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1.
Coating gold nanorods (GNRs) with polyelectrolytes is an effective approach to make them biocompatible for potential use in photothermal treatment (PTT) of cancer. The authors report the effect of coating of the GNRs with polystyrene sulphonate (PSS‐GNRs) and PSS plus poly di‐allyl di‐methyl ammonium chloride (PDDAC‐GNRs) on its photothermal conversion efficiency (PTE), cellular uptake and subsequently the photothermal induced cytotoxicity in human oral cancer cells (NT8e). Coating of GNRs with PSS led to decrease in PTE by ∼30% and further coating it with PDDAC led to its increase to similar level, with respect to as‐ prepared GNRs. The cellular uptake of PDDAC‐GNRs in cancer cells was double than that for PSS‐GNRs. PTT of cancer cells after treatment with 60 pM of either PDDAC‐GNRs or PSS‐GNRs resulted in cytotoxicty of ∼90%. At higher concentration of 120 pM, while PSS‐GNRs showed no further change, for PDDAC‐GNR the photothermal induced cytotoxicity decreased to ∼50%. The broadening of longitudinal surface plasmon peak of PDDAC‐GNRs and appearance of dark clusters in cells under bright‐field microscope suggested intracellular clustering of PDDAC‐GNRs. In conclusion, despite high PTE and cellular uptake of PDDAC‐GNRs, its intracellular clustering (due to acidic pH) adversely affect the PTT of cancer cells.Inspec keywords: polymer electrolytes, gold, nanorods, cancer, nanomedicine, cellular biophysics, toxicology, radiation therapy, polymer filmsOther keywords: polyelectrolyte coating, photothermal efficiency, gold nanorods, photothermal induced cancer cell damage, cancer photothermal treatment, polystyrene sulphonate, poly di‐allyl di‐methyl ammonium chloride, photothermal conversion efficiency, cellular uptake, photothermal‐induced cytotoxicity, human oral cancer cells, dark clusters, bright‐field microscope, PDDAC‐GNR intracellular clustering, acidic pH, intracellular compartment, Au  相似文献   

2.
In this work, near-infrared (NIR)-responsive core–shell gold nanorods/mesoporous silica/reduced graphene oxide (Au/SiO2/rGO) nanoparticles with synergistically enhanced photothermal stability and transition effect had been prepared via electrostatic interaction. Gold nanorods (AuNRs) and rGO were employed as the NIR-responsive components. UV–Vis–NIR extinction spectra revealed that the surface plasmon resonance peak of AuNRs from Au/SiO2/rGO nanohybrids remained unchanged after 9 h NIR exposure. UV–Vis–NIR extinction results also showed that thin silica shell was superior to the thick ones in the photothermal stability improvement of Au/SiO2/rGO nanoparticles. Moreover, the doxorubicin release of Au/SiO2/rGO was more rapid than that of Au/SiO2 upon NIR irradiation, indicating that synergistically enhanced photothermal effect between rGO and AuNRs endowed Au/SiO2/rGO nanoparticles with excellent photothermal transition efficiency. Such novel NIR-responsive core–shell hybrid nanoparticles with enhanced photothermal stability and transition effect are well suited for further biological applications, such as photothermal therapy, bioimaging and drug delivery.  相似文献   

