Thrombolysis Combined Therapy Using CuS@SiO2-PEG/uPA Nanoparticles

Abstract

Massive hemorrhage caused by the uncontrolled release of thrombolysis drugs is a key issue of thrombolysis therapy in clinical practice. In this study, we report a near-infrared (NIR) light-triggered drug delivery system, i.e., CuS@mSiO2-PEG (CSP) nanoparticles, for the loading of a thrombolytic drug (urokinase plasminogen activators, uPA). CSP nanoparticles with the CuS nanoparticles as photothermal agents and mesoporous SiO2 for the loading of uPA were synthesized using a facile hydrothermal method. The CSP core-shell nanoparticles were demonstrated to possess excellent photothermal performance, exhibiting a photothermal conversion efficiency of up to 52.8%. Due to the mesoporous SiO2 coating, the CSP core-shell nanoparticles exhibited appropriate pore size, high pore volume, and large surface area; thus, they showed great potential to be used as drug carriers. Importantly, the release of uPA from CuS@mSiO2-PEG/uPA (CSPA) carriers can be promoted by the NIR laser irradiation. The drug loading content of uPA for the as-prepared NIR-triggered drug delivery system was calculated to be 8.2%, and the loading efficiency can be determined to be as high as 89.6%. Due to the excellent photothermal effect of CSP nanocarriers, the NIR-triggered drug delivery system can be used for infrared thermal imaging in vivo. The in vivo thrombolysis assessment demonstrated that the NIR-triggered drug delivery system showed excellent thrombolytic ability under the irradiation of an 808 nm laser, showing the combined therapy for thrombolysis. As far as we know, the CSPA core-shell nanoparticles used as NIR-triggered drug delivery systems for thrombolysis have not been reported.

P-Selectin mediates targeting of a self-assembling phototherapeutic nanovehicle enclosing dipyridamole for managing thromboses

“…As previously reported, the clinical use of DIP in thrombotic treatment increases the risk of severe bleeding [ 68 ]. Massive hemorrhaging attributed to the uncontrolled release of thrombolytic drugs is a crucial issue in thrombus treatment in clinical practice [ 69 ]. The enrichment provided by DIP-FU-PPy-NPs resulted in augmented DIP delivery, increased thrombolytic efficacy, and a reduced risk of hemorrhaging.…”

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis

“…25,26 Specifically, mesoporous silica nanoparticles (MSNs) offer excellent stability, good biocompatibility, a large specific surface area, and convenient modification, thus having been recognized as effective biocompatible carriers for loading CuS nanoparticles and enhancing their overall biocompatibility. 26,27 Moreover, the release of silicon ions from MSNs has the capacity to enhance osteogenic differentiation and accelerate osteogenesis in periodontal tissues. 28 Another noteworthy biomolecule is sulfated chitosan (SCS), a polysaccharide derived from chitosan through sulfation at the C-2 and C-6 positions with sulfonic groups (−SO 3 − ).…”

“…Nanoparticles possess unique antibacterial mechanisms against various bacterial species due to their substantial surface area and high charge density. ,, They can effectively penetrate deep into periodontal pockets and inflamed gingiva, enabling deep sterilization. , Copper sulfide (CuS) nanoparticles have received considerable attention in promoting angiogenesis and osteogenesis for periodontitis therapy, , as they can release copper ions to induce the generation of reactive oxygen species (ROS) via Fenton-like reactions, leading to bacterial death. ,, Additionally, they act as essential catalysts for vascular endothelial growth factor (VEGF) and inhibit active bone resorption, contributing to angiogenesis and osteogenesis. , Considering the potential toxicity of CuS nanoparticles at high concentrations, various approaches involving surface modification and incorporation of biomolecules have been explored to improve their biocompatibility. , Specifically, mesoporous silica nanoparticles (MSNs) offer excellent stability, good biocompatibility, a large specific surface area, and convenient modification, thus having been recognized as effective biocompatible carriers for loading CuS nanoparticles and enhancing their overall biocompatibility. , Moreover, the release of silicon ions from MSNs has the capacity to enhance osteogenic differentiation and accelerate osteogenesis in periodontal tissues . Another noteworthy biomolecule is sulfated chitosan (SCS), a polysaccharide derived from chitosan through sulfation at the C-2 and C-6 positions with sulfonic groups (−SO 3 – ).…”

Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation

“…In addition, poly(3,4-ethylenedioxythiophene) PEDOT, a conducting polymer, has attracted considerable attention in biomedical applications due to its biodegradability, easy modification, biocompatibility, good absorption of NIR, and high photothermal and photoelectric conversion. 21−23 NIR-mediated nonpharmacological thrombolytic strategies are developing due to their ability to overcome the inadequacy of thrombolytic medicines; 24 however, many phototherapies (PT) are still limited in their usage due to several factors such as a lack of specific resistance to photobleaching, accumulation, and a short in vivo lifespan. 14−16 Currently, several anticoagulants, including rivaroxaban heparin, and warfarin, are being used to inhibit the formation of thrombus and blood clots in clinics.…”

“…NIR-mediated nonpharmacological thrombolytic strategies are developing due to their ability to overcome the inadequacy of thrombolytic medicines; however, many phototherapies (PT) are still limited in their usage due to several factors such as a lack of specific resistance to photobleaching, accumulation, and a short in vivo lifespan. − Currently, several anticoagulants, including rivaroxaban heparin, and warfarin, are being used to inhibit the formation of thrombus and blood clots in clinics . Heparin increases the affinity of thrombin with antithrombin III for inactivating thrombin; however, the use of heparin increases the risk of bleeding and immune-arbitrated thrombocytopenia .…”