Huimao Zhang

Conjugation of NaGdF4 upconverting nanoparticles on silica nanospheres as contrast agents for multi-modality imaging

Here, we report the covalently conjugation of lanthanide doped NaGdF4:Yb(3+), Er(3+)@NaGdF4 upconverting nanoparticles (UCNPs) on methylphosphonate functionalized silica nanospheres (pSi NPs) for in vivo upconversion luminescence (UCL), T1-weighted magnetic resonance (MR), and X-ray computed tomography (CT) multi-modality imaging. The nanocomposites (pSi@UCNPs) were synthesized by a facile ligand exchange strategy. The hydrophobic pSi@UCNPs were transferred into aqueous solution by surface coating Pluronic F127. The Pluronic F127 coated pSi@UCNPs (pSi@UCNPs@F127) exhibit excellent stability in biological medium, inappreciable cytotoxicity and negligible organ toxicity. The pSi@UCNPs@F127 also shows brighter UCL, and higher CT/MR enhancements than that of Pluronic F127 coated NaGdF4:Yb(3+), Er(3+)@NaGdF4 UCNP. In detail, the capability of pSi@UCNPs@F127 as high performance contrast agents for in vivo multi-modality (UCL/MR/CT) imaging is evaluated successfully through small-animal experiments.

Facile Preparation of Doxorubicin-Loaded Upconversion@Polydopamine Nanoplatforms for Simultaneous In Vivo Multimodality Imaging and Chemophotothermal Synergistic Therapy

The development of biosafe nanoplatforms with diagnostic and therapeutic multifunction is extremely demanded for designing cancer theranostic medicines. Here, a facile methodology is developed to construct a multifunctional nanotheranostic that gathers five functions, upconversion luminescence (UCL) imaging, T1-weighted magnetic resonance imaging (MRI), X-ray computed tomography (CT) imaging, photothermal therapy (PTT), and chemotherapy, into one single nanoprobe (named as UCNP@PDA5-PEG-DOX). For generating the UCNP@PDA5-PEG-DOX, a near-infrared light (NIR)-absorbing polydopamine (PDA) shell is directly coated on oleic-acid-capped β-NaGdF4:Yb(3+),Er(3+)@β-NaGdF4 upconverting nanoparticle (UCNP) core for the first time to form monodisperse, ultrastable, and noncytotoxic core-shell-structured nanosphere via water-in-oil microemulsion approach. When combined with 808 nm NIR laser irradiation, the UCNP@PDA5-PEG-DOX shows great synergistic interaction between PTT and the enhanced chemotherapy, resulting in completely eradicated mouse-bearing SW620 tumor without regrowth. In addition, leakage study, hemolysis assay, histology analysis, and blood biochemistry assay unambiguously reveal that the UCNP@PDA5-PEG has inappreciable cytotoxicity and negligible organ toxicity. The results provide explicit strategy for fabricating multifunctional nanoplatforms from the integration of UCNP with NIR-absorbing polymers, important for developing multi-mode nanoprobes for biomedical applications.

Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications

An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.

Controllable synthesis of polydopamine nanoparticles in microemulsions with pH-activatable properties for cancer detection and treatment

Polydopamine nanoparticles (PDA NPs) which combine diagnostic and therapeutic functions are potentially useful in biomedicine. However, it is difficult to synthesize PDA NPs of a relatively small size (≤50 nm in diameter) using the traditional polymerization of dopamine monomers in an alkaline water-ethanol solution at room temperature. Herein, PDA NPs with average diameters ranging from 25 nm to 43 nm are prepared in a way which is similar to the silica-like reverse microemulsion process. The size of the PDA NPs can be modulated by changing the amount of dopamine monomers in the microemulsion. After conjugation with ferric ions (Fe3+), the poly(ethylene glycol) modified Fe-PDA NPs (termed as PEG-Fe-PDA NPs) exhibited pH-activatable magnetic resonance imaging (MRI) contrast and high photothermal performance. The combination of a small dimension and the pH-activatable MRI contrast can greatly facilitate tumor accumulation and increase the tumor imaging sensitivity against animal models in vivo. Completely inhibited tumor growth was achieved by the PEG-Fe-PDA NPs mediated by photothermal therapy with MRI guidance.