3.
Gold nanorods (GNRs) with exceptional photothermal properties have held promising potential for application in the biomedical field. In this study, the authors achieved photothermal ablation by polyethylene glycol (PEG)‐functionalised GNRs. Well‐dispersed and uniform GNRs were produced through a seed‐mediated growth method. A thermal camera was used to scrutinise the temperature distribution and efficiency of the photothermal properties of the GNRs, which were irradiated by an 808 nm laser on a silicon chip. They observed that the GNRs provided about a 5°C temperature increase and produced hyperthermia efficiently. Since GNRs need to be surface tailored with a biocompatible material rather than cetyltrimethylammonium bromide (CTAB), they chose methoxyl PEG thiol to modify the GNRs. By taking advantage of the alkaline environment that assists this functionalisation, they accomplished about 89% removal of CTAB and identified a PEG layer on the surface of the GNRs. The GNR biocompatibility was considerably improved without any shift of the optical properties. Hepatocellular carcinoma cells were incubated with GNRs for 24 h and then were irradiated with a near‐infrared laser for 3 min. Few cells remained alive, which demonstrated the photothermal ablation ability of the GNRs.Inspec keywords: cancer, nanofabrication, biomedical materials, nanorods, gold, nanoparticles, nanomedicine, cellular biophysics, hyperthermia, photothermal effects, photodynamic therapy, laser applications in medicine, infrared imaging, biomedical optical imaging, filled polymersOther keywords: highly efficient polyethylene glycol‐functionalised gold nanorods, hepatocellular carcinoma cells, temperature distribution, photothermal ablation ability, well‐dispersed gold nanorods, seed‐mediated growth method, thermal camera, laser on a silicon chip, near‐infrared laser, wavelength 808.0 nm, time 24.0 hour, time 3.0 min, temperature 5.0 degC, Au  相似文献   

4.
In this work, gold nanorods (AuNRs)/mesoporous silica (SiO2) nanoparticles capped with thermal-responsive polymer were fabricated to couple the photothermal property of AuNRs and the thermal-/pH-responsive properties of polymer in a single nanovehicle. Aliphatic poly(urethane-amine) (PUA) was employed as the smart polymer to cap the mesopores of AuNRs/SiO2 nanoparticles via in situ polymerization in supercritical CO2. Thermal-/pH-responsive PUA acted as the on–off switch to control the DOX release due to the stretch and shrinkage of the PUA polymer chains at different temperatures, whereas a remote near-infrared (NIR) light was used to activate the phase change and subsequent drug release. The in vitro drug release studies indicated that Au/SiO2/PUA nanoparticles exhibited distinguished pH-, thermal-, and NIR-dependent release properties. A short time exposure to NIR irradiation could distinctly increase the local temperature of nanoparticles, and the thermal-responsive polymeric cap enabled the DOX release in a significant reversible way by simply adjusting the NIR laser intensity. The present paper provides an ideal way to fabricate NIR-responsive drug carriers by combining stimuli-responsive polymer with inorganic matrix, which is highly attractive for remote controllable drug delivery.  相似文献   

5.
Cancer nanotheranostics, integrating both diagnostic and therapeutic functions into nanoscale agents, are advanced solutions for cancer management. Herein, a light‐responsive biodegradable nanorattle‐based perfluoropentane‐(PFP)‐filled mesoporous‐silica‐film‐coated gold nanorod (GNR@SiO2‐PFP) is strategically designed and prepared for enhanced ultrasound (US)/photoacoustic (PA) dual‐modality imaging guided photothermal therapy of melanoma. The as‐prepared nanorattles are composed of a thin mesoporous silica film as the shell, which endows the nanoplatform with flexible morphology and excellent biodegradability, as well as large cavity for PFP filling. Upon 808 nm laser irradiation, the loaded PFP will undergo a liquid–gas phase transition due to the heat generation from GNRs, thus generating nanobubbles followed by the coalescence into microbubbles. The conversion of nanobubbles to microbubbles can improve the intratumoral permeation and retention in nonmicrovascular tissue, as well as enhance the tumor‐targeted US imaging signals. This nanotheranostic platform exhibits excellent biocompatibility and biodegradability, distinct gas bubbling phenomenon, good US/PA imaging contrast, and remarkable photothermal efficiency. The results demonstrate that the GNR@SiO2‐PFP nanorattles hold great potential for cancer nanotheranostics.  相似文献   

