Micro- and nano-carrier systems: The non-invasive and painless local administration strategies for disease therapy in mucosal tissues.

Mucus is a viscoelastic and adhesive obstacle which protects vaginas, eyes and other mucosal surfaces against foreign pathogens. Numerous diseases that affect the mucosa could be afforded prophylactic and therapeutic treatments with fewer systemic side effects if drugs and genes could be sufficiently delivered to the target mucosal tissues. But drugs and genes are trapped effectively like other pathogens and rapidly removed by mucus clearance mechanism. The emergence of micro- and nano-delivery technologies combined with the realization of non-invasive and painless administration routes brings new hope for the treatment of disease. For retained drugs and genes to mucosal tissues, carriers must increase retention time in the mucus to make full contact with epithelial cells and be transported to target tissues. This review focuses on the current development of micro- and nano-carriers to improve the localized therapeutic efficiency of targeted and sustained drug and gene delivery in mucosal tissues.

High-performance fluorescence-encoded magnetic microbeads as microfluidic protein chip supports for AFP detection.

Fluorescence-encoded magnetic microbeads (FEMMs), with the fluorescence encoding ability of quantum dots (QDs) and magnetic enrichment and separation functions of Fe3O4 nanoparticles, have been widely used for multiple biomolecular detection as microfluidic protein chip supports. However, the preparation of FEMMs with long-term fluorescent encoding and immunodetection stability is still a challenge. In this work, we designed a novel high-temperature chemical swelling strategy. The QDs and Fe3O4 nanoparticles were effectively packaged into microbeads via the thermal motion of the polymer chains and the hydrophobic interaction between the nanoparticles and microbeads. The FEMMs obtained a highly uniform fluorescent property and long-term encoding and immunodetection stability and could be quickly magnetically separated and enriched. Then, the QD-encoded magnetic microbeads were applied to alpha fetoprotein (AFP) detection via sandwich immunoreaction. The properties of the encoded microspheres were characterized using a self-designed detecting apparatus, and the target molecular concentration in the sample was also quantified. The results suggested that the high-performance FEMMs have great potential in the field of biomolecular detection.

Reverse Fluorescence Enhancement and Colorimetric Bimodal Signal Readout Immunochromatography Test Strip for Ultrasensitive Large-Scale Screening and Postoperative Monitoring.

Ultrasensitive and quantitative fast screening of cancer biomarkers by immunochromatography test strip (ICTS) is still challenging in clinic. The gold nanoparticles (NPs) based ICTS with colorimetric readout enables a quick spectrum screening but suffers from nonquantitative performance; although ICTS with fluorescence readout (FICTS) allows quantitative detection, its sensitivity still deserves more efforts and attentions. In this work, by taking advantages of colorimetric ICTS and FICTS, we described a reverse fluorescence enhancement ICTS (rFICTS) with bimodal signal readout for ultrasensitive and quantitative fast screening of carcinoembryonic antigen (CEA). In the presence of target, gold NPs aggregation in T line induced colorimetric readout, allowing on-the-spot spectrum screening in 10 min by naked eye. Meanwhile, the reverse fluorescence enhancement signal enabled more accurately quantitative detection with better sensitivity (5.89 pg/mL for CEA), which is more than 2 orders of magnitude lower than that of the conventional FICTS. The accuracy and stability of the rFICTS were investigated with more than 100 clinical serum samples for large-scale screening. Furthermore, this rFICTS also realized postoperative monitoring by detecting CEA in a patient with colon cancer and comparing with CT imaging diagnosis. These results indicated this rFICTS is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

An ultra-sensitive and colorimetric sensor for copper and iron based on glutathione-functionalized gold nanoclusters.

Here, we report an ultra-sensitive and colorimetric sensor for the detection of Fe3+ or Cu2+ successively using glutathione-functionalized Au nanoclusters (GSH-AuNCs). For GSH-AuNCs can catalytically oxidize peroxidase substrates, such as 3, 3', 5, 5'-tetramethylbenzidine (TMB), colored products are formed in the presence of H2O2. While upon the addition of Fe3+ or Cu2+ into the GSH-AuNCs-TMB-H2O2 system, diverse color and absorbance of the system was obtained due to the self oxidation of Fe3+ and the inhibition of peroxidase-like activity of GSH-AuNCs. With the introduction of ethylene diamine tetraacetic acid (EDTA) or ammonium fluoride (NH4F) to GSH-AuNCs-TMB-H2O2+Cu2+ system or GSH-AuNCs-TMB-H2O2+Fe3+ system respectively, a restoration of color and absorbance of system was realized. On the basis of above phenomenon, a colorimetric and quantitative approach for detecting Fe3+ and Cu2+ was developed with detection limit of 1.25 × 10-9 M and 1.25 × 10-10 M respectively. Moreover, the concentration of Fe3+ and Cu2+ in human serums was also accurate quantified by this method. So this design strategy realized the simple and simultaneous detection of Fe3+ and Cu2+, suggesting significant potential in clinical diagnosis.