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1.
Monodisperse silica‐coated manganese oxide nanoparticles (NPs) with a diameter of ~35 nm are synthesized and are aminated through silanization. The amine‐functionalized core–shell NPs enable the covalent conjugation of a fluorescent dye, Rhodamine B isothiocyanate (RBITC), and folate (FA) onto their surface. The formed Mn3O4@SiO2(RBITC)–FA core–shell nanocomposites are water‐dispersible, stable, and biocompatible when the Mn concentration is below 50 µg mL?1 as confirmed by a cytotoxicity assay. Relaxivity measurements show that the core–shell NPs have a T1 relaxivity (r1) of 0.50 mM ?1 s?1 on the 0.5 T scanner and 0.47 mM ?1 s?1 on the 3.0 T scanner, suggesting the possibility of using the particles as a T1 contrast agent. Combined flow cytometry, confocal microscopy, and magnetic resonance imaging studies show that the Mn3O4@SiO2(RBITC)–FA nanocomposites can specifically target cancer cells overexpressing FA receptors (FARs). Findings from this study suggest that the silica‐coated Mn3O4 core–shell NPs could be used as a platform for bimodal imaging (both magnetic resonance and fluorescence) in various biological systems.  相似文献   

2.
Monodisperse iron oxide/microporous silica core/shell composite nanoparticles, core(γ‐Fe2O3)/shell(SiO2), with a diameter of approximately 100 nm and a high magnetization are synthesized by combining sol–gel chemistry and supercritical fluid technology. This one‐step processing method, which is easily scalable, allows quick fabrication of materials with controlled properties and in high yield. The particles have a specific magnetic moment (per kg of iron) comparable to that of the bulk maghemite and show superparamagnetic behavior at room temperature. The nanocomposites are proven to be useful as T2 MRI imaging agent. They also have potential to be used in NMR proximity sensing, theranostic drug delivery, and bioseparation.  相似文献   

3.
A multifunctional nanoscale platform that is self‐assembled from a hydrophobic poly( dl ‐lactide‐coglycolide)(PLGA) core and a hydrophilic paramagnetic‐folate‐coated PEGylated lipid shell (PFPL; PEG=polyethylene glycol) is designed for simultaneous magnetic resonance imaging (MRI) and targeted therapeutics. The nanocomplex has a well‐defined core‐shell structure which is studied using confocal laser scanning microscopy (CLSM). The paramagnetic diethylenetriaminepentaacetic acid‐gadolinium (DTPA‐Gd) chelated to the shell layer exhibits significantly higher spin–lattice relaxivity (r1) than the clinically used small‐molecular‐weight MRI contrast agent Magnevist®. The PLGA core serves as a nanocontainer to load and release the hydrophobic drugs. From a drug‐release study, it is found that the modification of the PLGA core with a polymeric liposome shell can be a useful tool for reducing the drug‐release rate. Cellular uptake of folate nanocomplex is found to be higher than that of non‐folate‐nanocomplex due to the folate‐binding effect on the cell membrane. This work indicates that the multifunctional platform with combined characteristics applicable to MRI and drug delivery may have great potential in cancer chemotherapy and diagnosis.  相似文献   

4.
A simple and efficient method for synthesizing a range of hybrid nanocomposites based on a core of silica nanospheres (160, 330, and 660 nm in diameter) covered by an outer shell of superparamagnetic nanoparticles, either iron oxide or heterodimeric FePt‐iron oxide nanocrystals, is presented. The magnetic and ultrasound characterization of the resulting nanocomposites shows that they have great potential as contrast agents for dual‐mode imaging purposes, combining magnetic resonance imaging (MRI) and ultrasonography (US).  相似文献   