6.
The photothermal properties of gold nanorods (GNRs) provide an opportunity for the clinical application of highly efficient and tumor-specific photothermal therapy. For the effective hyperthermic ablation of tumor tissue using GNRs, it is essential to maintain a homogeneous therapeutic temperature in the target tissue during treatment. This study investigates whether the concentration of GNRs affects the distribution of the temperature increase during hyperthermal therapy. The investigation is conducted using polyacrylamide phantoms containing varying amounts of GNRs. In 0.1, 0.25, and 0.5 nM GNR-suspended phantoms, the change in temperature is relatively uniform along the depth of each phantom during laser irradiation at 2 W cm(-2) . In 1.0, 2.0, and 5.0 nM GNR-suspended phantoms, the rates of temperature increase in the deep regions of the phantoms decrease with increasing GNR concentration. At a laser irradiation of 5 W cm(-2) , the temperature of the GNR-suspended phantoms increases at a faster rate, whereas the range of GNR concentrations for maintaining the homogeneity of the temperature increase is not affected. This suggests that the concentration of GNRs is the major determinant of the depth-related temperature increase during hyperthermic ablation. Therefore, prior to the clinical application of hyperthermic ablation using GNRs, the concentration of GNRs has to be optimized to ensure a homogeneous distribution of therapeutic temperature in the targeted tissue.  相似文献   

7.
Graphene oxide/gold nanorod (GO/GNR) nanohybrids were synthesized with a GO- and gold-seed-mediated in situ growth method at room temperature by mixing polystyrene sulfonate (PSS) functionalized GO, secondary growth solution, and gold seeds. Compared with ex situ preparation methods of GO/GNRs or graphene (G)/GNRs, the in situ synthesis of GO/GNRs addressed the issue of the aggregation of the GNRs before their attachment onto the GO. The method is straightforward and environment-friendly. The GO/GNRs showed a remarkable photothermal effect in vitro. The temperature of the GO/GNR nanohybrids increased from 25 to 49.9 °C at a concentration of 50 μg/mL after irradiation with an 808-nm laser (0.4 W/cm2) for 6 min. Additionally, the GO/GNRs exhibited good optical and morphological stability and photothermal properties after six cycles of laser irradiation. Upon injection of the GO/GNRs into xenograft tumors, excellent computed tomography (CT) imaging properties and photothermal effect were obtained. The preclinical CT agent iohexol was combined with the GO/GNRs and further enhanced CT imaging. Therefore, the GO/GNR nanohybrids have great potential for precise CT-image-guided tumor photothermal treatment.
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8.
A self‐assembled DNA origami (DO)‐gold nanorod (GNR) complex, which is a dual‐functional nanotheranostics constructed by decorating GNRs onto the surface of DNA origami, is demonstrated. After 24 h incubation of two structured DO‐GNR complexes with human MCF7 breast cancer cells, significant enhancement of cell uptake is achieved compared to bare GNRs by two‐photon luminescence imaging. Particularly, the triangle shaped DO‐GNR complex exhibits optimal cellular accumulation. Compared to GNRs, improved photothermolysis against tumor cells is accomplished for the triangle DO‐GNR complex by two‐photon laser or NIR laser irradiation. Moreover, the DO‐GNR complex exhibits enhanced antitumor efficacy compared with bare GNRs in nude mice bearing breast tumor xenografts. The results demonstrate that the DO‐GNR complex can achieve optimal two‐photon cell imaging and photothermal effect, suggesting a promising candidate for cancer diagnosis and therapy both in vitro and in vivo.  相似文献   

9.
Bacillus subtilis spores (a simulant of Bacillus anthracis) have been imaged by two-photon luminescence (TPL) microscopy, using gold nanorods (GNRs) functionalized with a cysteine-terminated homing peptide. Control experiments using a peptide with a scrambled amino acid sequence confirmed that the GNR targeting was highly selective for the spore surfaces. The high sensitivity of TPL combined with the high affinity of the peptide labels enables spores to be detected with high fidelity using GNRs at femtomolar concentrations. It was also determined that GNRs are capable of significant TPL output even when irradiated at near infrared (NIR) wavelengths far from their longitudinal plasmon resonance (LPR), permitting considerable flexibility in the choice of GNR aspect ratio or excitation wavelength for TPL imaging.   相似文献   