Lectin-conjugated Fe2O3@Au core@Shell nanoparticles as dual mode contrast agents for in vivo detection of tumor.

Here, we report the covalent conjugation of lectin on Fe2O3@Au core@shell nanoparticle (lectin-Fe2O3@Au NP) for T2-weighted magnetic resonance (MR) and X-ray computed tomography (CT) dual-modality imaging. The lectin-Fe2O3@Au NPs are prepared by coupling lectins to the Fe2O3@Au NP surfaces through bifunctional PEG NHS ester disulfide (NHS-PEG-S-S-PEG-NHS) linkers. After the nonspecific adsorption sites on the nanoparticle surface are blocked by thiolated PEG (PEG-SH), the lectin-Fe2O3@Au NPs exhibit excellent stability in biological medium and inappreciable cytotoxicity. A series of in vitro and in vivo experiments were then carried out for evaluating the capabilities of three selected lectin (ConA, RCA and WGA)-Fe2O3@Au NPs. The results revealed that the lectin-Fe2O3@Au NPs had a capacity not only for dual mode MR and CT imaging in vitro but also for MR and CT imaging of colorectal cancer in vivo. The experimental results also suggest that lectin could be used as tumor targeting ligand for synthesizing nanoparticle-based contrast agents.

Synthesis of NaYF4 : Yb3+, Er3+@ NaGdF4@ TaOx Multimodal Nanoprobe for Bioimaging Applications

Using solvothermal method, NaYF4:Yb3+, Er3+@ NaGdF4 was synthesized by deposition of a layer of NaGdF4 on the NaYF4: Yb3+, Er3+ upconverting nanoparticles (UCNPs) Then, NaYF4:Yb3+, Er3+@ NaGdF4 @ TaOx core@ shell@ shell nanoparticles were prepared through decorating the radiopaque but fluorescence-transparent TaOx onto the surface of NaYF4:Yb3+, Er3+ @ NaGdF4 by a facile reverse microemulsion strategy. The structure of the NaYF4: Yb3+, Er3+@ NaGdF4@ TaOx nanoparticle was characterized by transmission electron microscopy (TEM), powder X. ray diffraction (XRD), energy. dispersive X. ray analysis (EDS). The X. ray attenuation, magnetic and upconversion luminescent studies suggested that the as. prepared NaYF4:Yb3+, Er3+ @ NaGdF4 @ TaOx nanoparticle could be employed as multimodal nanoprobe for bioimaging applications. Furthermore, the feasibility of NaYF4: Yb3+, Er3+@ NaGdF4 @ TaOx for electronic computer X-ray transaction scan/magnetic resonance imaging (CT/MRI) in vivo was demonstrated. The brightness enhancement of MRI and CT signals in the tumor region were clearly observed at prolonged post. injection to 0. 5 h, indicating that the NaYF4:Yb3+, Er3+@ NaGdF4@ TaOx hold great potential for multimodal imaging in vivo.

Employing Tryptone as a General Phase Transfer Agent to Produce Renal Clearable Nanodots for Bioimaging

Hydrophobic ultrasmall nanoparticles synthesized in nonpolar solvents exhibit great potential in biomedical applications. However, a major challenge when applying these nanomaterials in biomedical research is the lack of a versatile strategy to render them water dispersible while preserving the hydrodynamic diameter (HD) to be less than 8 nm for efficient renal clearance. To address this problem, tryptone is employed as the novel ligand to fabricate a simple, versatile, and inexpensive strategy for transferring hydrophobic NaGdF(4) nanodots (3 nm in diameter) from organic phase into aqueous phase without any complicated organic synthesis. The paramagnetic properties of NaGdF(4) nanodots are well retained after the phase transfer process. In particular, the tryptone-NaGdF(4) nanodots have ultrasmall HD (ca., 7.5 nm), which greatly improves their tumor accumulation and facilitates renal clearance within 24 h postinjection. The as-prepared tryptone-NaGdF(4) nanodots can also be further functionalized with other molecules for extensively biomedical and bioanalytical applications. Furthermore, the proposed strategy can easily be extended to transfer other types of inorganic nanoparticles from hydrophobic to hydrophilic for facilitating biomedical applications.

