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Abstract: Ultrasound (US) imaging is one of the most common biomedical imaging methods, due to the easy assessment and noninvasive way. For more precise and accurate US imaging, many contrast agents have been developed in a form of microbubbles composed of inner gas and shell materials. However, microbubbles showed undesirable short half-life under acoustic field during US imaging and insufficient in vivo stability in blood flow due to diffusion or bubble destruction. Therefore, the improvement of the half-life and stability of microbubbles under in vivo condition is highly needed for long-term in vivo US imaging. Herein, we developed rationally designed gas-generating polymeric microsphere (GGPM) that can produce microbubbles without encapsulation of gas for long-term and continuous US imaging. The poly(cholesteryl γ-butyrolactone-b-propylene oxide), poly(CB-PO), with carbonate side chains was synthesized as gas-generating polymer by ring-opening polymerization of cholestryl γ-butyrolactone (CB) and propylene oxide (PO). As optimal structure for intense US signal generation, porous GGPMs (p-GGPMs) with the average size about 3–5 μm were prepared with poly(CB-PO) by double emulsion method. These p-GGPMs generated continuous US signals over 70 min, while the signals from Sonovue®, a commercial US contrast agent were completely attenuated within 15 min. This long-term signal duration of p-GGPM was also reproduced when they were subcutaneously injected under the skin of mouse. Moreover, as advanced in vivo application, the fine US imaging of heart in rat was enabled by intravenous injection of p-GGPM. Therefore, these overall results showed the great potential of p-GGPM as gas-generating US contrast agent for in vivo biomedical imaging and diagnosis. [Copyright &y& Elsevier]

The self-organizing complexes with hyaluronic acid (HA) and polydopamine (PDA), an adhesion mediator via hydrogen bonding, were investigated for use as protein drug carriers. The complexes were prepared with HA of different molecular weights (20 kDa and 200 kDa) and various molar ratios of dopamine and lysozyme, a model protein. Dopamine-conjugated HA (HADA)/PDA complexes were prepared by one-pot synthesis by relying on the self-polymerization of dopamine under oxidative, weakly basic conditions. Lysozyme was bound via coacervation and hydrogen bonding into HADA/PDA complexes. Complex diameters were 100–300 nm, based on transmission electron microscopy image and dynamic light scattering findings. Circular dichroism and differential scanning calorimetry showed that a stable protein formulation was obtained without degradation while preserving the thermal characteristics of lysozyme. Transition temperature ( T m ) of the HADA/PDA/lysozyme complex (1:10:0.05 ratio) was 72.45 °C, which is close to the T m of the native lysozyme (72.46 °C). The efficacy of complexes was also evaluated to protect the structural stability of lysozyme. Lysozyme (0.33 mol) was complexed with HA monomer; consequently, lysozyme activity in the HADA/PDA complex was not affected from short-term degradation. Protein encapsulation and efficacy of the formulations showed successful complexation as protein carriers, thus suggesting an effective combinatory protein delivery system. [ABSTRACT FROM AUTHOR]

Abstract We report that the ordered structure in the assemblies of iron oxide nanoparticles in conjugated polymer nanoparticles is the key to achieve better properties to realize multimodal theranostic agents for magnetic resonance and photoacoustic imaging. Hybrid nanoparticles of a conjugated polymer (PCPDTBT), a phospholipid (D8PE) with a primary amine polar head, and iron oxide (Fe 3 O 4) nanoparticles were prepared by a phase-separated film shattering process by varying the iron oxide concentration while maintaining a fixed mixing ratio of PCPDTBT and D8PE. Notably, the hybrid nanoparticles assembled at a molar mixing ratio of 1:1:0.8 (PCPDTBT/D8PE/Fe 3 O 4) exhibited the shortest transversal relaxation time, T 2 , and a photoacoustic signal 22 times higher than that obtained at the 1:1:0 mixing ratio. Structural analysis by X-ray diffraction together with the measurements of energy transfer by transient absorption spectroscopy confirmed that the structural ordering of these hybrid nanoparticles was responsible for their enhanced photoacoustic and magnetic properties. Graphical abstract Image 1 Highlights • Hybrid nanoparticles of a donor-acceptor-type conjugated polymer, iron oxides and a phospholipid. • Shattering of phase-separated films produced hybrid nanoparticles. • Strongly ordered assembly structures were confirmed by grazing incidence X-ray scattering. • Contrast in both photoacoustic and magnetic resonance imaging were significantly enhanced. • Ordering and clustering of conjugated polymers and magnetites were responsible for the property enhancement. [ABSTRACT FROM AUTHOR]

