Fuyin Zheng
Shige Wang
Mingwu Shen
Meifang Zhu
Xiangyang Shi
Electrospun composite nanofibrous scaffolds have attracted much interest for use as drug delivery vehicles in recent years. Herein, we attempted to first encapsulate the anticancer drug doxorubicin (DOX) using inorganic rod-like nano-hydroxyapatite (n-HA) as a carrier. Then, the DOX-loaded n-HA particles were mixed with poly(lactic-co-glycolic acid) (PLGA) solution to fabricate electrospun hybrid nanofibers. The formation of drug-n-HA complexes and the drug-loaded composite nanofibers were characterized using different techniques. In vitro DOX release behavior was examined using UV-vis spectroscopy under both neutral and acidic conditions. The anticancer activity of the drug-loaded composite nanofibers was evaluated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) viability assay and phase contrast microscopic morphology observation of a model KB cancer cell line (a human epithelial carcinoma cell line). We show that DOX can be successfully loaded onto the surface of the n-HA and the formed composite fibers have a uniform and continuous fibrous morphology. Importantly, the loaded DOX shows a sustained release profile, and the released DOX from the nanofibers displays noncompromised antitumor activity towards the growth inhibition of KB cells. With the significantly reduced burst release profile and the improved mechanical durability of the composite nanofiber system compared with n-HA-free PLGA nanofibers, the designed organic-inorganic hybrid nanofibers could be used as a versatile drug delivery system for encapsulation and sustained release of different drugs with prolonged therapeutic efficacy for different biomedical applications.
Benqing Zhou
Zuogang Xiong
Peng Wang
Chen Peng
Mingwu Shen
Serge Mignani
Jean-Pierre Majoral
Xiangyang Shi
We report the construction and characterization of polyethylenimine (PEI)-entrapped gold nanoparticles (AuNPs) chelated with gadolinium (Gd) ions for targeted dual mode tumor CT/MR imaging in vivo. In this work, polyethylene glycol (PEG) monomethyl ether-modified PEI was sequentially modified with Gd chelator and folic acid (FA)-linked PEG (FA-PEG) was used as a template to synthesize AuNPs, followed by Gd(III) chelation and acetylation of the remaining PEI surface amines. The formed FA-targeted PEI-entrapped AuNPs loaded with Gd (FA-Gd-Au PENPs) were well characterized in terms of structure, composition, morphology, and size distribution. We show that the FA-Gd-Au PENPs with an Au core size of 3.0 nm are water dispersible, colloidally stable, and noncytotoxic in a given concentration range. Thanks to the coexistence of Au and Gd elements within one nanoparticulate system, the FA-Gd-Au PENPs display a better X-ray attenuation property than clinical iodinated contrast agent (e.g. Omnipaque) and reasonable r1 relaxivity (1.1 mM−1s−1). These properties allow the FA-targeted particles to be used as an efficient nanoprobe for dual mode CT/MR imaging of tumors with excellent FA-mediated targeting specificity. With the demonstrated organ biocompatibility, the designed FA-Gd-Au PENPs may hold a great promise to be used as a nanoprobe for CT/MR dual mode imaging of different FA receptor-overexpressing tumors.
Xin Li
Lingdan Kong
Wei Hu
Changchang Zhang
Andrij Pich
Xiangyang Shi
Xipeng Wang
Lingxi Xing
Introduction The striking imbalance between the ever-increasing amount of nanomedicines and low clinical translation of products has become the focus of intense debate. For clinical translation, the critical issue is to select the appropriate agents and combination regimen for targeted diseases, not to prepare increasingly complex nanoplatforms. Objectives A safe and efficient platform, α-tocopheryl succinate (α-TOS) married 2D molybdenum disulfide, was devised by a facile method and applied for cooperative imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Methods A novel platform of PEGylated α-TOS and folic acid (FA) conjugated 2D MoS 2 nanoflakes was fabricated for the cooperative multimode computed tomography (CT)/photoacoustic (PA)/thermal imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Results The photothermal efficiency (65.3%) of the platform under safe near-infrared irradiation is much higher than that of other photothermal materials reported elsewhere. Moreover, the covalently linked α-TOS renders platform with selective chemotherapy for cancer cells. Remarkably, with these excellent properties, the platform can be used to completely eliminate the solid tumor by safe photothermal therapy, and then kill the residual cancer cells by selective chemotherapy to prevent tumor recurrence. More significantly, barely side effects occur in the whole treatment process. The excellent efficacy and safety benefits in vivo lead to the prominent survival rate of 100% over 91 days. Conclusion The safe and efficient platform might be a candidate of clinical nanomedicines for multimode theranostics. This study demonstrates an innovative thought in precise nanomedicine regarding the design of next generation of cancer theranostic protocol for potential clinical practice.