5.
The synthesis (by a facile two‐step sol–gel process), characterization, and application in controlled drug release is reported for monodisperse core–shell‐structured Fe3O4@nSiO2@mSiO2@NaYF4: Yb3+, Er3+/Tm3+ nanocomposites with mesoporous, up‐conversion luminescent, and magnetic properties. The nanocomposites show typical ordered mesoporous characteristics and a monodisperse spherical morphology with narrow size distribution (around 80 nm). In addition, they exhibit high magnetization (38.0 emu g?1, thus it is possible for drug targeting under a foreign magnetic field) and unique up‐conversion emission (green for Yb3+/Er3+ and blue for Yb3+/Tm3+) under 980 nm laser excitation even after loading with drug molecules. Drug release tests suggest that the multifunctional nanocomposites have a controlled drug release property. Interestingly, the up‐conversion emission intensity of the multifunctional carrier increases with the released amount of model drug, thus allowing the release process to be monitored and tracked by the change of photoluminescence intensity. This composite can act as a multifunctional drug carrier system, which can realize the targeting and monitoring of drugs simultaneously.  相似文献   

6.
Surfactant‐free, self‐assembled iron oxide/silica core–shell (SAIO@SiO2) nanocarriers were synthesized as bifunctional magnetic vectors that can be triggered for the controlled release of therapeutic agents by an external magnetic field. In addition, drug release profiles can be well‐regulated through an ultrathin layer of silica shell. The hydrophobic drug molecules were encapsulated within the iron oxide‐PVA core and then further covered with a thin‐layer silica shell to regulate the release pattern. Remote control of drug release from the SAIO@SiO2 nanocarriers was achieved successfully using an external magnetic field where the core phase being structurally disintegrated to a certain extent while subjected to magnetic stimulus, resulting in a burst release of the encapsulated drug. However, a relatively slow and linear release restored immediately, directly after removal of the stimulus. The nanostructural evolution of the nanocarriers upon the stimulus was examined and the mechanism for controlled drug release is proposed for such a core–shell nanocarrier. Surprisingly, the surfactant‐free SAIO@SiO2 nanocarriers demonstrated a relatively high uptake efficiency from the HeLa cell line. Together with a well‐regulated controlled release design, the nanocarriers may provide great advantages as an effective cell‐based drug delivery nanosystem for biomedical applications.  相似文献   

7.
Development of multifunctional nanoscale coordination polymers (NCPs) allowing for T1‐ and T2‐weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, nanoscale coordination polymers (NCPs) with a diameter of ≈80 nm are obtained with 1,1′‐dicarboxyl ferrocene (Fc) as building blocks and magnetic gadolinium(III) ions as metallic nodes using a nanoprecipitation method, then further aminated through silanization. The amine‐functionalized Fc‐Gd@SiO2 NCPs enable the covalent conjugation of a fluorescent rhodamine dye (RBITC) and an arginine‐glycine‐aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed water‐dispersible Fc‐Gd@SiO2(RBITC)–RGD NCPs exhibit a low cytotoxicity, as confirmed by MTT assay. They have a longitudinal relaxivity (r1) of 5.1 mM?1 s?1 and transversal relaxivity (r2) of 21.7 mM?1 s?1, suggesting their possible use as both T1‐positive and T2‐negative contrast agents. In vivo MR imaging experiments show that the signal of tumor over‐expressing high affinity αvβ3 integrin from T1‐weighted MR imaging is positively enhanced 47±5%, and negatively decreased 33±5% from T2‐weighted MR imaging after intravenous injection of Fc‐Gd@SiO2(RBITC)–RGD NCPs.  相似文献   

