Single-Photomolecular Nanotheranostics for Synergetic Near-Infrared Fluorescence and Photoacoustic Imaging-Guided Highly Effective Photothermal Ablation.

Multi-modality imaging-guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single-photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT-S) into an amphiphilic lipid, water-dispersible IT-S nanoparticles (IT-S NPs) are prepared. The obtained IT-S NPs have a very simple construction and possess ultra-stable near-infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual-modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT-S NPs are successfully visualized by NIR FL/PA dual-modal imaging. With the comprehensive in vivo imaging information provided by IT-S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT-S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.

Albumin-constrained large-scale synthesis of renal clearable ferrous sulfide quantum dots for T1-Weighted MR imaging and phototheranostics of tumors.

Ultrasmall-sized iron-based nanoparticles are showing increasing potentials to be alternatives as T1-weighted magnetic resonance imaging (MRI) contrast agents to the currently-used gadolinium-based compounds. However, their synthesis particularly in a large-scale and green fashion is still a big challenge. Herein, we report an albumin-constrained strategy to synthesize tiny and highly dispersible ferrous sulfide (termed FeS@BSA) quantum dots (QDs) at ambient conditions. FeS@BSA QDs exhibit ultrasmall size of ca. 3.0 nm with an ultralow magnetization, affording them an appealing longitudinal relaxivity for T1-weighted MRI. The design principle leverages on albumin-mediated biomimetic synthesis and spatial isolation of the protein interface prevents bulk aggregation of the particles. Albumin was found to play crucial roles in the synthesis process: a constrained-microenvironment reactor for particle growth, a water-soluble layer for colloidal stability and a carrier for multi-functionality. This synthetic strategy was found facile, green and particularly large-scalable to 10 L. Mice experiments show good T1-weighted MRI capability of FeS@BSA QDs, significantly lighting the whole body organs, blood vessels and tumors. And interestingly, these QDs can be further used to conduct phototheranostic of tumor benefited from their intense absorption at near-infrared region. In particular, they can be cleared via glomerular filtration into bladder after treatment. Given this approach is biomimetic, scalable and does not require any complicated chemical synthesis or modifications, the method demonstrated here will find great potentials for clinical translation in T1-weighted MRI of diseases and inspire other functional tiny nanoprobes for biomedical applications.

Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication.

Nowadays, nanotechnology is revolutionizing the approaches to different fields from manufacture to health. Carbon nanotubes (CNTs) as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies, due to their excellent physicochemical properties and ability to interface with neurons and neuronal circuits. However, most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs, while neglect their application prospects as therapeutic drugs themselves. At present, the relevant reviews are not available yet. Herein we summarized the latest advances on the biomedical and therapeutic applications of CNTs in vitro and in vivo for neurological diseases treatments as inherent therapeutic drugs. The biological mechanisms of CNTs-mediated bio-medical effects and potential toxicity of CNTs were also intensely discussed. It is expected that CNTs will exploit further neurological applications on disease therapy in the near future.

Fe3O4 Nanoparticles Functionalized with Polymer Ligand for T1-Weighted MRI In Vitro and In Vivo.

Magnetic resonance imaging (MRI) has gained wide interest in early accurate diagnoses due to the high resolution and low toxicity of magnetic nanoparticles. In order to develop potential alternatives of toxic Gd- or Mn-based chelating agents, we report the synthesis of water soluble ultra-small Fe3O4 nanoparticles by a modified co-precipitation method as T1-weighted positive contrast agents. The magnetic iron oxide nanoparticles (MIONs) were functionalized by polymer ligand dodecanthiol-polymethacrylic acid (DDT-PMAA) to enhance their colloidal stability. These MIONs have high longitudinal relaxivity (r1 = 8.18 mM-1·S-1) and exhibited good results in the in vitro and in vivo MR imaging. No toxicity was observed in cytotoxicity assay and histology toxicity analysis. The MIONs@DDT-PMAA(magnetic iron oxide nanoparticles @ dodecanthiol-polymethacrylic acid) present great potential as positive contrast agents for tumor diagnosis.

Blended gold/MnO2@BSA nanoparticles for fluorometric and magnetic resonance determination of ascorbic acid.

