Human hair derived uPA loaded capsules with dual near-infrared (I and II biowindows) laser responsive capabilities for multi-effective thrombolysis therapy

Abstract

Problems such as massive hemorrhage caused by uncontrolled drug dosage are the main significant obstacles in clinical thrombolytic therapy, which are prominently due to the lack of targeting and controlled release ability of efficient thrombolytic drug systems. In recent years, our team demonstrated that the photothermal effect can facilitate the thrombolytic effect of urokinase plasminogen activator (uPA). However, conventional photothermal agents are relatively expensive or contain heavy metals. If drug delivery systems with low toxicity, minimized heavy metal elements and easy accessibility (preferably provided by human self) can be developed, they will be of value in the future related applications. Herein, uPA-loaded human black hair derived nanoparticles with gelatin capsules (uPA@HBHNP@GNCs) were applied for the first time as a thrombolytic system. Upon irradiation by near-infrared I window (NIR-I) laser or II window (NIR-II) laser, the photothermal effect of HBHNP was triggered to promote the melting of the gelatin encapsulated around the outer layer, thereby realizing the targeted release of uPA. The in vitro and in vivo experiments demonstrated that the deep response to NIR (especially II window) of this system exhibited a satisfactory thrombolytic effect with ideal biosafety. Briefly, the proposed hair derived drug delivery system has the characteristics of human source, low cost, minimum heavy metal components, deep response to NIR (II window) laser, and good biocompatibility, which is expected to be expanded to the treatment for some diseases, even in deep tissue areas.