-emission scanning electron microscopy (FE-SEM) indicated that the size of nanogel and CDDP-loaded nanocomposite were about 90 and 160?nm, respectively. The encapsulation efficiency of CCDP was found up to 65%. The loaded CCDP showed sustained thermal and pH-responsive drug release. A high level of drug release was observed under the conditions of low pH and high temperature. The lower critical solution temperature (LCST) of synthesized nanogel was about 40?°C. CDDP-loaded nanocomposite showed a volume phase transition from 282 to 128?nm at its LCST. Accordingly, in this study, the synthesized nanocomposite can be employed as a stimuli-responsive anti-cancer drug delivery system and the pH and temperature of solution have the potential to monitor the drug release.  相似文献   

15.
Surfaces that resist protein adsorption are important for many bioanalytical applications. Bovine serum albumin (BSA) coatings and multi-arm poly(ethylene glycol) (PEG) coatings display low levels of non-specific protein adsorption and have enabled highly quantitative single-molecule (SM) protein studies. Recently, a method was developed for coating a glass with PEG–BSA nanogels, a promising hybrid of these two low-background coatings. We characterized the nanogel coating to determine its suitability for SM protein experiments. SM adsorption counting revealed that nanogel-coated surfaces exhibit lower protein adsorption than covalently coupled BSA surfaces and monolayers of multi-arm PEG, so this surface displays one of the lowest degrees of protein adsorption yet observed. Additionally, the nanogel coating was resistant to DNA adsorption, underscoring the utility of the coating across a variety of SM experiments. The nanogel coating was found to be compatible with surfactants, whereas the BSA coating was not. Finally, applying the coating to a real-world study, we found that single ligand molecules could be tethered to this surface and detected with high sensitivity and specificity by a digital immunoassay. These results suggest that PEG–BSA nanogel coatings will be highly useful for the SM analysis of proteins.  相似文献   

16.
Smart drug delivery system of core–shell-type polypeptide nanogel of poly(Z-l-lysine-co-l-cystine) (PLL-LC) has been synthesized, which showed high drug loading content (DLC 16.5%) of DOX and pHe–glutathione (GSH) stepwise responsive disassembly. Modifying the shell of the nanogel by 2,3-dimethylmaleic anhydride (DMA) makes it quickly respond to the weak acidic tumor microenvironment (pHe 6.8–6.5), inducing the surface charge reversal and promoting the nanogel efficient uptake by cancer cells. Next, the nanogel can release encapsulated DOX in cytoplasm in the presence of high level of GSH therein via reduction and disassembly of the nanogel, resulting in highly selective cytotoxicity. MTT studies reveal the good biocompatibility of the nanogel before charge reversal and an efficient toxicity to cell under pHe microenvironment. In vitro experiments confirm the smart stepwise degradability of the nanogel and efficient therapy ability to cancer cell, indicating the nanogel is a potential drug delivery system.  相似文献   

17.
Drug delivery devices based on nanocomposite membranes containing thermoresponsive nanogels and superparamagnetic nanoparticles have been demonstrated to provide reversible, on-off drug release upon application (and removal) of an oscillating magnetic field. We show that the dose of drug delivered across the membrane can be tuned by engineering the phase transition temperature of the nanogel, the loading density of nanogels in the membrane, and the membrane thickness, allowing for on-state delivery of model drugs over at least 2 orders of magnitude (0.1-10 μg/h). The zero-order kinetics of drug release across the membranes permit drug doses from a specific device to be tuned according to the duration of the magnetic field. Drugs over a broad range of molecular weights (500-40000 Da) can be delivered by the same membrane device. Membrane-to-membrane and cycle-to-cycle reproducibility is demonstrated, suggesting the general utility of these membranes for drug delivery.  相似文献   

18.
In this work, we developed biodegradable chitin nanogels (CNGs) by controlled regeneration method. For multifunctionalization, we have conjugated CNGs with MPA-capped-CdTe-QDs (QD-CNGs) for the in vitro cellular localization studies. In addition, the Bovine Serum Albumin (BSA) was loaded on to QD-CNGs (BSA-QD-CNGs). The CNGs, QD-CNGs, and BSA-QD-CNGs were well-characterized by SEM and AFM, which shows that the nanogels are in the range of <100 nm. These were further characterized by FT-IR and Cyclic Voltametry. The cytocompatibility assay showed that the nanogels are nontoxic to L929, NIH-3T3, KB, MCF-7, PC3, and VERO cells. The cell uptake studies of the QD-CNGs were analyzed, which showed retention of these nanogels inside the cells (L929, PC3, and VERO). In addition, the protein loading efficiency of the nano gels has also been analyzed. Our preliminary studies reveal that these multifunctionalized nanogels could be useful for drug delivery with simultaneous imaging and biosensing.  相似文献   

19.
This study aimed to develop of a rapid and effective method to occlude dentinal tubules using carboxymethyl chitosan and lysozyme (CMC/LYZ) nanogels with encapsulated amorphous calcium phosphate (ACP) based on the transformation of ACP to HAP. In this work, CMC/LYZ was used to stabilize ACP and form CMC/LYZ-ACP nanogels, and then the nanogel-encapsulated ACP was applied to exposed dentinal tubule surfaces. The morphology of the nanogels was examined by transmission electron microscopy (TEM). Distribution and quantity of elements in CMC/LYZ-ACP nanogels were determined by element mapping and energy dispersive X-Ray spectroscopy (EDX). Scanning electron microscopy (SEM) images, XRD measurements and nanoindentation were applied to check the efficacy of tubular occlusion. TEM revealed that CMC/LYZ-ACP nanogels were spherical dense gel particles with size approximately 50–500?nm. Element mapping and EDX indicated that C, N, O, Ca, P, and S in the microspheres are thoroughly represented. SEM images shows that the thickness of the coating layer was approximately 1–2?μm and the depth to which the mineralized substance enters the dentinal tubule was approximately 4–8?μm. XRD measurements and nanoindentation indicated that the occluding mineralized substance observed were similar to nature dentin. CMC can form spherical dense nanogels loaded with ACP under the participation of lysozyme. The CMC/LYZ-ACP nanogels could increase the dentinal tubule occluding effectiveness. These results indicated that finding and developing novel nanomaterials of CMC/LYZ-ACP would be an effective strategy for the treatment of dentin hypersensitivity.  相似文献   

20.
In this study, a networked swellable dextrin nanogel (DNG) was developed to achieve stimulated responsive small interfering RNA (siRNA) release for melanoma tumor therapy. siRNA was loaded into multidimensional dextrin nanogels by charge condensation with positive arginine residues modified in the dextrin backbone. Moreover, the networked nanogel was destroyed and loosened based on its bioreducible responsive property to control accelerated siRNA release in a bioreducible intracellular environment, while it remained stable under normal physiological conditions. We demonstrated that DNGs had swellable and disassembly properties under reduced buffer condition by transmission electron microscopy evaluation. The DNGs achieved an endosomal escape followed by selective release of the cargo into the cytosol by glutathione-triggered disassembly according to confocal microscopy observation. Thus, this smart nanogel achieved outstanding luciferase gene silencing efficiency and decreased Bcl2 protein expression in vitro and in vivo based on western blot analysis. Moreover, this nanogel exhibited superior anti-tumor activity for B16F10 xenograft tumors in C57BL/6 mice. These results demonstrate that the networked DNGs are effective for gene condensation and controlled intracellular release for tumor therapy. Overall, these findings suggest that this multidimensional swellable stimuli-responsive dextrin nanogel is an innovative strategy with great promise for gene and drug delivery.
  相似文献   

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