Targeted delivery of chemodrugs to tumor sites is highly desirable for efficient chemotherapy. Extracellular vesicles (EVs)-based carrier is an ideal candidate for drug delivery in cancer therapy. However, the insufficient tumor-targeting capability remains to be solved. Herein, we designed an aptamer circuit with cascade recognition capacity to guide the vesicles for tumor targeting. The sequential signal transduction triggered by the specific binding between aptamers and their targets leads to the preferential binding of vesicles with cancerous cells rather than noncancerous cells with fewer targets. Moreover, a self-promoted tumor-targeting loop induced by Doxorubicin Hydrochloride (DOX) released from vesicles further amplified the targeting capability of the vesicle-based drug carrier to tumor sites through up-regulating PDL1 marker on the surface of tumor cells. Ultimately, the accumulation of DOX in tumor cells resulted in the immunogenic cell death (ICD) for evoking anti-tumor immune response. Overall, this work presents a self-promoted tumor-targeting strategy for vesicle-based carrier by coupling the cascade recognition and tumor-targeting loop, which improves the therapeutic effect of immunogenic chemotherapy.
Shuxuan Shao, Cao Zhang, Wei Du et al.· Small Methods· 0 citations
Early diagnosis of acute diseases is fundamentally constrained by the lack of chemically tractable methods for biomarker discovery directly from a complex plasma. Here, we report PSABD (plasma-SELEX-enriched aptamer-based biomarker discovery and diagnosis), a chemical platform that integrates carboxylate magnetic-bead-mediated plasma protein capture within situ aptamer SELEX, enabling molecular-recognition-driven identification of disease-associated biomarkers. With this strategy, enriched aptamers not only serve as affinity probes but also function as structurally programmable molecular handles to pull down their targets, thereby linking selection chemistry with proteomic discovery. With acute myocardial infarction (AMI) as a model, PSABD identified malate dehydrogenase 2 (MDH2) as an unexpected AMI-associated plasma protein, which was significantly elevated in AMI patient samples and exhibited a high binding affinity to selected aptamers. On the basis of this interaction, we developed an aptamer-based analytical platform capable of distinguishing AMI patients from healthy individuals. Collectively, PSABD establishes a general chemical strategy that bridges molecular recognition, biomarker discovery, and diagnostic development, highlighting aptamers as programmable chemical probes for the acute disease diagnosis and clinical translation.
circDesign is presented, an algorithm that explicitly incorporates IRES structural deviation into circRNA sequence design while jointly optimizing codon adaptation and thermodynamic stability and establishes IRES structural preservation as a mechanistic design principle for circRNA engineering and position circDesign as a rational framework for therapeutic circRNA development.
Congcong Xu, F. Jiang, Yifan Jiang et al.· Angewandte Chemie· 0 citations