Vancomycin-conjugated polydopamine-coated magnetic nanoparticles for molecular diagnostics of Gram-positive bacteria in whole blood.

BACKGROUND: Sepsis is caused mainly by infection in the blood with a broad range of bacterial species. It can be diagnosed by molecular diagnostics once compounds in the blood that interfere with molecular diagnostics are removed. However, this removal relies on ultracentrifugation. Immunomagnetic separation (IMS), which typically uses antibody-conjugated silica-coated magnetic nanoparticles (Ab-SiO2-MNPs), has been widely applied to isolate specific pathogens in various types of samples, such as food and environmental samples. However, its direct use in blood samples containing bacteria is limited due to the aggregation of SiO2-MNPs in the blood and inability to isolate multiple species of bacteria causing sepsis. RESULTS: In this study, we report the synthesis of vancomycin-conjugated polydopamine-coated (van-PDA-MNPs) enabling preconcentration of multiple bacterial species from blood without aggregation. The presence of PDA and van on MNPs was verified using transmission electron microscopy, X-ray photoelectron spectroscopy, and energy disruptive spectroscopy. Unlike van-SiO2-MNPs, van-PDA-MNPs did not aggregate in the blood. Van-PDA-MNPs were able to preconcentrate several species of Gram-positive bacteria in the blood, lowering the limit of detection (LOD) to 10 colony forming units/mL by polymerase chain reaction (PCR) and quantitative PCR (qPCR). This is 10 times more sensitive than the LOD obtained by PCR and qPCR using van-SiO2-MNPs. CONCLUSION: These results suggest that PDA-MNPs can avoid aggregation in blood and be conjugated with receptors, thereby improving the sensitivity of molecular diagnostics of bacteria in blood samples.

A pH-activated charge convertible quantum dot as a novel nanocarrier for targeted protein delivery and real-time cancer cell imaging.

The rapid developments of nanocarriers based on quantum dots (QDs) have been confirmed to show substantial promise for drug delivery and bioimaging. However, optimal QDs-based nanocarriers still need to have their controlled behavior in vitro and in vivo and decrease heavy metal-associated cytotoxicity. Herein, a pH-activated charge convertible QD-based nanocarrier was fabricated by capping multifunctional polypeptide ligands (mPEG-block-poly(ethylenediamine-dihydrolipoic acid-2,3-dimethylmaleic anhydride)-L-glutamate, PEG-P(ED-DLA-DMA)LG) onto the surface of core/multishell CdSe@ZnS/ZnS QD by means of a ligand exchange strategy, followed by uploading of cytochrome C (CC) (CC-loaded QD-PEG-P(ED-DLA-DMA)LG) via electrostatic interactions, in which QDs that were water-soluble and protein-loading were perfectly integrated. That is, the CC-loaded QD-PEG-P(ED-DLA-DMA)LG inherited excellent fluorescence properties from CdSe@ZnS/ZnS QD for real-time imaging, as well as tumor-microenvironment sensitivities from PEG-P(ED-DLA-DMA)LG for enhanced cellular uptake and CC release. Experimental results verified that the QD-PEG-P(ED-DLA-DMA)LG showed enhanced internalization, rapid endo/lysosomal escape, and supplied legible real-time imaging for lung carcinoma cells. Furthermore, pH-triggered charge-convertible ability enabled the QD-PEG-P(ED-DLA-DMA)LG-CC to effectively kill cancer cells better than did the control groups. Hence, constructing smart nanocomposites by facile ligand-exchange strategy is beneficial to QD-based nanocarrier for tumor-targeting cancer therapy.

Multifunctional hyaluronic acid-mediated quantum dots for targeted intracellular protein delivery and real-time fluorescence imaging.

The use of multifunctional quantum dots (QDs) as smart nanocarriers has exhibited substantial promise for imaging, targeting and therapeutic functionalities. Here, we describe the synthesis of green-light emitting CdZnSeS/ZnS quantum dots (QDs) combined with redox-sensitive hyaluronic acid ligand (hyaluronic acid-disulfide-linked poly(ethylene glycol)-histamine-diethylenetriamine, HA-PEG(SS)-His-Diet) for the targeted intracellular delivery of protein drugs. The generation of HA-PEG(SS)-His-Diet-QD exhibits monodispersity with high quantum yield, negligible cytotoxicity and long-term stability at pH 7.4 and 5.5. These HA-PEG(SS)-His-Diet-QDs could effectively immobilize cytochrome C (CC) with high loading efficiency, enable target of CD44-overexpressing MCF-7 human breast tumor cells, and accelerate protein release under high intracellular glutathione concentration condition. The HA-PEG(SS)-His-Diet-QD act as a promising nanocarrier for enhanced endo/lysosomal escape, targeted delivery of proteins and real-time cellular imaging. In addition, CC-loaded-HA-PEG(SS)-His-Diet-QD could effectively induce the CD44-positive cancer cells apoptosis in vitro. Ultimately, this redox-sensitive and fluorescent QD-based nanocarrier has shown major promise for targeted intracellular protein transport.