State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, PR China.
State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing 400716, PR China.
Adv Drug Deliv Rev. 2023 Aug;199:114967. doi: 10.1016/j.addr.2023.114967. Epub 2023 Jun 17.
In patients with compromised immunity, invasive fungal infections represent a significant cause of mortality. Given the limited availability and drawbacks of existing first-line antifungal drugs, there is a growing interest in exploring novel targets that could facilitate the development of new antifungal agents or enhance the effectiveness of conventional ones. While previous studies have extensively summarized new antifungal targets inherent in fungi for drug development purposes, the exploration of potential targets for novel antifungal drug delivery strategies has received less attention. In this review, we provide an overview of recent advancements in new antifungal drug delivery strategies that leverage novel targets, including those located in the physio-pathological barrier at the site of infection, the infection microenvironment, fungal-host interactions, and the fungal pathogen itself. The objective is to enhance therapeutic efficacy and mitigate toxic effects in fungal infections, particularly in challenging cases such as refractory, recurrent, and drug-resistant invasive fungal infections. We also discuss the current challenges and future prospects associated with target-driven antifungal drug delivery strategies, offering important insights into the clinical implementation of these innovative approaches.
在免疫功能受损的患者中，侵袭性真菌感染是导致死亡的重要原因。鉴于现有一线抗真菌药物的有限可用性和缺点，人们越来越关注探索新的靶点，这些靶点可以促进新的抗真菌药物的开发或提高传统药物的疗效。虽然以前的研究已经广泛总结了真菌中固有的用于药物开发的新抗真菌靶点，但针对新型抗真菌药物输送策略的潜在靶点的探索却受到较少关注。在这篇综述中，我们概述了利用新靶点的新型抗真菌药物输送策略的最新进展，这些靶点包括感染部位生理病理屏障、感染微环境、真菌-宿主相互作用以及真菌病原体本身中的靶点。目的是提高治疗效果并减轻真菌感染中的毒性作用，特别是在难治性、复发性和耐药性侵袭性真菌感染等挑战性情况下。我们还讨论了与靶向抗真菌药物输送策略相关的当前挑战和未来前景，为这些创新方法的临床实施提供了重要见解。
