X. Ji

Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles

In this work, hollow mesoporous silica nanoparticles (HMSNs) with three pore sizes were manufactured to control the drug release rate, and the biological roles of these HMSNs were evaluated in multidrug-resistant (MDR) cancer cells. As novel pore-size-controllable inorganic materials, HMSNs showed negligible cytotoxicity and efficient cellular uptake toward drug-sensitive MCF-7 and drug-resistant MCF-7/ADR cells. Doxorubicin (DOX)-loaded HMSNs (DMSNs) not only demonstrated effective drug loading and a pH-responsive drug release character but also exhibited pore-size-dependent and sustained drug release performance in both in vitro and intracellular drug release experiments. In addition, DMSNs exhibited pore-size-dependent anticancer activity against MCF-7/ADR cells. DMSNs with larger pore size could mediate more cellular uptake of DOX and faster intracellular drug release, which led to more intracellular drug accumulation and stronger MDR-reversal effects. The MDR-overcoming mechanism could be due to the efficient cellular uptake, P-gp inhibition, and ATP depletion. These results demonstrate that HMSNs could be a very promising drug delivery system for pore-size-controllable drug release and cancer MDR reversion.

Manganese oxide-based multifunctionalized mesoporous silica nanoparticles for pH-responsive MRI, ultrasonography and circumvention of MDR in cancer cells

Nano-biotechnology has been introduced into cancer theranostics by engineering a new generation of highly versatile hybrid mesoporous composite nanocapsules (HMCNs) for manganese-based pH-responsive dynamic T(1)-weighted magnetic resonance imaging (MRI) to efficiently respond and detect the tumor acidic microenvironment, which was further integrated with ultrasonographic function based on the intrinsic unique hollow nanostructures of HMCNs for potentially in vitro and in vivo dual-modality cancer imaging. The manganese oxide-based multifunctionalization of hollow mesoporous silica nanoparticles was achieved by an in situ redox reaction using mesopores as the nanoreactors. Due to the dissolution nature of manganese oxide nanoparticles under weak acidic conditions, the relaxation rate r(1) of manganese-based mesoporous MRI-T(1) contrast agents (CAs) could reach 8.81 mM(-1)s(-1), which is a 11-fold magnitude increase compared to the neutral condition, and is almost two times higher than commercial Gd(III)-based complex agents. This is also the highest r(1) value ever reported for manganese oxide nanoparticles-based MRI-T(1) CAs. In addition, the hollow interiors and thin mesoporous silica shells endow HMCNs with the functions of CAs for efficient in vitro and in vivo ultrasonography under both harmonic- and B-modes. Importantly, the well-defined mesopores and large hollow interiors of HMCNs could encapsulate and deliver anticancer agents (doxorubicin) intracellularly to circumvent the multidrug resistance (MDR) of cancer cells and restore the anti-proliferative effect of drugs by nanoparticle-mediated endocytosis process, intracellular drug release and P-gp inhibition/ATP depletion in cancer cells.

Nanohybrid systems of non-ionic surfactant inserting liposomes loading paclitaxel for reversal of multidrug resistance

Three new nanohybrid systems of non-ionic surfactant inserting liposomes loading paclitaxel (PTX) (NLPs) were prepared to overcome multidrug resistance (MDR) in PTX-resistance human lung cancer cell line. Three non-ionic surfactants, Solutol HS 15 (HS-15), pluronic F68 (PF-68) and cremophor EL (CrEL) were inserted into liposomes by film hydration method to form NLPs with an average size of around 110, 180 and 110 nm, respectively. There was an obvious increase of rhodamin 123 (Rh123) accumulation in A549/T cells after treated with nanohybrid systems loading Rh123 (NLRs) when compared with free Rh123 or liposomes loading Rh123 without surfactants (LRs), which indicated the significant inhibition effects of NLRs on drug efflux. The P-gp detection and ATP determination demonstrated that BNLs could not only interfere P-gp expression on the membrane of drug resistant cells, but also decrease ATP level in the cells. The cytotoxicity of NLPs against A549/T cells was higher than PTX loaded liposomes without surfactants (LPs), and the best result was achieved after treated with NLPs2. The apoptotic assay and the cell cycle analysis showed that NLPs could induce more apoptotic cells in drug resistant cells when compared with LPs. These results suggested that NLPs could overcome MDR by combination of drug delivery, P-gp inhibition and ATP depletion, and showed potential for treatment of MDR.

Web-based remote monitoring and control of DAQ for the Daya Bay neutrino experiment

The existing Data Acquisition (DAQ) System of Daya Bay neutrino experiment implemented the run control and run state monitoring through local graphic interface. The quality of network can not completely meet the demands of remote graphic interface operation. In this article, a web-based software was developed to implement the remote real-time monitoring and control of the DAQ system. The software consists of two parts: web server and web services upon DAQ infrastructure. This software was running well since July 2013 and greatly improved the performance of remote operation and shift.