10.
It is of great importance in drug delivery to fabricate multifunctional nanocarriers with intelligent targeting properties, for cancer diagnosis and therapy. Herein, hollow‐structured CuS@Cu2S@Au nanoshell/satellite nanoparticles are designed and synthesized for enhanced photothermal therapy and photoswitchable targeting theranostics. The remarkably improved photothermal conversion efficiency of CuS@Cu2S@Au under 808 nm near‐infrared (NIR) laser irradiation can be explained by the reduced bandgap and more circuit paths for electron transitions for CuS and Cu2S modified with Au nanoparticles, as calculated by the Vienna ab initio simulation package, based on density functional theory. By modification of thermal‐isomerization RGD targeting molecules and thermally sensitive copolymer on the surface of nanoparticles, the transition of the shielded/unshielded mode of RGD (Arg‐Gly‐Asp) targeting molecules and shrinking of the thermally sensitive polymer by NIR photoactivation can realize a photoswitchable targeting effect. After loading an anticancer drug doxorubicin in the cavity of CuS@Cu2S@Au, the antitumor therapy efficacy is greatly enhanced by combining chemo‐ and photothermal therapy. The reported nanohybrid can also act as a photoacoustic imaging agent and an NIR thermal imaging agent for real‐time imaging, which provides a versatile platform for multifunctional theranostics and stimuli‐responsive targeted cancer therapy.  相似文献   

11.
The nanoplatform GNR‐ACPP‐PpIX (designated as GNR‐ACPI) is designed for dual image guided combined activatable photodynamic therapy (PDT) and photothermal therapy (PTT). In GNR‐ACPI, gold nanorods (GNRs) are modified with a protoporphyrin (PpIX, a PDT agent) conjugated activatable cell penetrating peptide (ACPP), which consists of the matrix metalloproteinases‐2 (MMP‐2) sensitive peptide sequence GPLGLAG. First, the photoactivity of PpIX is effectively quenched by GNRs due to the strong near infrared region light absorption of GNR and the special “U type” structure of ACPP induced close contact between PpIX and GNR. However, once arriving at the tumor site, the GPLGLAG sequence is hydrolyzed by the MMP‐2 overexpressed by tumor cells, resulting in the release of the residual cell membrane penetrating peptide (CPP) attached PpIX (CPP‐PpIX) with the recovery of photoactivity of PpIX. In addition, with the help of CPP, more efficient cellular uptake of PpIX by tumor cells can be achieved, which will greatly improve the PDT efficacy. Moreover, the GNR can also be utilized for photothermic imaging as well as PTT for tumors. It is found that the combination of PTT and PDT under the guidance of dual‐mode imaging greatly enhances the antitumor effects, while possessing negligible systematic toxicity.  相似文献   

12.
Light‐triggered drug delivery based on near‐infrared (NIR)‐mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light‐responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light‐absorber, Rb x WO3 (rubidium tungsten bronze, Rb‐TB) nanorods. With doxorubicin (DOX) payload, the DOX‐loaded Rb‐TB composite (Rb‐TB‐DOX) simultaneously provides a burst‐like drug release and intense heating effect upon 808‐nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb‐TB‐DOX to the MCF‐7 cancer cells. Most remarkably, Rb‐TB‐DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX‐resistant MCF‐7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo‐photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo‐photothermal therapy is also conducted and realized on pancreatic (Pance‐1) tumor‐bearing nude mice. Apart from its promise for cancer therapy, the as‐prepared Rb‐TB can also be employed as a new dual‐modal contrast agent for photoacoustic tomography and (PAT) X‐ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X‐ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb x WO3 nanorods for applications in cancer theranostics.  相似文献   

13.
Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 μg.ml−1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic‐diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti‐cancer drug doxorubicin.  相似文献   

