Zhen Guo

Multifunctional Fe3O4@C@Ag hybrid nanoparticles as dual modal imaging probes and near-infrared light-responsive drug delivery platform.

Multifunctional nanocarriers based on Fe(3)O(4)@C@Ag hybrid nanoparticles with a diameter of 200 nm were fabricated by a facile method. Silver (Ag) nanoparticles were deposited onto the surface of Fe(3)O(4)@C nanospheres in dimethyl formamide (DMF) solution by reducing silver nitrate (AgNO(3)) with glucose. The nanocarriers of doxorubicin (DOX) with a high loading content of 997 mg/g and near-infrared (NIR) light-responsive drug delivery based on Ag nanoparticles were realized. Strong fluorescence can be observed in cell nucleus due to the presence of DOX after irradiated by NIR, and most cells were in the state of apoptosis, which indicates NIR-regulated drug release was realized. Moreover, measurements show that the nanocarriers could also be used as magnetic resonance imaging (MRI) contrast agents and fluorescent probes. The combination of synergistic NIR controlled drug release and dual modal imaging of MRI and two-photon fluorescence (TPF) imaging could lead to a potential multifunctional system for biomedical diagnosis and therapy.

Novel Mn3 [Co(CN)6]2@SiO2@Ag Core-Shell Nanocube: Enhanced Two-Photon Fluorescence and Magnetic Resonance Dual-Modal Imaging-Guided Photothermal and Chemo-therapy.

The versatile Mn3[Co(CN)6]2@SiO2@Ag core-shell NCs are prepared by a simple coprecipitation method. Ag nanoparticles with an average diameter of 12 nm deposited on the surface of Mn3[Co(CN)6]2@SiO2 through S-Ag bonding are fabricated in ethanol solution by reducing silver nitrate (AgNO3 ) with NaBH4 . The NCs possess T1 -T2 dual-modal magnetic resonance imaging ability. The inner Prussian blue analogs (PBAs) Mn3[Co(CN)6]2 exhibit bright two-photon fluorescence (TPF) imaging when excited at 730 nm. Moreover, the TPF imaging intensity displays 1.85-fold enhancement after loading of Ag nanoparticles. Besides, the sample also has multicolor fluorescence imaging ability under 403, 488, and 543 nm single photon excitation. The as-synthesized Mn3[Co(CN)6]2@SiO2@Ag NCs show a DOX loading capacity of 600 mg g(-1) and exhibit an excellent ability of near-infrared (NIR)-responsive drug release and photothermal therapy (PTT) which is induced from the relative high absorbance in NIR region. The combined chemotherapy and PTT against cancer cells in vitro test shows high therapeutic efficiency. The multimodal treatment and imaging could lead to this material a potential multifunctional system for biomedical diagnosis and therapy.

Mn3[Co(CN)6]2@SiO2 Core-shell Nanocubes: Novel bimodal contrast agents for MRI and optical imaging

Nanoprobes with dual modal imaging of magnetic resonance imaging (MRI) and two-photon fluorescence (TPF) can serve as promising platforms for clinical diagnosis. A wide range of molecules and nanoparticles have been investigated as agents for contrast enhanced MRI and fluorescence imaging in cancer diagnosis. However, a single material with dual modal imaging of MRI and TPF is rarely reported. We found that Mn3[Co(CN)6]2 nanocubes can serve as agents for both T1- and T2-weighted MRI, and TPF imaging. The nanocubes coated with silica to form Mn3[Co(CN)6]2@SiO2 core-shell nanocubes were readily internalized by cells without showing cytotoxicity. In vitro tests, the core-shell nanocubes display relatively high longitudinal (r1) and transverse (r2) relaxivities, they also manifest a remarkable T1 and T2 contrast effects at in-vivo imaging of internal organs in Mice. Moreover, the core-shell nanocubes could offer high-resolution cell fluorescence imaging by two-photon excitation (720 nm) or by conventional fluorescence with 403- or 488-nm excitation.