Fang Shi
Chen Peng
Yue Yang
Yan Sha
Xiangyang Shi
Haitao Wu
Graphical abstract Highlights • Hep-2 xenograft tumor model and the SLN in rabbits after administration of the PEGylated Au DENPs could be efficient imaged. • The formed PEG-Au DENPs were non-cytotoxic in the given concentration range. • The PEG-Au DENPs could be uptaken predominantly in the lyososomes of the cells. Abstract We report the utilization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for enhanced computed tomography (CT) imaging of human laryngeal squamous carcinoma and indirect CT lymphography imaging in New Zealand rabbits. In this work, PEG-modified amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH 2 ) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The formed PEGylated Au DENPs was used for both enhanced CT imaging of human laryngeal squamous carcinoma cells (Hep-2 cells) and the xenograft tumor mode, and indirect CT lymphography imaging in New Zealand rabbits. In vitro cytotoxicity assay, flow cytometry analysis, and cell morphology observation revealed that the formed PEGylated Au DENPs were non-cytotoxic at a Au concentration up to 400 μM for 24 h and indicated their good biocompatibility. Transmission electron microscopy data confirmed that the PEGylated Au DENPs was uptaken dominantly by the lysosomes of the cells. The PEGylated Au DENPs enabled not only enhance CT imaging of a xenograft tumor model in nude mice after intravenous injection of the particles, but also effective indirect CT lymphography imaging in rabbits. These findings suggest that the designed PEGylated Au DENPs can be used as a potentially effective contrast agent for CT imaging of various biological systems and different kinds of carcinoma, especially lymphatic mapping and human laryngeal squamous carcinoma.
Xiangyang Shi
Yuanyuan Wu
Ding Wang
Juan Su
Jie Liu
Wenxian Yang
Meng Xiao
Wei Tan
Shulong Lu
Jian Zhang
Abstract We demonstrate both theoretically and experimentally that the power density of resonant tunneling diode (RTD) can be enhanced by optimizing emitter spacer layer thickness, in addition to reducing barrier thickness. Compared to the widely used epitaxial structure with ultrathin emitter spacer layer thickness, appropriate increasing the thickness will increase the voltage drop in accumulation region, leading to larger voltage widths of negative differential resistance region. By measuring J-V characteristics, the specific contact resistivity, and the self-capacitance, we theoretically analyze the maximum output power of the fabricated RTDs. It shows that the optimized In 0.8 Ga 0.2 As/AlAs RTD with 20 nm emitter spacer thickness and 5 μm 2 mesa area theoretically possesses the capability to reach 3.1 mW at 300 GHz and 1.8 mW at 600 GHz. Highlights • The power density of resonant tunneling diode can be enhanced by optimizing emitter spacer layer thickness. • The optimized In 0.8 Ga 0.2 As/AlAs RTD possesses the capability to reach 3.1 mW at 300 GHz and 1.8 mW at 600 GHz. • The improved fabrication process based on the previous work can precisely control the mesa area of RTDs. • Optimizing ESL thickness provides an efficient way to balance the cut-off frequency and output power of THz RTD oscillators.
Kangan Li
Mingwu Shen
Lin-feng Zheng
Jinglong Zhao
Qimeng Quan
Xiangyang Shi
Gui-xiang Zhang
We report in vitro and in vivo magnetic resonance (MR) imaging of C6 glioma cells with a novel acetylated 3-aminopropyltrimethoxysilane (APTS)-coated iron oxide nanoparticles (Fe3O4 NPs). In the present study; APTS-coated Fe3O4 NPs were formed via a one-step hydrothermal approach and then chemically modified with acetic anhydride to generate surface charge-neutralized NPs. Prussian blue staining and transmission electron microscopy (TEM) data showed that acetylated APTS-coated Fe3O4 NPs can be taken up by cells. Combined morphological observation; cell viability; and flow cytometric analysis of the cell cycle indicated that the acetylated APTS-coated Fe3O4 NPs did not significantly affect cell morphology; viability; or cell cycle; indicating their good biocompatibility. Finally; the acetylated APTS-coated Fe3O4 nanoparticles were used in magnetic resonance imaging of C6 glioma. Our results showed that the developed acetylated APTS-coated Fe3O4 NPs can be used as an effective labeling agent to detect C6 glioma cells in vitro and in vivo for MR imaging. The results from the present study indicate that the developed acetylated APTS-coated Fe3O4 NPs have a potential application in MR imaging.