8.
Construction of multifunctional stimuli‐responsive nanosystems intelligently responsive to inner physiological and/or external irradiations based on nanobiotechnology can enable the on‐demand drug release and improved diagnostic imaging to mitigate the side‐effects of anticancer drugs and enhance the diagnostic/therapeutic outcome simultaneously. Here, a triple‐functional stimuli‐responsive nanosystem based on the co‐integration of superparamagnetic Fe3O4 and paramagnetic MnOx nanoparticles (NPs) onto exfoliated graphene oxide (GO) nanosheets by a novel and efficient double redox strategy (DRS) is reported. Aromatic anticancer drug molecules can interact with GO nanosheets through supramolecular π stacking to achieve high drug loading capacity and pH‐responsive drug releasing performance. The integrated MnOx NPs can disintegrate in mild acidic and reduction environment to realize the highly efficient pH‐responsive and reduction‐triggered T1‐weighted magnetic resonance imaging (MRI). Superparamagnetic Fe3O4 NPs can not only function as the T2‐weighted contrast agents for MRI, but also response to the external magnetic field for magnetic hyperthermia against cancer. Importantly, the constructed biocompatible GO‐based nanoplatform can inhibit the metastasis of cancer cells by downregulating the expression of metastasis‐related proteins, and anticancer drug‐loaded carrier can significantly reverse the multidrug resistance (MDR) of cancer cells.  相似文献   

9.
A novel multifunctional drug‐delivery platform is developed based on cholesteryl succinyl silane (CSS) nanomicelles loaded with doxorubicin, Fe3O4 magnetic nanoparticles, and gold nanoshells (CDF‐Au‐shell nanomicelles) to combine magnetic resonance (MR) imaging, magnetic‐targeted drug delivery, light‐triggered drug release, and photothermal therapy. The nanomicelles show improved drug‐encapsulation efficiency and loading level, and a good response to magnetic fields, even after the formation of the gold nanoshell. An enhancement for T2‐weighted MR imaging is observed for the CDF‐Au‐shell nanomicelles. These nanomicelles display surface plasmon absorbance in the near‐infrared (NIR) region, thus exhibiting an NIR (808 nm)‐induced temperature elevation and an NIR light‐triggered and stepwise release behavior of doxorubicin due to the unique characteristics of the CSS nanomicelles. Photothermal cytotoxicity in vitro confirms that the CDF‐Au‐shell nanomicelles cause cell death through photothermal effects only under NIR laser irradiation. Cancer cells incubated with CDF‐Au‐shell nanomicelles show a significant decrease in cell viability only in the presence of both NIR irradiation and a magnetic field, which is attributed to the synergetic effects of the magnetic‐field‐guided drug delivery and the photothermal therapy. Therefore, such multicomponent nanomicelles can be developed as a smart and promising nanosystem that integrates multiple capabilities for effective cancer diagnosis and therapy.  相似文献   

10.
A programmed drug‐delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core–shell‐based “nanodepot” consisting of a liposomal core and a crosslinked‐gel shell (designated Gelipo) is developed for the sequential and site‐specific delivery (SSSD) of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and doxorubicin (Dox). As a small‐molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half‐maximal inhibitory concentration (IC50) of TRAIL and Dox co‐loaded Gelipo (TRAIL/Dox‐Gelipo) toward human breast cancer (MDA‐MB‐231) cells is 83 ng mL–1 (Dox concentration), which presents a 5.9‐fold increase in the cytotoxicity compared to 569 ng mL–1 of Dox‐loaded Gelipo (Dox‐Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA‐MB‐231 xenograft tumor animal model.  相似文献   

