Post-marketing safety evaluation of lurbinectedin: a pharmacovigilance analysis based on the FAERS database.

Background: On 15 June 2020, the United States Food and Drug Administration (FDA) approved lurbinectedin for treating adult patients with metastatic small-cell lung cancer whose disease has progressed despite prior platinum-based chemotherapy. Following its market approval, safety data on lurbinectedin in large populations is currently lacking. Therefore, this study aims to evaluate adverse events (AEs) associated with lurbinectedin using the FDA's Adverse Event Reporting System (FAERS)database. Methods: Data concerning lurbinectedin from the FAERS database were extracted for the period from June 2020 to September 2023. Four disproportionality analysis algorithms were utilized to assess potential AEs linked to lurbinectedin: reporting odds ratio (ROR), proportional reporting ratio, disproportionate multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network. These algorithms were applied to quantify signals of lurbinectedin-related AEs. Result: A total of 5,801,535 AE reports were retrieved from the FAERS database, with 511 related to lurbinectedin. These lurbinectedin-induced AEs were observed in 23 system organ classes (SOCs). After simultaneously applying the four algorithms, 47 lurbinectedin-induced AE signals were detected in 23 SOCs. At the SOC level, blood and lymphatic system disorders (ROR, 6.70; 95% confidence interval [CI]: 5.47-8.22) were the only SOC that met all four algorithms. Lurbinectedin's most frequent adverse event was death (ROR: 6.11%, 95% CI: 4.86-7.68), while extravasation exhibited the strongest signal intensity in the ROR algorithm (ROR: 326.37%, 95% CI: 191.66-555.75). Notably, we identified a novel signals: tumor lysis syndrome (ROR: 63.22%, 95% CI: 33.87-117.99). The mean time of onset of AEs was 66 days, the median time of onset was 25 days (interquartile range: 8-64 days), and most AEs occurred within the first month of lurbinectedin treatment. Conclusion: Our study provided a comprehensive evaluation of lurbinectedin's safety profile in the post-marketing setting. In addition to the adverse events consistent with the existing clinical trials and labeling information, we have also identified an unreported signal related to tumor lysis syndrome. This finding will better guide the clinical practice of lurbinectedin and provide valuable evidence for future research.

Conservation of the enzyme-like activity and biocompatibility of CeO2 nanozymes in simulated body fluids.

Cerium oxide nanozymes (CeO2NZs) are attracting vast attention due to their antioxidant and catalytic properties and mimic the activities of multiple endogenous enzymes. However, as is the case for nanomedicines in general, the success in showing their unique medical applications has not been matched by an understanding of their pharmacokinetics, which is delaying their implementation in clinical settings. Furthermore, the data of their modifications in body fluids and the impact on their activity are scarce. Herein, two types of widely used CeO2NZs, electrostatically stabilized and coated with a mesoporous silica shell, were exposed to simulated saliva and lung, gastric and intestinal fluids, and cell culture media. Their physicochemical modifications and bioactivity were tracked over time up to 15 days combining the data of different characterization techniques and biological assays. The results show that the biocompatibility and antioxidant activity are retained in all cases despite the different evolution behaviors in different fluids, including agglomeration. This work provides an experimental basis from a pharmacokinetic perspective that supports the therapeutic effectiveness of CeO2NZs observed in vivo for the treatment of many conditions related to chronic inflammation and cancer, and suggests that they can be safely administered through different portals of entry including intravenous injection, oral ingestion or inhalation.

A microfluidic-based SERS biosensor with multifunctional nanosurface immobilized nanoparticles for sensitive detection of MicroRNA.

Developing sensitive and miniaturized biosensors for the detection of microRNAs (miRNAs) is highly desirable due to their association with early cancer diagnosis and prognosis. Here, a new microfluidic-based biosensor, combined with multifunctional nanosurface and DSN-assisted target recycle amplification strategy, is designed for the detection of miRNA-21. The design of nanosurface includes gold nanoparticles on porous anodic aluminum oxide (AAO) for surface enhanced Raman scattering (SERS) substrate, AuMBA@Ag core-shell nanoparticles for SERS nanotags and single-stranded DNA (ssDNA) in between for miRNA capture and nanotags immobilization. When the target miRNA is present near the nanosurface, it will be captured by ssDNA via hybridization reaction. Then, triggered by the DSN-assisted target recycle process, the freshly formed DNA/miRNA heteroduplexes are cleaved by DSN enzyme into DNA fragments and single-strand miRNA. The SERS nanotags are also dissociated from the nanosurface, leading to decrease of SERS signal. The cleaved target miRNA can be captured and SERS nanotags are released again in the next cycle, resulting in amplification of detection signal. To improve the accuracy of this biosensor, the functionalized AAO membrane is subdivided into two groups - AAO/Au array linked with encoded core-shell SERS nanotags acting as a reactor and primary detector and AAO/Au@Ag array serving as a collector and secondary detector for the dissociative SERS nanotags from the reactor. The decrease of SERS signal in primary detector and increase of signal in secondary detector ensures the accuracy and it is called dual-SERS detection strategy. The detection of miRNA-21 can be achieved with only 30 µL sample and 10 µL enzyme and a wide linear range of 10 fM∼10 nM is obtained. In addition, the microfluidic dual-SERS detection strategy can greatly reduce the possibility of false positive or false negative in single detection mode and it can be applied to the simultaneous detection of multiple miRNAs via integrating different probes.