Fe3O4@carbon@zeolitic imidazolate framework-8 nanoparticles as multifunctional pH-responsive drug delivery vehicles for tumor therapy in vivo

Controlled drug release is a promising approach for cancer therapy due to its merits of reduced systemic toxicity and enhanced antitumor efficacy. Here, multifunctional Fe3O4@carbon@zeolitic imidazolate framework-8 (FCZ) hybrid nanoparticles (NPs) were successfully constructed. Owing to the porosity and acid-sensitivity of zeolitic imidazolate framework-8 (ZIF-8), FCZ NPs not only displayed an improved drug loading capacity compared to most of the polymeric nanocarriers, but also exhibited excellent pH-triggered release of doxorubicin (DOX) in vitro. Moreover, carbon dots (CDs) embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals could simultaneously function as intracellular fluorescence imaging and T2*-weighted magnetic resonance imaging (MRI) contrast agents, respectively. The results obtained from the MTT assay demonstrated good biocompatibility of FCZ NPs. DOX release experiments showed pH regulation-dominated drug release kinetics: a weak acidic pH in tumor areas could trigger sustained drug release, suggesting that FCZ NPs are ideal drug delivery systems. Moreover, the remarkable inhibition of tumor growth without side effects was confirmed in vivo. These results provide convincing evidence establishing the multifunctional FCZ NPs as promising candidates for tumor therapy.

Multifunctional mesoporous nanoparticles as pH-responsive Fe2+ reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth

Artemisinin (ART) is an iron-dependent anti-cancer drug. However, simultaneous delivery of hydrophobic ART and Fe(2+) ions into cancer cells remains a major challenge. Herein, we reported Fe3O4@C/Ag@mSiO2 (FCA@mSiO2) multifunctional nanocarriers which can load ART as high as 484 mg/g. Moreover, FCA@mSiO2 nanoparticles demonstrated pH-responsive Fe(2+) release, the concentration of Fe(2+) ions can reach 2.765 nmol/L in HeLa cells cultured with FCA@mSiO2 nanoparticles. The antitumor efficacy of ART-loaded FCA@mSiO2 nanoparticles measured by MTT assay was significantly enhanced compared with free ART. It was suggested that the ART-loaded FCA@mSiO2 nanoparticles are internalized by HeLa cells and located at the acidic compartments of endosomes and lysosomes, releasing Fe(2+) ions to non-enzymatically convert ART to toxic products for killing cancer cells. This result provides a way for using promising natural drugs in anti-cancer therapeutics.

pH-Responsive Iron Manganese Silicate Nanoparticles as T1-T2* Dual-Modal Imaging Probes for Tumor Diagnosis

Magnetic resonance imaging (MRI) probes can be concentrated in tumors through grafting targeting agents. However, the clinical application of such targeted MRI probes is largely limited because specific agents are only used to target specific characteristics of cancer cells. The development of the MRI probes that can be used regardless of tumor types or their developmental stages is highly appreciated. The acidic tumor microenvironments and acidic organelles (endosomes/lysosomes) in cancer cells are universal phenomena of solid tumors, and nanoparticles can also accumulate in tumor tissues by enhanced permeability and retention (EPR) effect. Here, we reported the synthesis of pH-responsive T1-T2* dual-modal contrast agents based on iron manganese silicate (FeMn(SiO4)) hollow nanospheres, which can release Mn(2+) ions in acidic environments, exhibiting excellent ability as agents for magnetic resonance and red fluorescence imaging. MRI for mouse models revealed that the nanoprobes could accumulate in tumors via EPR effect and then distinguish tumors from normal tissues with the synergistic effect of T1 and T2* signal only 10 min after intravenous injection. Fluorescence imaging demonstrated that the nanoprobes could be endocytosed into cancer cells and located at their lower pH compartments. Moreover, the hollow nanospheres showed no obvious toxicity and inflammation to the major organs of mice, which made them attractive diagnostic agents for different types of cancers.

Preparation and biological characterization of hollow magnetic Fe3O4@C nanoparticles as drug carriers with high drug loading capability, pH-control drug release and MRI properties

Fe3O4@C nanocapsules were synthesized via a sacrificial-template method by coating SiO2 nanospheres with an Fe3O4@C double-shell structure, followed by dissolving SiO2 nanospheres through ammonia water under hydrothermal conditions. The nanocapsules show a loading capacity as high as 1300 mg g-1 for doxorubicin (DOX), and the DOX loaded on the surface of the carbon shells displays pH-sensitive release behavior. Drug release experiments were carried out at pH 7.4, 6.2 and 5.0. It was found that the drug release rate at pH 6.2 was about two times as fast as that at pH 7.4, and even faster at pH 5.0. A MTT assay was used to test the cytotoxicity of the DOX, nanocapsules and DOX-nanocapsules, which indicated the low cytotoxicity of the nanocapsules towards cells. The DOX-nanocapsules can be taken up by cancer cells through endocytosis, releasing DOX into the cytoplasm, which was observed by both transmission electron microscopy and confocal microscopy. In vitro magnetic resonance imaging (MRI) experiments validated the potential use of these nanocapsules as MRI contrast agents.