11.
Robust, amphiphilic core–shell nanoparticles that are selectively labeled with gadolinium in the hydrophilic and water‐swollen shell layer are depicted in the cover picture. These well‐defined nanostructured materials exhibit high relaxivity, a large loading capacity, and are based upon a biocompatible platform for ultimate function in magnetic resonance imaging (MRI) applications, as reported by Wooley and co‐workers on p. 1248. Shell‐crosslinked knedel‐like nanoparticles (SCKs; “knedel” is a Polish term for dumplings) were derivatized with gadolinium chelates and studied as robust magnetic‐resonance‐imaging‐active structures with hydrodynamic diameters of 40 ± 3 nm. SCKs possessing an amphiphilic core–shell morphology were produced from the aqueous assembly of diblock copolymers of poly‐(acrylic acid) (PAA) and poly(methyl acrylate) (PMA), PAA52b–PMA128, and subsequent covalent crosslinking by amidation upon reaction with 2,2′‐(ethylenedioxy)bis(ethylamine) throughout the shell layer. The properties of these materials, including non‐toxicity towards mammalian cells, non‐immunogenicity within mice, and capability for polyvalent targeting, make them ideal candidates for utilization within biological systems. The synthesis of SCKs derivatized with GdIII and designed for potential use as a unique nanometer‐scale contrast agent for MRI applications is described herein. Utilization of an amino‐functionalized diethylenetriaminepentaacetic acid–Gd analogue allowed for direct covalent conjugation throughout the hydrophilic shell layer of the SCKs and served to increase the rotational correlation lifetime of the Gd. In addition, the highly hydrated nature of the shell layer in which the Gd was located allowed for rapid water exchange; thus, the resulting material demonstrated large ionic relaxivities (39 s–1 mM–1) in an applied magnetic field of 0.47 T at 40 °C and, as a result of the large loading capacity of the material, also demonstrated high molecular relaxivities (20 000 s–1 mM–1).  相似文献   

12.
Conventional photodynamic therapy (PDT) has limited applications in clinical cancer therapy due to the insufficient O2 supply, inefficient reactive oxygen species (ROS) generation, and low penetration depth of light. In this work, a multifunctional nanoplatform, upconversion nanoparticles (UCNPs)@TiO2@MnO2 core/shell/sheet nanocomposites (UTMs), is designed and constructed to overcome these drawbacks by generating O2 in situ, amplifying the content of singlet oxygen (1O2) and hydroxyl radical (?OH) via water‐splitting, and utilizing 980 nm near‐infrared (NIR) light to increase penetration depth. Once UTMs are accumulated at tumor site, intracellular H2O2 is catalyzed by MnO2 nanosheets to generate O2 for improving oxygen‐dependent PDT. Simultaneously, with the decomposition of MnO2 nanosheets and 980 nm NIR irradiation, UCNPs can efficiently convert NIR to ultraviolet light to activate TiO2 and generate toxic ROS for deep tumor therapy. In addition, UCNPs and decomposed Mn2+ can be used for further upconversion luminescence and magnetic resonance imaging in tumor site. Both in vitro and in vivo experiments demonstrate that this nanoplatform can significantly improve PDT efficiency with tumor imaging capability, which will find great potential in the fight against tumor.  相似文献   

13.
The development of nanomaterials that combine diagnostic and therapeutic functions within a single nanoplatform is extremely important for molecular medicine. Molecular imaging with simultaneous diagnosis and therapy will provide the multimodality needed for accurate diagnosis and targeted therapy. Here, gold‐coated iron oxide (Fe3O4@Au) nanoroses with five distinct functions are demonstrated, integrating aptamer‐based targeting, magnetic resonance imaging (MRI), optical imaging, photothermal therapy. and chemotherapy into one single probe. The inner Fe3O4 core functions as an MRI agent, while the photothermal effect is achieved through near‐infrared absorption by the gold shell, causing a rapid rise in temperature and also resulting in a facilitated release of the anticancer drug doxorubicin carried by the nanoroses. Where the doxorubicin is released, it is monitored by its fluorescence. Aptamers immobilized on the surfaces of the nanoroses enable efficient and selective drug delivery, imaging, and photothermal effect with high specificity. The five‐function‐embedded nanoroses show great advantages in multimodality.  相似文献   

