55 research outputs found
Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents
No full textMagnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents. © 2015 American Chemical Society143461sciescopu
A General Strategy for Site-Directed Enzyme Immobilization by Using NiO Nanoparticle Decorated Mesoporous Silica
No full textMesoporous materials have recently gained much attention owing to their large surface area, narrow pore size distribution, and superior pore structure. These materials have been demonstrated as excellent solid supports for immobilization of a variety of proteins and enzymes for their potential applications as biocatalysts in the chemical and pharmaceutical industries. However, the lack of efficient and reproducible methods for immobilization has limited the activity and recyclability of these biocatalysts. Furthermore, the biocatalysts are usually not robust owing to their rapid denaturation in bulk solvents. To solve these problems, we designed a novel hybrid material system, mesoporous silica immobilized with NiO nanoparticles (SBA-NiO), wherein enzyme immobilization is directed to specific sites on the pore surface of the material. This yielded the biocatalytic species with higher activity than free enzyme in solution. These biocatalytic species are recyclable with minimal loss of activity after several cycles, demonstrating an advantage over free enzymes. Site-directed enzyme immobilization onto the pore surface of NiO nanoparticle decorated mesoporous silica (SBA) leads to a species with higher activity than the free enzyme in solution (see figure). These biocatalysts are recyclable with minimal loss of activity after five cycles, demonstrating an advantage over free enzymes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.118211sciescopu
Responsive Assembly of Upconversion Nanoparticles for pH‐Activated and Near‐Infrared‐Triggered Photodynamic Therapy of Deep Tumors
No full textUpconversion nanoparticle (UCNP)-mediated photodynamic therapy has
shown great effectiveness in increasing the tissue-penetration depth of
light to combat deep-seated tumors. However, the inevitable phototoxicity
to normal tissues resulting from the lack of tumor selectivity remains as a
major challenge. Here, the development of tumor-pH-sensitive photodynamic
nanoagents (PPNs) comprised of self-assembled photosensitizers grafted pHresponsive
polymeric ligands and UCNPs is reported. Under neutral pH conditions,
photosensitizers aggregated in the PPNs are self-quenched; however,
upon entry into a tumor microenvironment with lower pH, the PPNs not only
exhibit enhanced tumor-cell internalization due to charge reversal but also are
further disassembled into well-dispersed nanoparticles in the endo/lysosomes
of tumor cells, enabling the efficient activation of photosensitizers. The results
demonstrate the attractive properties of both UCNP-mediated deep-tissue
penetration of light and high therapeutic selectivity in vitro and in vivo.© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
Highly Sensitive Diagnosis of Small Hepatocellular Carcinoma Using pH-Responsive Iron Oxide Nanocluster Assemblies
No full textIron oxide nanoparticle (IONP)-based
magnetic resonance imaging
(MRI) contrast agents have been widely used for the diagnosis of hepatic
lesions. However, current IONP-based liver-specific MRI contrast agents
rely on single-phase contrast enhancement of the normal liver, which
is not sensitive enough to detect early stage small hepatocellular
carcinomas (HCCs). We herein report i-motif DNA-assisted pH-responsive
iron oxide nanocluster assemblies (termed RIAs), which provide an
inverse contrast enhancemt effect to improve the distinction between
normal liver and target HCC tissues. The acidic pH of the tumor microenvironment
triggers the disassembly of the RIAs, which leads to a drastic decrease
in their relaxivity ratio (r2/r1), thus converting the RIAs from a T2 to T1
contrast agent. This inverse contrast enhancement of normal liver
darkening and HCC brightening under T1 imaging mode was validated
on an orthotopic HCC model. Our design provides a novel strategy for
the exploitation of the next-generation intelligent MRI contrast agents
Expression of B and T Lymphocyte Attenuator in Patients with Severe Community-Acquired Pneumonia and the Effect of Steroid Therapy in a Mouse Model
No full textRenal-Clearable Hollow Bismuth Subcarbonate Nanotubes for Tumor Targeted Computed Tomography Imaging and Chemoradiotherapy