Xiangyang Shi
Baiming Deng
Jinguang Deng
Caomin Sun
In relation to the natural electret properties and biological function of collagen, we have studied the bioelectret properties of several kinds of collagen electret membrane, which include I&III collagen, II collagen, the compound membrane of I&III collagen and II collagen and placenta collagen, using a TSDC instrument. We discovered that the defect of a disproportionally high T/sub /spl alpha// can be surmounted after polarizing and improving the method of forming the membrane. Rational complexing of different types of collagen can improve the materials' electret properties to meet clinical medical use.
Xiangyang Shi
Kai Sun
Lajos P. Balogh
James R Baker
FeS nanoparticles (NPs) were synthesized using ethylenediamine core poly(amidoamine) (PAMAM) dendrimers of generation 4 terminated with amino (G4·NH2), hydroxyl (G4·NGlyOH), and carboxyl (G4·SAH) groups, respectively, as stabilizers. These dendrimer-stabilized FeS NPs (FeS DSNPs) were characterized by ultraviolet–visible (UV–vis) spectrometry, zeta-potential measurements, and transmission electron microscopy (TEM). Deposition of FeS NPs onto mesoporous silica gel microparticles was attempted using two approaches: (A) direct coating of {FeS–G4·NH2} DSNPs onto silica particles; and (B) using G4·NH2-coated silica particles to incorporate Fe2; ions for the subsequent formation of FeS NPs. Scanning electron microscopy (SEM) studies show that approach (B) was much more efficient in the incorporation of FeS NPs than approach (A). Such preparation and manipulation of FeS DSNPs provides a unique strategy for fabricating various reactive nanoplatforms for environmental remediation applications.
Xiangyang Shi
Su He Wang
Scott D. Swanson
Song Ge
Zhengyi Cao
Non-invasive diagnosis and detection of early-stage tumors is regarded as one of the current challenges in the biomedical sciences. Magnetic resonance (MR) imaging is a powerful; non-invasive imaging technique because of its high spatial resolution and tomographic capabilities. However; the signal sensitivity of MR imaging for specific biological targets is largely dependent on the specificity and selectivity of the ligand used to target magnetic nanoparticles (NPs) to specific tissues. Development of tumor-targeted magnetic NPs is necessary to enhance the MR signal sensitivity for in-vivo tumor detection. Various proteins such as transferrin; anti-carcinoembryonic antigen monoclonal antibody rch 24; herceptin; and chlorotoxin have been conjugated onto iron oxide NP surfaces. Unfortunately; these protein ligands tend to display immunogenecity and the biological macromolecules used are very expensive and not available for many types of cancer; which thereby limits their applications. One of the most widely used cancer-targeting ligands is folic acid (FA); which targets FA receptors (FAR) that are overexpressed in several human carcinomas including breast; ovary; endometrium; kidney; lung; head and neck; brain; and myeloid cancers. Several groups have investigated the conjugation of folic acid (FA) onto iron oxide NPs for targeting tumor cells. However; many of these reports are limited to in-vitro studies. This is largely a result of difficulties related to the in-vivo stability and
The soybean GH3 gene is transcriptionally induced in a wide variety of tissues and organs within minutes after auxin application. To determine the sequence elements that confer auxin inducibility to the GH3 promoter, we used gel mobility shift assays, methylation interference, deletion analysis, linker scanning, site-directed mutagenesis, and gain-of-function analysis with a minimal cauliflower mosaic virus 35s promoter. We identified at least three sequence elements within the GH3 promoter that are auxin inducible and can function independently of one another. Two of these elements are found in a 76-bp fragment, and these consist of two independent 25and 32-bp auxin-inducible elements. Both of these 25and 32-bp auxin-inducible elements contain the sequence TGTCTC just upstream of an AATAAG. An additional auxininducible element was found upstream of the 76-bp auxin-inducible fragment; this can function independently of the 76-bp fragment. Two TGA-box or Hex-like elements (TGACGTAA and TGACGTGGC) in the promoter, which are strong binding sites for proteins in plant nuclear extracts, may also elevate the level of auxin inducibility of the GH3 promoter. The multiple auxin-inducible elements within the GH3 promoter contribute incrementally to the overall level of auxin induction observed with this promoter.