14.
The combination of biocompatible superparamagnetic and photoluminescent nanoparticles (NPs) is intensively studied as highly promising multifunctional (magnetic confinement and targeting, imaging, etc.) tools in biomedical applications. However, most of these hybrid NPs exhibit low signal contrast and shallow tissue penetration for optical imaging due to tissue‐induced optical extinction and autofluorescence, since in many cases, their photoluminescent components emit in the visible spectral range. Yet, the search for multifunctional NPs suitable for high photoluminescence signal‐to‐noise ratio, deep‐tissue imaging is still ongoing. Herein, a biocompatible core/shell/shell sandwich structured Fe3O4@SiO2@NaYF4:Nd3+ nanoplatform possessing excellent superparamagnetic and near‐infrared (excitation) to near‐infrared (emission), i.e., NIR‐to‐NIR photoluminescence properties is developed. They can be rapidly magnetically confined, allowing the NIR photoluminescence signal to be detected through a tissue as thick as 13 mm, accompanied by high T2 relaxivity in magnetic resonance imaging. The fact that both the excitation and emission wavelengths of these NPs are in the optically transparent biological windows, along with excellent photostability, fast magnetic response, significant T2‐contrast enhancement, and negligible cytotoxicity, makes them extremely promising for use in high‐resolution, deep‐tissue dual‐mode (optical and magnetic resonance) in vivo imaging and magnetic‐driven applications.  相似文献   

15.
Thermoresponsive nanocomposites comprising a gold nanoparticle core and a poly(N‐isopropylacrylamide) (pNIPAM) shell are synthesized by grafting the gold nanoparticle surface with polystyrene, which allows the coating of an inorganic core with an organic shell. Through careful control of the experimental conditions, the pNIPAM shell cross‐linking density can be varied, and in turn its porosity and stiffness, as well as shell thickness from a few to a few hundred nanometers is tuned. The characterization of these core–shell systems is carried out by photon‐correlation spectroscopy, transmission electron microscopy, and atomic force microscopy. Additionally, the porous pNIPAM shells are found to modulate the catalytic activity, which is demonstrated through the seeded growth of gold cores, either retaining the initial spherical shape or developing a branched morphology. The nanocomposites also present thermally modulated optical properties because of temperature‐induced local changes of the refractive index surrounding the gold cores.  相似文献   

16.
The multifunctional nanodevice described here integrates nanoscaled imaging, targeting, and controlled drug delivery, as well as the capability to monitor, in situ, the amount of drug released from the nanodevice with single‐cell resolution. The nanodevice is composed of a polymer core/single‐crystal iron oxide shell nanostructure bonded to a quantum dot. It shows outstanding release and retention characteristics via an external on/off manipulation of a high‐frequency magnetic field. Upon magnetic stimulation, the single‐crystal iron oxide shell demonstrates formation of nanometer‐sized polycrystal domains of varying orientation. This allows a variation between retention and slow release of the drug. Further stimulation causes permanent rupturing of the shell, causing release of the drug in a burst‐like manner. The quantum dot bonded to the nanodevice provides optical information for in situ monitoring of the drug release through use of a magnetic field. Remote control drug release from the nanodevice in a cancerous cell line (HeLa) was successfully accomplished using the same induction scenario. When nanodevices equipped with quantum dots are taken into cancerous cells, they are able to provide real‐time drug dose information through a corresponding variation in emission spectrum. The nanodevice designed in this study has achieved its potential as a cell‐based drug‐delivery system for therapeutic applications.  相似文献   

17.
The insufficient blood flow and oxygen supply in solid tumor cause hypoxia, which leads to low sensitivity of tumorous cells and thus causing poor treatment outcome. Here, mesoporous manganese dioxide (mMnO2) with ultrasensitive biodegradability in a tumor microenvironment (TME) is grown on upconversion photodynamic nanoparticles for not only TME‐enhanced bioimaging and drug release, but also for relieving tumor hypoxia, thereby markedly improving photodynamic therapy (PDT). In this nanoplatform, mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO2) with covalently loaded chlorin e6 are obtained as near‐infrared light mediated PDT agents, and then a mMnO2 shell is grown via a facile ultrasonic way. Because of its unique mesoporous structure, the obtained nanoplatform postmodified with polyethylene glycol can load the chemotherapeutic drug of doxorubicin (DOX). When used for antitumor application, the mMnO2 degrades rapidly within the TME, releasing Mn2+ ions, which couple with trimodal (upconversion luminescence, computed tomography (CT), and magnetic resonance imaging) imaging of UCNPs to perform a self‐enhanced imaging. Significantly, the degradation of mMnO2 shell brings an efficient DOX release, and relieve tumor hypoxia by simultaneously inducing decomposition of tumor endogenous H2O2 and reduction of glutathione, thus achieving a highly potent chemo‐photodynamic therapy.  相似文献   

