•A novel carbon quantum dots (CQDs) has been successfully fabricated by hydrothermal method.•The CQDs proposed exhibits a uniform spherical shape and a narrow size distribution of 8.0 ± 3.0 nm in diameter.•A strong PL emission spectrum centered at 440 nm was observed when it was excited at 300 nm and the quantum yield is 11%.•The CQDs exhibits very low toxicity to NCI-H460 cells in vitro when the concentration is lower than 340.0 mM.•The CQDs have be applied to NCI-H460 cells imaging and tissue section imaging for kidney and liver.Compare to other quantum dots, carbon quantum dots have its own incomparable advantages, such as low cell toxicity, favorable biocompatibility, cheap production cost, mild reaction conditions, easy to large-scale synthesis and functionalization. In this thesis, we took citric acid monohydrate and diethylene glycol bis (3-aMinopropyl) ether as materials, used decomposition method to acquire carbon quantum dots (CQDs) which can emission blue fluorescence under ultraviolet excitation. In the aspect of application, we achieved the biological imaging of CQDs in vivo and in vitro.TEM image (HRTEM inset) of the CQDs prepared.Download high-res image (382KB)Download full-size image

The poor compatibility of carrier materials with drugs is one of the main obstacles in the drug encapsulation of nano-drug delivery system (NDDS), hindering the clinical translation of NDDS. In this study, using paclitaxel (PTX) as the insoluble model drug, we conjugated N,N-diethylniacinamide (DENA), a hydrotropic agent of PTX, to the backbone of poly(L-γ-glutamyl-glutamine) (PGG), a water-soluble polymer, to prepare the “hydrotropic polymer” PGG–DENA to improve its compatibility with PTX. By virtue of the hydrotropic effect of the DENA group, PTX was encapsulated by PGG–DENA to obtain the hydrotropic polymeric nanoparticles (PGG–DENA/PTX NPs). PTX-conjugated poly(L-γ-glutamyl-glutamine) acid (PGG–PTX) NPs previously reported were used as the control in the study. The PGG–DENA/PTX NPs showed a z-average hydrodynamic diameter of about 70 nm, and good long-term stability in PBS solution at 4 °C. The cumulative release rate of PTX from PGG–DENA/PTX NPs reached 79.10% at 96 h, while that of PGG–PTX NPs was 22.96%. PGG–DENA/PTX NPs showed significantly increased in vitro cytotoxicity on NCI-H460 lung cancer cells compared with PGG–PTX NPs. The hemolysis study proved that the PGG–DENA/PTX NPs has good biocompatibility. These results indicated that by introducing the hydrotropic agent DENA, the hydrotropic polymer PGG–DENA becomes an effective carrier material of PTX. This study provides a solution to increase the compatibility of carrier materials with insoluble drugs, and also may provide an effective way to develop a series of personalized carrier materials suitable for different insoluble drugs.

•PTX were successfully loaded on the framework of PGSC and formed a novel conjugate PGSC-PTX.•The size of PGSC-PTX remains in the range of 15–20 nm and its water solubility is 2000-fold higher than PTX.•PGSC-PTX demonstrated sensitive to pH and released PTX rapidly in acid pH.•The potency of PGSC-PTX was comparable to PGG-PTX conjugates against the human lung cancer NH460 cell line in vitro.•The maximum tolerated dose of PGSC-PTX was found to be 250 mg PTX/kg.This study is intended to develop and evaluate a novel, highly water-soluble polymer drug conjugate poly(l-γ-glutamyl-l-carbocisteine)-paclitaxel (PGSC-PTX) which can trigger drug release in tumor acidic microenvironment and improve the therapeutic index of paclitaxel (PTX). PGSC-PTX is formed by introducing an additional carbocisteine into each glutamic side chain of poly(l-glutamic acid)-paclitaxel (PGA-PTX) conjugate. PGSC-PTX self-assembles into nanoparticles, whose size remains in the range of 15–20 nm. PGSC-PTX demonstrated sensitive to pH and released PTX rapidly in low pH. PGSC-PTX shows significant in vitro cytotoxicity to NH460 cancer cell line, which has less toxic and side effect of than PTX. Meanwhile, the hemolytic test indicated that the nanoparticles could be used for intravenous injection. It was concluded that the maximum tolerated dose of PGSC-PTX achieved to be 250 mg PTX/kg, which is extremely maximum tolerated providing a significant foundation in the clinical research.Scheme 1 Synthesis procedure diagram of nano drug PGSC-PTX.The purpose of this study was to develop a novel, highly water-soluble Poly(l-γ-glutamyl-l-carbocisteine)-paclitaxel nanoconjugate (PGSC-PTX) that would improve the therapeutic index of paclitaxel (PTX), PTX were loaded on the framework of PGSC and formed a novel conjugate PGSC-PTX with 36% (w/w) loading capacity. PGSC-PTX self-assembles into nanoparticles, whose size remains in the range of 15–20 nm and its water solubility was 60 mg/mL, which is 2000-fold higher than PTX. PGSC-PTX demonstrated sensitive to pH and released PTX rapidly in acid pH. When tested in vitro against the human lung cancer NH460 cell line, the potency of PGSC-PTX was comparable to PGG-PTX conjugates. The IC50 for PGSC-PTX was almost equal to PGG-PTX. The maximum tolerated dose of PGSC-PTX was found to be 250 mg PTX/kg. (This result indicates that PGSC-PTX was substantially more effective in vivo than PGG-PTX.)Download high-res image (81KB)Download full-size image