Renal Clearable Peptide Functionalized NaGdF4 Nanodots for High-Efficiency Tracking Orthotopic Colorectal Tumor in Mouse

The effective delivery of bioimaging probes to a selected cancerous tissue has extensive significance for biological studies and clinical investigations. Herein, the peptide functionalized NaGdF4 nanodots (termed as, pPeptide-NaGdF4 nanodots) have been prepared for highly efficient magnetic resonance imaging (MRI) of tumor by formation of Gd-phosphonate coordinate bonds among hydrophobic NaGdF4 nanodots (4.2 nm in diameter) with mixed phosphorylated peptide ligands including a tumor targeting phosphopeptide and a cell penetrating phosphopeptide. The tumor targeting pPeptide-NaGdF4 nanodots have paramagnetic property with ultrasmall hydrodynamic diameter (HD, c.a., 7.3 nm) which greatly improves their MRI contrast ability of tumor and facilitates renal clearance. In detail, the capability of the pPeptide-NaGdF4 nanodots as high efficient contrast agent for in vivo MRI is evaluated successfully through tracking small drug induced orthotopic colorectal tumor (c.a., 195 mm3 in volume) in mouse.

Fabrication of multifunctional ferric oxide nanoparticles for tumor-targeted magnetic resonance imaging and precise photothermal therapy with magnetic field enhancement

In this study, a biocompatible nanotheranostic platform (termed as Fe2O3@PDA-affibody) has been constructed on the basis of coating a near-infrared light (NIR)-absorbing polydopamine (PDA) shell on oleic acid-capped superparamagnetic ferric oxide nanoparticles (Fe2O3 NPs) using the water-in-oil microemulsion method and then conjugated with affibody ZIGF1R:4551, a peptide with high affinity to tumor and a polyethylene glycol (PEG) stabilizer. The Fe2O3@PDA-affibody integrates T2-weighted magnetic resonance imaging (MRI), tumor-targeting, and magnetic field (MF)-enhanced photothermal therapy (PTT) functionalities into an all-in-one system. The Fe2O3@PDA-affibody shows high negative contrast in the MRI of an SW620 tumor bearing mouse with a decrease of 68% MRI signal, indicating that the Fe2O3@PDA-affibody can recognize tumor with high efficacy and specificity. Furthermore, a high accumulation ratio (>13.5% ID g-1) and enhanced inhibition of tumor growth are achieved under near-infrared (NIR) (808 nm) laser irradiation with the aid of an external MF focused on the targeted tumor, resulting in complete eradication of mouse-borne SW620 tumors without regrowth.

Accurate Monitoring of Renal Injury State through in Vivo Magnetic Resonance Imaging with Ferric Coordination Polymer Nanodots

It is highly challenging to detect the pathophysiology of the diseased kidneys and achieve precise diagnosis because there are few in vivo noninvasive imaging techniques to quantitatively assess kidney dysfunction. This longstanding challenge is normally attributed to the limited molecular contrast agents which can be addressed with renal clearable nanoprobes. In this report, we demonstrate the use of magnetic resonance imaging along with renal clearable ferric coordination polymer nanodots (Fe-CPNDs) for in vivo monitoring the kidney dysfunction effects following drug (daunomycin)-induced kidney injury. After intravenous injection of Fe-CPNDs, the change of the MR signal in the kidney can be precisely correlated with local pathological lesion which is demonstrated by renal anatomic details and biochemical examinations of urine and blood. This finding opens the door to the possibility of noninvasively assessing kidney dysfunction and local injuries.