PhAc-ALGP-Dox

Opioids are the primary regimens for perioperative analgesia with controversial effects on oncological survival. The underlying mechanism remains unexplored. This study developed survival-related gene co-expression networks based on RNA-seq and clinical characteristics from TCGA cohort. Two survival-related networks were identified, and drug-induced transcriptional profiles were predicted. Immune cell infiltration algorithm, least absolute shrinkage and selection operator (LASSO) regression, and cox proportional models were executed to explore the correlation between opioid-related drugs and prostate cancer patient prognosis. The opioid receptor agonists, represented by tramadol, were evidenced for anti-survival effects on prostate cancer by facilitating the DNA replication and cell cycle, and immune cell infiltration. Conversely, opioid receptor antagonists showed pro-survival effects. A novel prognostic model containing CNIH2, MCCC1, and Gleason scores was established and validated in two independent cohorts. This study revealed opioids' effect on prostate cancer progression, and provided a novel model to predict these regulations in clinical outcomes.

Extracellular vesicles (EVs) are an experimental class of drug carriers. Alternative sources of EVs are currently being explored to overcome limitations related to their manufacturing from mesenchymal stem cells. In this work, Citrus limon-derived EVs were tested as carriers for the widely used chemotherapeutic drug - doxorubicin (DOX). Capillary electrophoresis (CE) and nanoplasmonic sensing (NPS) were developed for the quality control of DOX-EV preparations. It was found that the CE method enables simultaneous detection of free and incorporated DOX and allows assessing the stability of the preparations and the drug leakage. NPS, on the other hand, demonstrated that DOX is accumulated in the interfacial region of the carrier. The activity of DOX-loaded EVs was tested on HeLa (cervical cancer cells) and HEK293T (human embryonic kidney cells) cell lines. It was found that DOX incorporation into plant-derived EVs virtually does not affect the drug's cytotoxicity to HeLa cells but significantly decreases DOX activity against HEK293T cell line.