Gaoxin Zhou

A New Near-Infrared Neutral pH Fluorescent Probe for Monitoring Minor pH Changes and its Application in Imaging of HepG2 Cells

A new near-neutral pH near-infrared (NIR) fluorescent probe utilizing a fluorophore–receptor molecular framework that can modulate the fluorescence emission intensity through a fast photoinduced electron transfer process was developed. Our strategy was to choose tricarbocyanine (Cy), a NIR fluorescent dye with high extinction coefficients, as a fluorophore, and N-methylpiperazine (MP) as a receptor. The pH titration indicated that MP-Cy can monitor the minor physiological pH fluctuations with a pKa of ∼7.10 near physiological pH, which is valuable for intracellular pH researches. The probe responds linearly and rapidly to minor pH fluctuations within the range of 3.05–7.10 and exhibits strong dependence on pH changes. As expected, the real-time imaging of cellular pH and the detection of pH in situ was achieved successfully in living HepG2 cells by this probe. It is shown that the probe effectively avoids the influence of autofluorescence and native cellular species in biological systems and meanwhile exhibits high sensitivity, good photostability, and excellent cell membrane permeability.

Redox responsive liposomal nanohybrid cerasomes for intracellular drug delivery.

Cerasome is a freshly developped bilayer vehicle that resemble traditional liposome but has higher mophorlogical stability. In this study, a novel redox-responsive cerasome (RRC) was developed for tumor-targeting drug delivery. The cerasome-forming lipid (CFL) that comprise a cleavable disulfide bond as connector unit of the triethoxysilyl head and the hydrophobic alkyl double chain was synthesized and subsequently used to prepare cerasome through ethanol injection method. RRC that has liposome-resembling lipid bilayer structure was proved being outstanding at drug loading capacity as well as morphological stability as compared to conventional liposomes. In addition, in vitro drug release tests of DOX/RRCs showed a redox-responsive drug release profile: accelerated DOX releasing compared to reduction-insensitive cerasomes (RICs) in the presence of 10mM of GSH. Under the same condition, the reduction sensibility of RRC was further proved by increased hydrodynamic diameter and destroying of integrity from DLS and SEM results. RRC showed non-toxic to human embryonic kidney 293 cells, indicating that this material has good biocompatibility. On the other hand, DOX/RRCs showed a resemble IC50 (half inhibitory concentration) value to that of free DOX to human hepatoma SMMC-7721 cells and breast cancer MCF-7 cells. IC50 values at 48h were found to decrease in the following order: DOX/RIC>DOX/RRC>DOX. Taken together, the RRC developped in this study is of great potential to be utilized as a promising platform for intracellular anticancer drug delivery.

The Synthesis of a Novel Near-Infrared Fluorescent Probe and its Application in Imaging of Living Cells

IR-780, a novel near-infrared (NIR) fluorescent probe, was synthesized and applied to living cells. The probe exhibited good fluorescent characteristic, and cell experiments showed the probe had high affinity and without apparent cytotoxicity. Fluorescent image experiments in living A549 (Human lung adenocarcinoma epithelial cell line) and L929 (mouse fibroblast cell line) cells, further demonstrated its potential applications in biological systems. The probe effectively prevented the influence of autofluorescence and native cellular species in biological systems. It also exhibited excellent cell membrane permeability, good photostability, and high sensitivity.

Liposomally formulated phospholipid-conjugated novel near-infrared fluorescence probe for particle size effect on cellular uptake and biodistribution in vivo

Lipid based nanoparticles (LBNs) with excellent biocompatibility and versatility have received much attention from the drug delivery community recently. A detailed understanding of in vitro and vivo fate of LBNs is important for developing different types of LBNs with improved selectivity and low cytotoxicity. We developed a novel near-infrared (NIR) probe with high fluorescence, designated as DSPE-ir623 (iDSPE). Then, we prepared iDSPE-embeded liposomes (iLPs) with two different hydrodynamic sizes (∼100nm and ∼400nm) to evaluate the effect of particle size on cellular uptake and biodistribution of nanoliposomes in vivo. These iLPs were proved to exhibit good monodispersity, excellent fluorescence and stability. In vitro cell uptake tests demonstrated that iLPs-1 (∼100nm) were taken up more by HT-29 cells than iLPs-2 (∼400nm). Notably, the fluorescence of iLPs can be employed for real-time monitoring of the subcellular locating and its metabolic distribution in vivo. Near-infrared imaging in vivo illustrated that iLPs-1 was mainly accumulated in the tumor tissues, while iLPs-2 was accumulated in liver and spleen. The results indicated that the size of iLPs play an important role in the regulation of intracellular trafficking and biodistribution of liposomes, which also provide a new insight into the development of more effective LBNs. Hence, iDSPE might be a promising tool for the reliable tracing of different types of LBNs.

