With the increasing global threat of various diseases and infections, it is essential to develop a fast, low-cost, and easy-to-use point-of-care testing (POCT) system for inspections at all levels of medical institutions and self-examination at home. In this work, gold magnetic nanoparticles (GMNPs) are used as the key material, and a rapid visual detection method is designed through integrating loop-mediated isothermal amplification (LAMP) and lateral flow assay (LFA) biosensor for detecting a variety of analytes which includes whole blood, buccal swabs, and DNA. It is worth to note that the proposed method does not need DNA extraction. Furthermore, uracil DNA glycosylase (UDG) is employed to eliminate carrier contamination for preventing false positive results. The whole detection process can be finished within 25 min. The accuracy of detection is measured by assessing the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T. The detection limit of the newly developed extraction-free detection system for MTHFR C677T is 0.16 ng/μL. A preliminary clinical study of the proposed method is carried out by analyzing 600 clinical samples (including 200 whole blood samples, 100 buccal swabs, and 300 genomic DNA samples). The results indicate that the proposed method is 100% consistent with the sequencing results which provides a new choice for POCT and shows a broad application prospect in all levels of medical clinics and at home.

Small biomolecules (m/z < 500) are the material basis of organisms and participate in life activities, but their comprehensive and accurate detection in complex samples remains a challenge. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful detection tool for molecular analysis with high throughput. The development of a new matrix is essential to improve the efficiency of the MALDI-MS for molecular compound detection. In this work, the sandwich-like gold nanoparticles@mesoporous silica nanocomposite@silver nanoparticles (Au@MSN@Ag) nanospheres were prepared by layer-by-layer super-assembly strategy, and can be used as a novel matrix for the quantitative detection and enrichment of small biomolecules by LDI-MS. The sandwich-like nanospheres form a unique plasma resonant cavity that effectively absorbs the laser energy, while the homogeneous mesoporous structure of MSN can lock the analyte, which is essential for efficient LDI of small molecules. Compared to traditional matrices, Au@MSN@Ag shows the advantages of low background, wide application range, high sensitivity, super high salt and protein tolerance, and good stability. For example, the detection limit of glucose was as low as 5 fmol, and showed a good linear relationship in the range of 1−750 μg/mL. Au@MSN@Ag assisted LDI-MS allows the enrichment and detection of small molecules in traditional Chinese medicine (TCM) without derivatization and purification, classification of herbs using the accurate quantitative results oligosaccharides, and identification of gelatin by amino acid content. This research could help in designing more efficient nanostructure matrices and further explored the application of LDI-MS.

Multimodal combinatorial therapy merges different modes of therapies in one platform, which can overcome several clinical challenges such as premature drug loss during blood circulation and significantly improve treatment efficiency. Here we report a combinatorial therapy nanoplatform that enables dual photothermal therapy and pH-stimulus-responsive chemotherapy. By super-assembly of mesoporous silica nanoparticles (MSN) with metal-phenolic networks (MPN), anti-cancer drugs can be loaded in the MSN matrix, while the outer MPN coating allows dual photothermal and pH-responsive properties. Upon near-infrared light irradiation, the MSN@MPN nanoplatform exhibits excellent photothermal effect, and demonstrates outstanding pH-triggered drug release property. In vitro cell experiments suggest the MSN@MPN system exhibits superior biocompatibility and can effectively kill tumor cells after loading anti-cancer drugs. Consequently, the MSN@MPN system shows promising prospects in clinical application for tumor therapy.