Biodegradable Core-shell Dual-Metal-Organic-Frameworks Nanotheranostic Agent for Multiple Imaging Guided Combination Cancer Therapy

Metal-organic-frameworks (MOFs) possess high porosity, large surface area, and tunable functionality are promising candidates for synchronous diagnosis and therapy in cancer treatment. Although large number of MOFs has been discovered, conventional MOF-based nanoplatforms are mainly limited to the sole MOF source with sole functionality. In this study, surfactant modified Prussian blue (PB) core coated by compact ZIF-8 shell (core-shell dual-MOFs, CSD-MOFs) has been reported through a versatile stepwise approach. With Prussian blue as core, CSD-MOFs are able to serve as both magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) agents. We show that CSD-MOFs crystals loading the anticancer drug doxorubicin (DOX) are efficient pH and near-infrared (NIR) dual-stimuli responsive drug delivery vehicles. After the degradation of ZIF-8, simultaneous NIR irradiation to the inner PB MOFs continuously generate heat that kill cancer cells. Their efficacy on HeLa cancer cell lines is higher compared with the respective single treatment modality, achieving synergistic chemo-thermal therapy efficacy. In vivo results indicate that the anti-tumor efficacy of CSD-MOFs@DOX+NIR was 7.16 and 5.07 times enhanced compared to single chemo-therapy and single thermal-therapy respectively. Our strategy opens new possibilities to construct multifunctional theranostic systems through integration of two different MOFs.

Novel Metal Polyphenol Framework for MR Imaging-Guided Photothermal Therapy

Phothermal therapy has received increasing attention in recent years as a potentially effective way to treat cancer. In pursuit of a more biocompatible photothermal agent, we utilize biosafe materials including ellagic acid (EA), polyvinylpyrrolidone (PVP), and iron element as building blocks, and we successfully fabricate a homogeneous nanosized Fe-EA framework for the first time by a facile method. As expected, the novel nanoagent exhibits no obvious cytotoxicity and good hemocompatibility in vitro and in vivo. The microenvironment responsiveness to both pH and hydrogen peroxide makes the NPs biodegradable in tumor tissues, and the framework should be easily cleared by the body. Photothermal potentials of the nanoparticles are demonstrated with relevant features of strong NIR light absorption, moderately effective photothermal conversion efficiency, and good photothermal stability. The in vivo photothermal therapy also achieved effective tumor ablation with no apparent toxicity. On the other hand, it also exhibits T2 MR imaging ability originated from ferric ions. Our work highlights the promise of the Fe-EA framework for imaging-guided photothermal therapy.

Photo-Enhanced Singlet Oxygen Generation of Prussian Blue-based Nanocatalyst for Imaging-Guided Augmented Photodynamic Therapy

Summary Therapeutic effects of photodynamic therapy (PDT) remain largely limited because of tumor hypoxia. Herein, we report safe and versatile nanocatalysts (NCs) for endogenous oxygen generation and imaging-guided enhanced PDT. The NCs (named as PSP) are prepared by coating Prussian blue (PB) with mesoporous silica to load photosensitizer (zinc phthalocyanine, ZnPc), followed by the modification of polyethylene glycol chains. The inner PB not only acts like a catalase for hydrogen peroxide decomposition but also serves as a photothermal agent to increase the local temperature and then speed up the oxygen supply under near-infrared irradiation. The loaded ZnPc can immediately transform the formed oxygen to generate cytotoxic singlet oxygen upon the same laser irradiation due to the overlapped absorption between PB and ZnPc. Results indicate that the PSP-ZnPc (PSPZP) NCs could realize the photothermally controlled improvement of hypoxic condition in cancer cells and tumor tissues, therefore demonstrating enhanced cancer therapy by the incorporation of PDT and photothermal therapy.