To determine the influence of physicochemical properties of lipid nanoparticles (LNPs) carrying siRNA on their gene silencing in vivo. Mechanistic understanding of how the architecture of the nanoparticle can alter gene expression has also been studied.The effect of 3-N-[(ω-methoxypoly(ethylene glycol)2000)carbamoyl]-1,2-dimyristyloxy-propylamine (PEG-C-DMA) on hepatic distribution and FVII gene silencing was determined. FVII mRNA in hepatocytes and liver tissues was determined by Q-PCR. Hepatic distribution was quantified by FACS analysis using Cy5 labeled siRNA.Gene silencing was highly dependent on the amount of PEG-C-DMA present. FVII gene silencing inversely correlated to the amount of PEG-C-DMA in LNPs. High FVII gene silencing was obtained in vitro and in vivo when the molar ratio of PEG-C-DMA to lipid was 0.5 mol%. Surprisingly, PEGylation didn’t alter the hepatic distribution of the LNPs at 5 h post administration. Instead the amount of PEG present in the LNPs has an effect on red blood cell disruption at low pH.Low but sufficient PEG-C-DMA amount in LNPs plays an important role for efficient FVII gene silencing in vivo. PEGylation did not alter the hepatic distribution of LNPs, but altered gene silencing efficacy by potentially reducing endosomal disruption.

A novel method for the synthesis of water-soluble CdSe and CdSe/CdS quantum dots (QDs) under the assistance of high-intensity ultrasonic irradiation is reported. As-prepared CdSe/CdS QDs were characterized by X-ray powder diffraction and high-resolution transmission electronmicroscopy. The absorption and fluorescence emission spectra were measured to investigate the effect of CdS passivation on the electronic structure of the quantum dots. After the growth of CdS shell, the photoluminescence quantum yields of CdSe/CdS core–shell quantum dots increased three times more than that of the original CdSe QDs. The QDs were successfully used for the fluorescence imaging of cells and blood capillary.Graphical abstractA novel method for the synthesis of water-soluble small-size CdSe and CdSe/CdS quantum dots under high-intensity ultrasonic irradiation has been reported. As-prepared CdSe/CdS QDs were about 5.0 nm with narrow size distribution. The products were well formed which have been characterized by X-ray powder diffraction and high-resolution transmission electronmicroscopy as shown in Fig. a and b. Optical absorption and fluorescence emission spectra were used to probe the effect of CdS passivation on the electronic structure of the quantum dots. The photoluminescence quantum yields of CdSe/CdS core–shell quantum dots were larger than the original CdSe by around 3 times. The QDs were successfully used for the fluorescence imaging of cells and blood capillary.Highlights► High-quality CdSe and CdSe/CdS QDs have be prepared with ultrasonic-assistance. ► The ultrasonic irradiation facilitate the formation of the CdSe/CdS QDs. ► The quantum yield of core–shell nanocrystals is about 3 times that of the original nanocrystals. ► The cell viability is relative to concentration of QDs and kinds of cells. ► Imaging of cells and tissues can be obtained by the strategy proposed.

Toxicities of CdSe and CdSe/CdS quantum dots (QDs) synthesized by ultrasound-assisted methods were investigated in vitro and in vivo. Five human cell lines were used to assess the cytotoxicity of as-prepared CdSe and CdSe/CdS by assays of MTT viability, red blood cell hemolysis, flow cytometry, and fluorescence imaging. The results show that these QDs may be cytotoxic by their influence in S and G2 phases in cell cycles. The cytotoxicity of QDs depends on both the physicochemical properties and related to target cells.