Synthesis of a near-infrared fluorescent probe and its application in imaging of MCF-7 cells.

IR-789, a novel near-infrared fluorescent probe, was designed, synthesized, and applied to living cells. The probe exhibited better response fluorescence characteristics than the only FDA-approved agent, indocyanine green. Cell experiments showed that the probe had high affinity and without apparent cytotoxicity. Fluorescent image experiments in living MCF-7 cells (human breast adenocarcinoma cell line) further demonstrated the potential applications of the probe in biological systems. The probe effectively prevented the influence of autofluorescence and native cellular species in biological systems. It also exhibited high sensitivity, good photostability, and excellent cell membrane permeability.

Layer-by-layer construction of lipid bilayer on mesoporous silica nanoparticle to improve its water suspensibility and hemocompatibility

Mesoporous silica nanoparticle was expected to provide a versatile drug delivery platform with modification flexibility. To improve its hemocompatibility and realize controlled and/or targeting drug release, modification of bare mesoporous silica nanoparticles is essential. Herein, a novel method of coating mesoporous silica nanoparticles with lipid bilayers was developed. First, a homemade organosiloxane precursor was used for hydrophobic modification of mesoporous silica nanoparticles, then phospholipids (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]) were coated by a filming-rehydration method based on hydrophobic interaction. The nanoparticle samples were characterized by transmission electron microscope, dynamic light scattering, nitrogen sorption, Fourier transform infrared, and thermal gravimetric analysis. Furthermore, the novel lipid bilayer coated mesoporous silica nanoparticles were compared with bare mesoporous silica nanoparticles in terms of suspension stability, drug release, hemolysis, and nonspecific protein absorption. Our data proved that lipid bilayer coated mesoporous silica nanoparticles had better hemobiocompatibility and controlled drug release properties than that of bare mesoporous silica nanoparticles.Graphical Abstract

Design and synthesis of imidazole N–H substituted amide prodrugs as inhibitors of hepatitis C virus replication

Twenty-five novel imidazole N-H substituted Daclatasvir (BMS-790052, DCV) analogues (8a-8y) were designed and synthesized as potential prodrugs. Structure modifications were performed in order to improve potency and pharmacokinetic (PK) properties. All target compounds were evaluated in a hepatitis C virus (HCV) genotype 1b replicon, and the 2-oxoethyl acetate substituted compound 8t showed similar anti-HCV activity (EC50 = 0.08 nM) to that of the lead compound Daclatasvir. Moreover, the utility of prodrug 8t was demonstrated through similar exposure of the parent compound when the prodrugs were dosed in vivo. PK studies showed that prodrug 8t was an ideal candidate for a slower and sustained release form of Daclatasvir.

Synthesis and characterization of a novel near-infrared fluorescent probe for applications in imaging A549 cells

AbstractObjectiveTo design and synthesize a novel near-infrared (NIR) fluorescent probe based on indocyanine Green (ICG), that can be applied in imaging living cells. ResultsA highly fluorescent novel NIR fluorescent probe (IR-793) was synthesized in two steps. IR-793 had better fluorescence and optical stability than ICG. In addition, no obvious cytotoxicity effect of IR-793 was observed and cell viability was above 75% at the maximum concentration (120 nM). IR-793 also exhibited good performance in imaging living A549 cells.ConclusionIR-793, a novel NIR fluorescent probe that is stable, low-cost, highly fluorescent and low cytotoxicity, has been designed and synthesized for imaging living cells.

A novel near-infrared fluorescent probe was synthesized and its application in imaging of living cells

A novel near-infrared fluorescent probe, IR-736, was synthesized and applied to living cells. The probe exhibited good response fluorescent characteristic, and cells experiments showed the probe had high affinity and without apparent cytotoxicity. Fluorescent image experiments in living L929 cells, MCF-7 cells, HepG2 cells, further demonstrated its potential applications in biological systems. The probe effectively prevented the influence of autofluorescence and native cellular species in biological systems. It also exhibited good photostability, and excellent cell membrane permeability.