14.
Multifunctional nanoparticles possessing magnetization and near‐infrared (NIR) absorption have warranted interest due to their significant applications in magnetic resonance imaging, diagnosis, bioseparation, target delivery, and NIR photothermal ablation. Herein, the site‐selective assembly of magnetic nanoparticles onto the ends or ends and sides of gold nanorods with different aspect ratios (ARs) to create multifunctional nanorods decorated with varying numbers of magnetic particles is described for the first time. The resulting hybrid nanoparticles are designated as Fe3O4? Aurod? Fe3O4 nanodumbbells and Fe3O4? Aurod necklacelike constructs with tunable optical and magnetic properties, respectively. These hybrid nanomaterials can be used for multiplex detection and separation because of their tunable magnetic and plasmonic functionality. More specifically, Fe3O4? Aurod necklacelike probes of different ARs are utilized for simultaneous optical detection based on their plasmon properties, magnetic separation, and photokilling of multiple pathogens from a single sample at one time. The combined functionalities of the synthesized probes will open up many exciting opportunities in dual imaging for targeted delivery and photothermal therapy.  相似文献   

15.
Preparation of manganese ferrite (MnFe2 O4) nanorods by the reduction of akaganeite seeds in the presence of oleylamine is reported. The Mn‐doped β‐FeOOH akaganeite seeds have been processed by the hydrolysis of metal‐chloride salts in the presence of polyethylenimine (PEI) surfactant. The hydrophobic oleylamine capped nanorods are made hydrophilic using trisodium citrate as a phase transferring agent. The nanorods form with an aspect ratio of 5.47 and possess a high magnetisation value of 69 emu/g at an applied magnetic field of 1.5 T. The colloidal water dispersion of nanorods exhibits superior heating efficiency by the application of alternating magnetic field (AMF). A specific absorption rate value of 798 W/g is achieved at an applied AMF of field strength 500 Oe and frequency 316 kHz. Further, the citrate functionalised nanorods are capable of attaching with doxorubicin (DOX) electrostatically with a loading efficiency of 97% and the drug release is pH responsive. The DOX loaded nanorods show a promising effect on the apoptosis of MCF‐7 as experimented in vitro.Inspec keywords: manganese, hydrophobicity, drug delivery systems, cellular biophysics, magnetic particles, ferrites, manganese compounds, colloids, hyperthermia, pH, iron compounds, biomedical materials, cancer, nanofabrication, nanomagnetics, hydrophilicity, nanoparticles, magnetisation, nanorods, nanomedicineOther keywords: enhanced drug delivery, hyperthermia application, manganese ferrite nanorods, polyethylenimine surfactant, hydrophilic using trisodium citrate, phase transferring agent, high magnetisation, applied magnetic field, heating efficiency, absorption rate, hydrophobic oleylamine capped nanorods, reduction, akaganeite seeds, hydrolysis, trisodium citrate, hydrophilicity, colloidal water dispersion, alternating magnetic field, frequency 316.0 kHz, FeOOH:Mg, MnFe2 O4   相似文献   

16.
Jung Y  Reif R  Zeng Y  Wang RK 《Nano letters》2011,11(7):2938-2943
In this paper, we demonstrate an application of a noninvasive imaging modality, photothermal optical coherence tomography (PT-OCT), for imaging gold nanorods (GNRs) uptake in sentinel lymph node (SLN) of mice in situ. This application enables us to obtain higher quality images of SLN structures due to the photothermal contrast properties of the GNRs. It is also demonstrated that GNRs accumulate differently within several SLN structures, and this uptake is time dependent. Finally, we determine the average concentration of GNRs within the whole SLN which is used to demonstrate uptake kinetics of the nanoparticles.  相似文献   

17.
Converting solar energy into chemical fuels is increasingly receiving a great deal of attention. In this work, CdS nanoparticles (NPs) are solvothermally anchored onto graphene nanoribbons (GNRs) that are longitudinally unzipped from multiwalled carbon nanotubes. The as‐synthesized CdS/GNR nanocomposites with recyclability present GNR content‐dependent activity in visible‐light‐driven hydrogen evolution from water splitting. In a range of 1–10 wt% GNRs, the CdS/GNR composites with 2 wt% GNRs achieves the greatest hydrogen evolution rate of 1.89 mmol h?1 g?1. The corresponding apparent quantum efficiency is 19.3%, which is ≈3.7 times higher than that of pristine CdS NPs. To elucidate the underlying photocatalytic mechanism, a systematic characterization, including in situ irradiated X‐ray photoelectron spectroscopy and Kelvin probe measurements, is performed. In particular, the interfacial charge transfer pathway and process from CdS NPs to GNRs is revealed. This work may open avenues to fabricate GNR‐based nanocomposites for solar‐to‐chemical energy conversion and beyond.  相似文献   