18.
Shell‐crosslinked knedel‐like nanoparticles (SCKs; “knedel” is a Polish term for dumplings) were derivatized with gadolinium chelates and studied as robust magnetic‐resonance‐imaging‐active structures with hydrodynamic diameters of 40 ± 3 nm. SCKs possessing an amphiphilic core–shell morphology were produced from the aqueous assembly of diblock copolymers of poly‐(acrylic acid) (PAA) and poly(methyl acrylate) (PMA), PAA52b–PMA128, and subsequent covalent crosslinking by amidation upon reaction with 2,2′‐(ethylenedioxy)bis(ethylamine) throughout the shell layer. The properties of these materials, including non‐toxicity towards mammalian cells, non‐immunogenicity within mice, and capability for polyvalent targeting, make them ideal candidates for utilization within biological systems. The synthesis of SCKs derivatized with GdIII and designed for potential use as a unique nanometer‐scale contrast agent for MRI applications is described herein. Utilization of an amino‐functionalized diethylenetriaminepentaacetic acid–Gd analogue allowed for direct covalent conjugation throughout the hydrophilic shell layer of the SCKs and served to increase the rotational correlation lifetime of the Gd. In addition, the highly hydrated nature of the shell layer in which the Gd was located allowed for rapid water exchange; thus, the resulting material demonstrated large ionic relaxivities (39 s–1 mM–1) in an applied magnetic field of 0.47 T at 40 °C and, as a result of the large loading capacity of the material, also demonstrated high molecular relaxivities (20 000 s–1 mM–1).  相似文献   

19.
Nanoparticles possess the potential to revolutionize cancer diagnosis and therapy. The ideal theranostic nanoplatform should own long system circulation and active cancer targeting. Additionally, it should be nontoxic and invisible to the immune system. Here, the authors fabricate an all‐in‐one nanoplatform possessed with these properties for personalized cancer theranostics. Platelet‐derived vesicles (PLT‐vesicles) along with their membrane proteins are collected from mice blood and then coated onto Fe3O4 magnetic nanoparticles (MNs). The resulting core–shell PLT‐MNs, which inherit the long circulation and cancer targeting capabilities from the PLT membrane shell and the magnetic and optical absorption properties from the MN core, are finally injected back into the donor mice for enhanced tumor magnetic resonance imaging (MRI) and photothermal therapy (PTT). Meanwhile, it is found that the PTT treatment impels PLT‐MNs targeting to the PTT sites (i.e., tumor sites), and exactly, in turn, the enhanced targeting of PLT‐MNs to tumor sites can improve the PTT effects. In addition, since the PLT membrane coating is obtained from the mice and finally injected into the same mice, PLT‐MNs exhibit stellar immune compatibility. The work presented here provides a new angle on the design of biomimetic nanoparticles for personalized diagnosis and therapy of various diseases.  相似文献   

20.
Yolk‐like nano/microparticles with superparamagnetic iron oxide (SPIO) cores and hierarchical nickel silicate (NS) shells, designated yolk SPIO@NS, are fabricated by combining the versatile sol–gel process and the hydrothermal reaction, involving the coating of SPIO particles with SiO2 and transformation of the SiO2 shells into NS hollow spheres with hierarchical nanostructures. Various yolk/shell nanostructures with tunable NS shell thicknesses and SPIO core sizes are successfully prepared by controlling the experimental para­meters. Au nanoparticles can be impregnated into the yolk‐like microspheres in situ to form SPIO@NS/Au composite particles and the as‐prepared magnetic nanocatalysts show good catalytic activity, using the catalytic reduction of RhB as a model reaction. This facile method can be extended to the synthesis of other encapsulated particles with yolk‐like nanostructure.  相似文献   

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