No full textAlthough metallic nanomaterials with high X-ray attenuation coefficients have been widely used as X-ray computed tomography (CT) contrast agents, their intrinsically poor biodegradability requires them to be cleared from the body to avoid any potential toxicity. On the other hand, extremely small-sized nanomaterials with outstanding renal clearance properties are not much effective for tumor targeting because of their too rapid clearance in vivo. To overcome this dilemma, here we report on the hollow bismuth subcarbonate nanotubes (BNTs) assembled from renal-clearable ultrasmall bismuth subcarbonate nanoclusters for tumor-targeted imaging and chemoradiotherapy. The BNTs could be targeted to tumors with high efficiency and exhibit a high CT contrast effect. Moreover, simultaneous radio- and chemotherapy using drug-loaded BNTs could significantly suppress tumor volumes, highlighting their potential application in CT imaging-guided therapy. Importantly, the elongated nanotubes could be disassembled into isolated small nanoclusters in the acidic tumor microenvironment, accelerating the payload release and kidney excretion. Such body clearable CT contrast agent with high imaging performance and multiple therapeutic functions shall have a substantial potential for biomedical applications. © 2018 American Chemical Societ
Differential expression profile analysis of DNA damage repair genes in CD133+/CD133− colorectal cancer cells
No full textFunctional assembly of protein fragments induced by spatial confinement.
No full textNatural proteins are often confined within their local microenvironments, such as three-dimensional confinement in organelles or two-dimensional confinement in lipid rafts on cytoplasmic membrane. Spatial confinement restricts proteins' entropic freedom, forces their lateral interaction, and induces new properties that the same proteins lack at the soluble state. So far, the phenomenon of environment-induced protein functional alteration still lacks a full illustration. We demonstrate here that engineered protein fragments, although being non-functional in solution, can be re-assembled within the nanometer space to give the full activity of the whole protein. Specific interaction between hexahistidine-tag (His-tag) and NiO surface immobilizes protein fragments on NiO nanoparticles to form a self-assembled protein "corona" on the particles inside the nanopores of mesoporous silica. Site-specific assembly forces a shoulder-by-shoulder orientation and promotes fragment-fragment interaction; this interaction together with spatial confinement of the mesopores results in functional re-assembly of the protein half fragments. To our surprise, a single half fragment of luciferase (non-catalytic in solution) exhibited luciferase activity when immobilized on NiO in the mesopores, in the absence of the complimentary half. This shows for the first time that spatial confinement can induce the folding of a half fragment, reconstitute the enzyme active site, and re-gain the catalytic capability of the whole protein. Our work thereby highlights the under-documented notion that aside from the chemical composition such as primary sequence, physical environment of a protein also determines its function
Porous hollow palladium nanoplatform for imaging-guided trimodal chemo-, photothermal-, and radiotherapy
No full textNano‐bio interactions between 2D nanomaterials and mononuclear phagocyte system cells
No full textAbstract Two‐dimensional (2D) nanomaterials, known for their unique atomic arrangements and exceptional physicochemical properties, have garnered significant attention in biomedical applications, particularly in the realms of immunotherapy for tissue engineering and tumor therapy. These applications necessitate a thorough assessment of the potential influence of 2D nanomaterials on immune cells. Notably, the mononuclear phagocyte system (MPS) cells, which play pivotal roles in both innate and adaptive immunity, are essential for maintaining organismal homeostasis. MPS cells with phagocytic capability contribute to the prevention of foreign body invasion and the elimination of dead or senescent cells. Furthermore, MPS cells, including macrophages and dendritic cells, serve as vital bridges between innate and adaptive immune responses. Therefore, understanding the nano‐bio interactions between 2D nanomaterials and MPS cells is imperative. These nano‐bio interactions including cellular uptake, cytocompatibility, and immunological impact are invaluable for the purposeful design of 2D nanomaterials. Herein, we provide an overview of the latest advancements in understanding the nano‐bio interactions between 2D nanomaterials and MPS cells, and discuss the current challenges and future prospects of employing 2D nanomaterials in the field of nanomedicine
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