Accurate and dynamic visualization of vascular diseases can contribute to restraining the further deterioration of diseases in a timely manner. However, it is still unable to precisely determine whether and to what extent blood vessels or brain tissues are damaged. Here we report novel BBTD-based NIR-II fluorophores HY1-HY4 with highly twisted structures (55 o at the S 0 state), extremely strong aggregation-induced emission (AIE) characteristics (I/I 0 > 13), and remarkably high fluorescence QYs (up to 14.45%) in the NIR-II region (> 1000 nm) and ~ 0.27% in the NIR-IIb window (> 1500 nm) in aqueous solution. Using NIR-IIb AIE HY4 dots, high-resolution NIR-IIb fluorescence imaging of revascularization and thrombolysis, and real-time feedback of the therapeutic efficacy of Chinese medicine DXI on ischemic stroke, were achievedfor the first time. In addition, results showed that DXI conferred neuroprotection against cerebral ischemia injury mediated via the angiogenesis pathway. These attractive results provide a new perspective for designing ultra-bright NIR-IIb probes for the vascular-related phenomena, disease assessment, and precise intraoperative imageguided therapy with a deeper tissue penetration depth and higher resolution.

Exosomal miRNAs play a critical role in cancer biology and could be potential biomarkers for cancer diagnosis. However, due to the low abundance of miRNAs in the exosomes, recognizing and detecting disease-associated exosomal miRNAs in an easy-to-operate way remain a challenge. Herein, we used a liposome-mediated membrane fusion strategy (MFS) to transfect CRISPR/Cas13a into exosomes, termed MFS-CRISPR, directly measuring exosomal miRNAs in plasma. Using the MFS-CRISPR platform for detection of the exosomal miR-21, we achieve a linear range spanning four orders of magnitude (104–108 particles/mL) and the method is able to detect the exosomal miR-21 in as low as 1.2 × 103 particles/mL. The liposome-mediated MFS could confine fluorescent signals in fused vesicles, which can be used for exosome heterogeneity analysis. Moreover, MFS-CRISPR assay was evaluated by measuring clinical samples, and the difference of miR-21 expression of breast cancer patients and healthy donors was significant. Because of high sensitivity and simplicity, the proposed method could have promising clinical potential for cancer diagnosis and treatment monitoring.

Exosomes, a subgroup of extracellular vesicles secreted by multiple cells, have great potential as cancer biomarkers in clinical applications. However, enrichment and detection of exosomes from complex media remains a...

Overcoming multiple biological barriers, including circulation time in vivo, tumor vascular endothelium, reticuloendothelial system (RES), extracellular matrix (ECM), etc., is the key to improve the therapeutic efficacy of drug delivery systems in treating tumors. Inspired by the ability of natural erythrocytes to cross multiple barriers, in this study, a biomimetic delivery system named NE@DOX-Ang2 was developed for enhancing the chemotherapy of breast cancer, which employed nano-erythrocyte (NE) encapsulating doxorubicin (DOX) and surface modification with a targeted angiopep-2 peptide (Ang2). NE@DOX-Ang2 enhanced the capacity to cross biological barriers in a three-dimensional (3D) tumor spheroid model and in vivo in mice. Compared with a conventional drug delivery system of liposomes, the half-life of NE@DOX-Ang2 increased approximately 2.5 times. Moreover, NE@DOX-Ang2 exhibited excellent tumor-targeting ability and antitumor effects in vitro and in vivo. Briefly, the prepared nano-erythrocyte drug carrier has features of favorable biocompatibility and low immunogenicity and the advantage of prolonging the half-life of drugs, which may provide a novel perspective for development of clinically available nanomedicines.