A size-controllable and facile synthetic strategy has been developed to fabricate a series of hollow mesoporous silica nanoparticles (HMSNs) with tunable hollow cores or shell thicknesses by employing gold nanoparticles (Au NPs) and cetyltrimethylammonium bromide (CTAB) as dual templates. Various sizes of Au NPs and different amounts of tetraethyl orthosilicate contributed to structure-tailored mesoporous silica-coated Au NPs. After calcination, CTAB molecules were completely removed, and Au NPs could still support the silica shell due to the high melting point. HMSNs were ultimately obtained by etching Au NPs. Applications of HMSNs as nanocarriers for delivering drugs were investigated. Significantly, it was flexible and convenient to control drug-loading/releasing behavior of HMSNs just by tuning the hollow cores or shell thicknesses. Intracellular experiments have proven that HMSNs are suitable for delivering drugs. We anticipate that this study could provide an important avenue for the synthesis of HMSNs and further contribute to advancing practical applications of HMSNs in drug delivery systems.

The exosome has emerged as a promising noninvasive biomarker for the early diagnosis of cancer. Therefore, it is highly desirable to develop simple, inexpensive, and user-friendly biosensors for convenient, sensitive, and quantitative exosome assay. Herein, we developed a simple and cost-efficient electrochemical biosensor by combining a metal−organic framework (MOF)functionalized paper and a screen-printed electrode (SPE) for portable, ultrasensitive, and quantitative determination of cancer-derived exosomes. In principle, the biosensor relied on recognition of the exosome by Zr-MOFs and aptamer to initiate the hybridization chain reaction (HCR) and the formation of DNAzyme for signal amplification. Benefiting from the high signal amplification ability of HCR, the label-free paper-based biosensor is capable of ultrasensitive exosome assay with a detection limit down to 5 × 10 3 particles/ mL, which is superior to that of most reported methods. Moreover, the proposed paper-based biosensor possessed the advantages of low cost, simple operation, and high sensitivity, making it affordable and deliverable for point-of-care (POC) diagnosis in resource-limited settings.

Tumor exosomes are promising biomarkers for early cancer diagnosis in a noninvasive manner. However, precise capture and direct analysis of tumor-specific exosomes in complex biological samples are still challenging. Herein, we present a highly efficient dual-aptamer recognition system for precisely isolating and quantifying tumor exosomes from the complex biological environment based on hyperbranched DNA superstructure-facilitated signal amplification and ratiometric dual-signal strategies. When tumor exosomes were captured by the dual-aptamer recognition system, the cholesterol-modified DNA probe was anchored on the surface of the exosomes, activating DNA tetrahedron-based hyperbranched hybridization chain reaction to generate a sandwich complex. Then, the sandwich complex could bind a large number of Ru­(NH3)6 3+ (Ru­(III)), leading to a small amount of unbound Ru­(III) left in the supernatant after magnetic separation. Hence, the redox reaction between Ru­(II) and [Fe­(CN)6]3– (Fe­(III)) was significantly prevented, causing an obviously enhanced I Fe(III)/I Ru(III) value. Consequently, highly sensitive detection of tumor exosomes was achieved. The developed approach successfully realized direct isolation and analysis of tumor exosomes in complex sample media and human serum samples as well. More significantly, this ratiometric dual-signal mode and immobilization-free strategy effectively circumvented the systematic errors caused by external factors and the tedious probe immobilization processes, thus displaying the excellent performances of high reliability, improved accuracy, and easy manipulation. Overall, this approach is expected to offer novel ways for nondestructive early cancer diagnosis.

Abnormal pH values in the organelles are closely associated with inappropriate cellular functions and many diseases. Monitoring subcellular pH values and their variations is significant in biological processes occurring in living cells and tissues. Herein, we develop a series of ratiometric fluorescence nanoprobes for quantification and imaging of pH values with a single-wavelength excitation in cytoplasm, lysosomes, and mitochondria. The nanoprobes consist of mesoporous silica nanoparticles assembled with aminofluorescein as the recognition unit for pH measurement and ethidium bromide as reference fluorophore. Further conjugation of subcellular targeting moiety enables the nanoprobes to specifically target lysosome and mitochondria. Confocal fluorescence imaging demonstrated that the nanoprobes could effectively monitor the pH fluctuations from 5.0 to 8.3 in living cells by ratio imaging with 488 nm excitation. Subcellular pH determination and imaging in lysosome and mitochondria could also be achieved in different conditions. The current method can offer a general strategy to determine subcellular analytes and investigate the interactions in biological samples.

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