Bridging clinical radiotherapy and space radiation therapeutics through reactive oxygen species (ROS)-triggered delivery.

This review explores the convergence of clinical radiotherapy and space radiation therapeutics, focusing on ionizing radiation (IR)-generated reactive oxygen species (ROS). IR, with high-energy particles, induces precise cellular damage, particularly in cancer treatments. The paper discusses parallels between clinical and space IR, highlighting unique characteristics of high-charge and energy particles in space and potential health risks for astronauts. Emphasizing the parallel occurrence of ROS generation in both clinical and space contexts, the review identifies ROS as a crucial factor with dual roles in cellular responses and potential disease initiation. The analysis covers ROS generation mechanisms, variations, and similarities in terrestrial and extraterrestrial environments leading to innovative ROS-responsive delivery systems adaptable for both clinical and space applications. The paper concludes by discussing applications of personalized ROS-triggered therapeutic approaches and discussing the challenges and prospects of implementing these strategies in clinical radiotherapy and extraterrestrial missions. Overall, it underscores the potential of ROS-targeted delivery for advancing therapeutic strategies in terrestrial clinical settings and space exploration, contributing to human health improvement on Earth and beyond.

Complex Coacervates as a Promising Vehicle for mRNA Delivery: A Comprehensive Review of Recent Advances and Challenges.

Messenger RNA (mRNA)-based therapies have gained significant attention, following the successful deployment of mRNA-based COVID-19 vaccines. Compared with traditional methods of genetic modification, mRNA-based therapies offer several advantages, including a lower risk of genetic mutations, temporary and controlled therapeutic gene expression, and a shorter production time, which facilitates rapid responses to emerging health challenges. Moreover, mRNA-based therapies have shown immense potential in treating a wide range of diseases including cancers, immune diseases, and neurological disorders. However, the current limitations of non-viral vectors for efficient and safe delivery of mRNA therapies, such as low encapsulation efficiency, potential toxicity, and limited stability, necessitate the exploration of novel strategies to overcome these challenges and fully realize the potential of mRNA-based therapeutics. Coacervate-based delivery systems have recently emerged as promising strategies for enhancing mRNA delivery. Coacervates, which are formed by the aggregation of two or more macromolecules, have shown great potential in delivering a wide range of therapeutics due to their ability to form a separated macromolecular-rich fluid phase in an aqueous environment. This phase separation enables the entrapment and protection of therapeutic agents from degradation as well as efficient cellular uptake and controlled release. Additionally, the natural affinity of coacervates for mRNA molecules presents an excellent opportunity for enhancing mRNA delivery to targeted cells and tissues, making coacervate-based delivery systems an attractive option for mRNA-based therapies. This review highlights the limitations of current strategies for mRNA delivery and the advantages of coacervate-based delivery systems to enable mRNA therapeutics. Coacervates protect mRNA from enzymatic degradation and enhance cellular uptake, leading to sustained and controlled gene expression. Despite their promising properties, the specific use of coacervates as mRNA delivery vehicles remains underexplored. This review aims to provide a comprehensive overview of coacervate-mediated delivery of mRNA, exploring the properties and applications of different coacervating agents as well as the challenges and optimization strategies involved in mRNA encapsulation, release, stability, and translation via coacervate-mediated delivery. Through a comprehensive analysis of recent advancements and recommended future directions, our review sheds light on the promising role of coacervate-mediated delivery for RNA therapeutics, highlighting its potential to enable groundbreaking applications in drug delivery and gene therapy.

Knowledge, attitudes, and behaviors related to the fentanyl-adulterated drug supply among people who use drugs in Oregon.

INTRODUCTION: Nonpharmaceutical fentanyl has reconfigured the U.S. illicit drug market, contributing to a drastic increase in overdose drug deaths. While illicit fentanyl has subsumed the drug supply in the Northeast and Midwest, it has more recently reached the West. For this study, we explored knowledge, attitudes, and behaviors among people who use drugs in Oregon in the context of the emergence of fentanyl in the drug supply. METHODS: We conducted in-depth interviews by phone with 34 people who use drugs in Oregon from May to June 2021. We used thematic analysis to analyze transcripts and construct themes. RESULTS: People who use drugs knew about fentanyl, expressed doubt that fentanyl could be found in methamphetamine; believed those who were younger or less experienced were at higher risk for harm; and received information about fentanyl from drug dealers, syringe service programs, or peers (other people who use drugs). Preference for fentanyl's presence in drugs like heroin or methamphetamine was mixed. Some felt that their preference was irrelevant since fentanyl was unavoidable. Participants reported engaging in harm reduction practices, including communicating about fentanyl with dealers and peers, testing for fentanyl, using smaller quantities of drugs, switching from injecting to smoking, and using naloxone. CONCLUSION: People who use drugs are responding to the rise of fentanyl on the West Coast and are concerned about the increasing uncertainty and hazards of the drug supply. They are willing and motivated to adopt harm reduction behaviors. Harm reduction promotion from syringe service programs and public health agencies is essential to reduce injury and death from nonpharmaceutical fentanyl.