Improved double emulsion technology for fabricating autofluorescent microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents

The aim of this study is to explore an improved double emulsion technology with in situ reaction of lysine (Lys) and glutaraldehyde (GA) for fabricating autofluorescent Lys-poly(lactic-co-glycolic acid)-GA (Lys-PLGA-GA) microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents. Scanning electron microscope (SEM) and static light scattering (SLS) results show that 80% of the Lys-PLGA-GA microcapsules are larger than 1.0 mu m and 90% of them are smaller than 8.9 mu m. SEM and laser confocal scanning microscope (LCSM) data demonstrate that the structure of our Lys-PLGA-GA microcapsules is hollow. Compared with the FT-IR spectrum of PLGA microcapsules, a new peak at 1644 cm(-1) in that of Lys-PLGA-GA microcapsules confirms the formed Schiff base in Lys-PLGA-GA microcapsules. LCSM images and fluorescence spectra show that our Lys-PLGA-GA microcapsules exhibit bright and stable autofluorescence without conjugation to any fluorescent agent, which can be ascribed to the n-pi* transitions of the C=N bonds in the formed Schiff base. Our autofluorescent Lys-PLGA-GA microcapsules might have more wide applications than traditional fluorescent dyes because their excitation and emission spectra are both broad. The fluorescence intensity can also be tuned by the feeding amount of Lys and GA. The MTT assays reveal that the autofluorescent microcapsules are biocompatible. The results of fluorescent imaging in cells and in vitro ultrasonic imaging demonstrate the feasibility of our autofluorescent Lys-PLGA-GA microcapsules as ultrasonic/fluorescent dual-modality contrast agents. This novel ultrasonic/fluorescent dual-modality contrast agent might have potential for a variety of biological and medical applications. (C) 2014 Elsevier B.V. All rights reserved

Silica-coated super-paramagnetic iron oxide nanoparticles (SPIONPs): a new type contrast agent of T-1 magnetic resonance imaging (MRI)

Magnetic resonance imaging (MRI), a sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has an intrinsic advantage in safety compared with radiotracer and optical imaging modalities; however, MRI contrast agents are less sensitive than complexes used in other imaging techniques. Usually the clinically used Gd-based complexes MRI-T-1 contrast agents are toxic; therefore, the demand for nontoxic novel T-1-weighted MRI candidates with ultrasensitive imaging and advanced functionality is very high. In this research, silica-coated ultra-small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via a thermal decomposition method, which demonstrated themselves as a high performance T-1-weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses. Transmission electron microscopy (TEM) results illustrated that the diameter of the SPIONPs was in the range of 4 nm and the average size of Fe3O4@SiO2 was about 30-40 nm. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the phase purity of the prepared SPIONPs. These magnetite nanoparticles exhibited a weak magnetic moment at room temperature because of the spin-canting effect, which promoted a high positive signal enhancement ability. MTT assays and histological analysis demonstrated good biocompatibility of the SPIONPs in vitro and in vivo. In addition, the silica-coated ultrasmall (4 nm sized) magnetite nanoparticles exhibited a good r(1) relaxivity of 1.2 mM(-1) s(-1) and a low r(2)/r(1) ratio of 6.5 mM(-1) s(-1). In vivo T-1-weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of the as-synthesized magnetite nanoparticles. These results reveal silica-coated SPIONPs as a promising candidate for a T-1 contrast agent with extraordinary capability to enhance MR images

A Y-1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer

A Y-1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cance

A novel fibroblast activation protein-targeted near-infrared fluorescent off-on probe for cancer cell detection, &ITin vitro&IT and &ITin vivo &ITimaging

A new hemicyanine-based fibroblast activation protein-targeted near-infrared fluorescent probe is designed and it shows high selectivity and sensitivity to cancer cell detection, and in vitro and in vivo imaging. This probe is successfully applied in fluorescence detection of living cells (with a detection limit of 1500 cells per mL). It is believed that many new functions or distributions of FAP could be discovered by this new probe later

Dual ATP and pH responsive ZIF-90 nanosystem with favorable biocompatibility and facile post-modification improves therapeutic outcomes of triple negative breast cancer in vivo

Dual ATP and pH responsive ZIF-90 nanosystem with favorable biocompatibility and facile post-modification improves therapeutic outcomes of triple negative breast cancer in viv

Neuropeptide Y Y-1 receptor-mediated biodegradable photoluminescent nanobubbles as ultrasound contrast agents for targeted breast cancer imaging

Targeted molecular imaging has attracted great attention in cancer diagnosis and treatment. However, most clinically used ultrasound contrast agents (UCAs) are non-targeted microbubbles seldom used for cancer imaging. Here, we fabricated fluorescent nanobubbles (NBs) by encapsulation of liquid tetrade-cafluorohexane (C6F14) within biodegradable photoluminescent polymers (BPLPs) through an emulsion evaporation process and conjugation of PNBL-NPY ligand for specific targeting of Y-1 receptors overexpressed in breast tumors. The developed PNBL-NPY modified NBs were uniform in size with good dispersibility and photostability, presenting good ultrasound enhancement. Further, in vitro and in vivo results indicated that the fabricated NBs exhibit high affinity and specificity to Y-1 receptor-overexpressing breast cancer cells and tumors with minimal toxicity and damage to organs. Our developed PNBL-NPY-modified NBs are novel targeted UCAs for safe, efficient and specific targeted breast cancer imaging, and may provide a new nanoplatform for early cancer diagnosis and treatment in the future. (C) 2016 Elsevier Ltd. All rights reserved

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Multifunctional photosensitizer-conjugated core-shell Fe3O4@NaYF4:Yb/Er nanocomplexes and their applications in T2-weighted magnetic resonance/upconversion luminescence imaging and photodynamic therapy of cancer cells

Due to non-invasive deep imaging and therapy, multifunctional agents of magnetic resonance (MR)/ upconversion luminescence (UCL) imaging and photodynamic therapy (PDT) play an important role in clinical diagnosis and treatment of cancers, and also in the assessment of therapy effect. In this paper, tetra-sulfonic phthalocyanine aluminium (AlPcS4) photosensitizers-conjugated Fe3O4@NaYF4:Yb/Er (NPs- AlPcS4) nanocomplexes were synthesized for the T2-weighted MR/UCL imaging and PDT of cancer cells. The PEG-coated Fe3O4@NaYF4:Yb/Er nanoparticles (NPs) with a core–shell structure showed strong T2- weighted MR relaxivity (r2 = 42.131 mM21 s21) and UCL emission in the visible region (the bands at about 654–674 nm, 545 nm and 524 nm), and were conjugated successfully with AlPcS4 photosensitizer by electrostatic interaction. By direct observation of XFM and staining with Prussian blue, the element distribution and location of NPs in MCF-7 cells were characterized, respectively. Under irradiation from a 980 nm laser, the death ratio of MCF-7 cells incubated with NPs-AlPcS4 nanocomplexes could be up to about 70%. The results indicated that the as-prepared NPs-AlPcS4 nanocomplexes would be a potential candidate as multifunctional nanoprobes for the dual-modal T2-weighted MR/UCL imaging and PDT of cancers in the future