A fluorometric and magnetic resonance (MR) dual-modal detection scheme is presented for determination of ascorbic acid (AA). It is based on the use of a blended Au/MnO2@BSA mixture that was prepared via a biomimetic strategy, using bovine serum albumin (BSA) as the template at physiological temperature. The MnO2@BSA fraction (one part of the composite) is not susceptible to MR but can be degraded to MR-active compounds upon a redox reaction with even ultralow concentrations of AA. In parallel, the blended Au/MnO2@BSA recovers its fluorescence because MnO2@BSA acts as a quencher of the fluorescence of circumjacent Au@BSA (the other part of the composite). Fluorescence typically is measured at excitation/emission wavelengths of 470/625 nm. Leveraging on this redox reaction between MnO2 and AA, a dual-mode detection scheme for AA was developed. Both the fluorescence and the MR signal increase with the concentration of AA. The lowest limit for the detection of AA is 0.6 µM in the fluorometric mode and 0.4 µM in the MR mode. Analysis of AA-spiked serum samples showed that the recoveries obtained by either the fluorometric and MR mode can reach 94%. This is the first report of the use of blended nanoparticles with their inherent cross-validation regularity. Graphical abstract Schematic presentation of the biomimetic synthesis of blended Au/MnO2@BSA nanoprobes and fluorometric/MR cross-validation dual-modal detection of ascorbic acid.

2,2'-Dithiodisuccinic acid-stabilized polyion complex micelles for pH and reduction dual-responsive drug delivery.

In this work, a new kind of polyion complex (PIC) micelles with pH and reduction dual responsiveness was developed for effective intracellular drug delivery. The PIC micelles can be readily prepared by mixing a polycationic block polymer, methoxy poly(ethylene glycol)-b-poly(l-lysine) (mPEG-PLL), with a small molecule polyacid, 2, 2'-dithiodisuccinic acid (DTS) in aqueous media. The resultant PIC micelles are of uniform spherical shapes with hydrodynamic radii ranging from 65 to 75 nm based on different feeding ratios of mPEG-PLL and DTS. Interestingly, by using the small molecule polyacid DTS, the obtained PIC micelles show distinct pH-responsive disintegration in acid solution. Meanwhile, the PIC micelles were also assessed to be reduction-responsive due to the presence of disulfide bond in DTS. In view of these stimuli-responsive properties, the potential use of this PIC micelle as smart drug carrier was then investigated. Doxorubicin (DOX), a cationic anticancer drug, was loaded into the PIC micelles with high efficiency. In vitro drug release studies revealed that release of DOX from the PIC micelles was suppressed in neutral solutions due to the stable electrostatic interactions between PIC micelles and DOX, but could be accelerated in acidic solutions or under high GSH condition. Furthermore, flow cytometry and confocal laser scanning microscopy (CLSM) studies indicated that the DOX-loaded PIC micelles could be effectively internalized by MCF-7 human breast cancer cells and release the loaded DOX in intracellular environment. Consequently, the DOX-loaded PIC micelles were capable of inhibiting the proliferation of C26 murine colon cancer and MCF-7 human breast cancer cells in high efficiency, showing similar IC50 values as free DOX. Thus, this biocompatible PIC micelle may be promising for intracellular drug delivery.

A human endogenous protein exerts multi-role biomimetic chemistry in synthesis of paramagnetic gold nanostructures for tumor bimodal imaging.

Protein-mediated biomimetic nanoparticles because of simplicity of their synthesis, subdued nonspecific adsorption, improved pharmacokinetics, and biocompatibility have been receiving increasing attention recently. Nevertheless, only a handful of proteins have been developed for biomimetic synthesis. Worse still, most of them are constrained on single-function usages in chemistry. Exploring new functional proteins, especially those with multi-dentate moieties for multi-role biomimetic chemistry, still remains a substantial challenge. Here, we report on a human endogenous protein, glutathione S-transferase (GST), with favorable amino acid motifs, that has innate talents in incubating high quality gold nanoparticles without adding reducing agents at physiological temperature, and particularly can further anchor gadolinium ions without adding extra chelators. The resultant paramagnetic AuNPs@GSTGd exhibits highly crystallization and uniform size of ca. 10 nm. Compared with clinical contrast agents (Iopamidol, Magnevist), AuNPs@GSTGd shows better imaging performance (e.g. enhanced relaxivity and larger X-ray attenuation efficiency) with clear evidence from Monte Carlo simulation and in vitro experimental results. Further in vivo imaging demonstrates good tumor targeting and clearance of AuNPs@GSTGd without obvious systemic toxicity. Particularly, low immunogenicity of AuNPs@GSTGd is certified by immunological status evaluation of T cells after stimulated with them. This study for the first time demonstrates the manipulation of a human protein for multi-role biomimetic chemistry depending on its unique amino acid motifs and its incorporation into a synthetic agent for potentially addressing some critical issues in cancer nanotheranostics such as synthetic methodology, biocompatibility, function integration, targeting, and immunogenicity.