One of the newly emerging carbon materials, nanodiamond (ND), has been exploited for use in traditional electric materials and this has extended into biomedical and pharmaceutical applications. Recently, NDs have attained significant interests as a multifunctional and combinational drug delivery system. ND studies have provided insights into granting new potentials with their wide ranging surface chemistry, complex formation with biopolymers, and combination with biomolecules. The studies that have proved ND inertness, biocompatibility, and low toxicity have made NDs much more feasible for use in real in vivo applications. This review gives an understanding of NDs in biomedical engineering and pharmaceuticals, focusing on the classified introduction of ND/drug complexes. In addition, the diverse potential applications that can be obtained with chemical modification are presented. [ABSTRACT FROM AUTHOR]

The development of improved electrocatalysts for the oxygen reduction reaction (ORR) is a key to achieving green energy conversion and storage. In this study, heterogeneous amorphous nanoonions were derived from nanodiamonds by thermal annealing and subsequently doped with nitrogen by hydrothermal and pyrolytic methods as potential catalytic supports. Electrocatalytic activity and capacity of the nanocomposites with gold nanorods were significantly modulated for the ORR, depending on heteroatom N configuration into the nanoonions. AuNR/ N-doped nanoonion composite having chemical composition of rich pyridinic and low amine N exhibited mainly first-order linear kinetics, indicating four-electron transfer toward the ORR. AuNR/hydrothermally N-doped nanoonions composite having high pyrrolic and lower pyridinic N affected the pseudocapacitance. The interfacial interaction between gold and amorphous nanoonion provided facilitated electronic transfer on the heterojunction and thus, electrocatalytic activity were critically affected by N configuration-dependent nanoonoin for ORR. The N-doped nanoonions reported herein are a potential platform to develop diverse metal composites with electrocatalytic functions by providing excellent conductivity and resistance to gold decomposition. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Antiangiogenic peptide drugs have received much attention in the fields of tumor therapy and tumor imaging because they show promise in the targeting of integrins such as αvβ3 on angiogenic endothelial cells. However, systemic antiangiogenic peptide drugs have short half-lives in vivo, resulting in fast serum clearance via the kidney, and thus the therapeutic effects of such drugs remain modest. In this study, we prepared self-assembled glycol chitosan nanoparticles and explored whether this construct might function as a prolonged and sustained drug delivery system for RGD peptide, used as an antiangiogenic model drug in cancer therapy. Glycol chitosan hydrophobically modified with 5β-cholanic acid (HGC) formed nanoparticles with a diameter of 230nm, and RGD peptide was easily encapsulated into HGC nanoparticles (yielding RGD-HGC nanoparticles) with a high loading efficiency (>85%). In vitro work demonstrated that RGD-HGC showed prolonged and sustained release of RGD, lasting for 1 week. RGD-HGC also inhibited HUVEC adhesion to a βig-h3 protein-coated surface, indicating an antiangiogenic effect of the RGD peptide in the HGC nanoparticles. In an in vivo study, the antiangiogenic peptide drug formulation of RGD-HGC markedly inhibited bFGF-induced angiogenesis and decreased hemoglobin content in Matrigel plugs. Intratumoral administration of RGD-HGC significantly decreased tumor growth and microvessel density compared to native RGD peptide injected either intravenously or intratumorally, because the RGD-HGC formulation strongly enhanced the antiangiogenic and antitumoral efficacy of RGD peptide by affording prolonged and sustained RGD peptide delivery locally and regionally in solid tumors. [Copyright &y& Elsevier]