18.
Multimodal imaging guided synergistic therapy promises more accurate diagnosis than any single imaging modality, and higher therapeutic efficiency than any single one or their simple “mechanical” combination. Herein, we report a dual‐stimuli responsive nanotheranostic based on a hierarchical nanoplatform, composed of mesoporous silica‐coated gold nanorods (GNR@SiO2), Indocyanine Green (ICG), and 5‐fluorouracil (5‐FU), for in vivo multimodal imaging guided synergistic therapy. The 5‐FU loaded ICG‐conjugated silica‐coated gold nanorods (GNR@SiO2‐5‐FU‐ICG) was able to response specifically to the two stimuli of pH change and near‐infrared (NIR) light irradiation. Both the NIR light irradiation and acidic environment accelerated the 5‐FU release. Meanwhile, the heat generation and singlet oxygen production can be induced by GNR@SiO2‐5‐FU‐ICG upon light irradiation. Most intriguingly, the nanoplatform also promises multimodal imaging such as two‐photon luminescence, fluorescence, photoacoustic, photothermal imaging, as well as trimodal synergistic therapy such as photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy. The cancer theranostic capability of GNR@SiO2‐5‐FU‐ICG was evaluated both in vitro and in vivo. The trimodal synergistic therapy with the guidance of multimodal imaging exhibited remarkably enhanced treatment efficacy. This concept of a hierarchical nanoplatform integrates multiple diagnostic/therapeutic modalities into one platform, which can potentially be applied as personalized nanomedicine with drug delivery, diagnosis, and treatment.  相似文献   

19.
A versatile system combining chemotherapy with photothermal therapy for cancer cells using Pd nanosheet‐covered hollow mesoporous silica nanoparticles is reported. While the hollow mesoporous silica core can be used to load anticancer drugs (i.e., doxorubicin) for chemotherapy, the Pd nanosheets on the surface of particles can convert NIR light into heat for photothermal therapy. More importantly, the loading of Pd nanosheets on hollow mesoporous silica nanospheres can dramatically increase the amount of cellular internalization of the Pd nanosheets: almost 11 times higher than the unloaded Pd nanosheets. The as‐prepared nanocomposites efficiently deliver both drugs and heat to cancer cells to improve the therapeutic efficiency with minimal side effects. Compared with chemotherapy or photothermal therapy alone, the combination of chemotherapy and phototherapy can significantly improve the therapeutic efficacy, exhibiting a synergistic effect.  相似文献   

20.
Advanced biocompatible and robust platforms equipped with diverse properties are highly required in biomedical imaging applications for the early detection of atherosclerotic vascular disease and cancers. Designing nanohybrids composed of noble metals and fluorescent materials is a new way to perform multimodal imaging to overcome the limitations of single-modality counterparts. Herein, we propose the novel design of a multimodal contrast agent; namely, an enhanced nanohybrid comprising gold nanorods (GNRs) and carbon dots (CDs) with silica (SiO2) as a bridge. The nanohybrid (GNR@SiO2@CD) construction is based on covalent bonding between SiO2 and the silane-functionalized CDs, which links the GNRs with the CDs to form typical core–shell units. The novel structure not only retains and even highly improves the optical properties of the GNRs and CDs, but also possesses superior imaging performance in both diffusion reflection (DR) and fluorescence lifetime imaging microscopy (FLIM) measurements compared with bare GNRs or fluorescence dyes and CDs. The superior bioimaging properties of the GNR@SiO2@CD nanohybrids were successfully exploited for in vitro DR and FLIM measurements of macrophages within tissue-like phantoms, paving the way toward a theranostic contrast agent for atherosclerosis and cancer.
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