Effects of enamel matrix derivative on remineralisation of initial enamel carious lesions in vitro.

OBJECTIVE: The purpose of this study was to investigate the effect of enamel matrix derivative on remineralisation of initial enamel carious lesions in vitro. DESIGN: Initial enamel carious lesions were created in bovine enamel blocks in vitro. The lesions were subjected to a pH-cycling regime of 24days. Each daily cycle included 4×3-min applications with one of four treatments: 1g/L NaF aqueous solution (positive control), 6% propylene glycol alginate (PGA) or distilled and deionised water (DDW) (both negative controls), and a gel of enamel matrix derivative and PGA (EMDgel). Samples were subjected to surface microhardness (SMH) testing, polarised light microscopy (PLM) and transverse microradiography (TMR) to measure SMH, mineral loss, lesion depth and mineral content of the surface layer and lesion body before and after pH-cycling. RESULTS: NaF samples showed the highest SMH recovery of all the groups (P<0.05). EMDgel samples showed significantly higher SMH recovery than did PGA ones (P<0.05). NaF samples showed significantly less mineral loss and shallower lesions than all other groups (P<0.05). The DDW and EMDgel samples showed significantly less mineral loss and shallower lesions than PGA samples. Mineral deposition predominated much more at the surface layer in the EMDgel group than in the PGA group (P<0.05). CONCLUSIONS: EMD, the active ingredient of EMDgel, may play an essential role in promoting remineralisation of initial enamel carious lesions. However, EMDgel as a whole did not cause detectable remineralisation of such lesions in vitro.

[Quality assessment on reports of randomized controlled trials of oral and maxillofacial surgery in China].

OBJECTIVE: To evaluate the report quality of randomized controlled trials (RCT) of oral and maxillofacial surgery in China during 2000-2009. METHODS: A comprehensive electronic search was carried out through Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP) and China National Knowledge Infrastructure (CNKI), and 19 kinds of journals of stomatology in China were also hand-searched. We identified RCT published between 2000 and 2009, and classified into oral and maxillofacial surgery and labeled "random" and assessed the quality of these reports using the consolidated standards of reporting trials (CONSORT) statement. RESULTS: 53 RCT articles were included. Reporting quality of the 53 articles was not high and the CONSORT score was 8.2 +/- 2.5. CONCLUSION: The reporting quality of RCT of oral and maxillofacial surgery in China is poor. The CONSORT statement should be used to standardize the reporting of RCT.

[Assessment of reporting quality of randomized controlled trial related to dentine hypersensitivity].

OBJECTIVE: To assess the reporting quality of randomized controlled trials (RCT) related to dentine hypersensitivity which were published between 2000 and 2009 in nineteen Chinese stomatological journals, learn the current status and the influence factors of reporting quality of the dentine hypersensitivity RCT, and determine whether they can provide high quality evidence clinically. METHODS: A handsearching of nineteen Chinese stomatological journals to identify dentine hypersensitivity RCT which were published between 2000 and 2009 and labeled "random". Assess the reporting quality of these RCT by Consolidated Standards of Reporting Trials (CONSORT) statement and then analyze the influence factors of reporting quality by univariate and multivariate analyses. RESULTS: We identified 61 dentine hypersensitivity RCT, among which 45 belonged to journals of Chinese scientific study statistical source and 16 belonged to journals of non-statistical source. The reporting quality of dentine hypersensitivity RCT was not high at large and the CONSORT score was 8.1 +/- 2.4 on average. Multiple linear regression showed that the score of improved Jadad scale (t=4.656, P=0.000) was the main influence factor of reporting quality of dentine hypersensitivity RCT. The better the intrinsic authenticity was, the higher the reporting quality would be. CONCLUSION: Currently, reporting quality of Chinese dentine hypersensitivity RCT needs to be improved. In order to improve the reporting quality of dentine hypersensitivity RCT, experts in stomatology should not only improve experimental design before experiments, but also write papers in accordance with CONSORT statement.