Direct delivery of plasmin using clot-anchoring thrombin-responsive nanoparticles for targeted fibrinolytic therapy

Sun, Michael; Pontius, M. Hao Hao; Yang, S.Q.; Pendekanti, Tejal; Raghunathan, Shruti; Shavit, Jordan A.; Gupta, Anirban Sen

doi:10.1016/j.jtha.2022.11.037

Cited by 8 publications

(3 citation statements)

References 57 publications

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“…In addition, the presence of AP (pH 7.4 + AP and pH 6.5 + AP) resulted in an even greater release rate of uPA (52.1% at pH 6.5 in 1 h), indicating that the release of uPA was attributed to both Pkr(Ca/Pda-uPA)-cRGD’s pH responsiveness and selective binding capacity to AP. This could be supported by published studies [ 42 , 43 ].…”

Section: Resultssupporting

confidence: 84%

pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis

Ye,

Chen,

Zhang

et al. 2024

Research

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Thrombosis can cause life-threatening disorders. Unfortunately, current therapeutic methods for thrombosis using injecting thrombolytic medicines systemically resulted in unexpected bleeding complications. Moreover, the absence of practical imaging tools for thrombi raised dangers of undertreatment and overtreatment. This study develops a theranostic drug carrier, Pkr(IR-Ca/Pda-uPA)-cRGD, that enables real-time monitoring of the targeted thrombolytic process of deep vein thrombosis (DVT). Pkr(IR-Ca/Pda-uPA)-cRGD, which is prepared from a Pickering-emulsion-like system, encapsulates both near-infrared-II (NIR-II) contrast agent (IR-1048 dye, loading capacity: 28%) and urokinase plasminogen activators (uPAs, encapsulation efficiency: 89%), pioneering the loading of multiple drugs with contrasting hydrophilicity into one single-drug carrier. Upon intravenous injection, Pkr(IR-Ca/Pda-uPA)-cRGD considerably targets to thrombi selectively (targeting rate: 91%) and disintegrates in response to acidic thrombi to release IR-1048 dye and uPA for imaging and thrombolysis, respectively. Investigations indicate that Pkr(IR-Ca/Pda-uPA)-cRGD enabled real-time visualization of targeted thrombolysis using NIR-II imaging in DVT models, in which thrombi were eliminated (120 min after drug injection) without bleeding complications. This may be the first study using convenient NIR-II imaging for real-time visualization of targeted thrombolysis. It represents the precision medicine that enables rapid response to acquire instantaneous medical images and make necessary real-time adjustments to diagnostic and therapeutic protocols during treatment.

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Section: Resultssupporting

confidence: 84%

pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis

Ye,

Chen,

Zhang

et al. 2024

Research

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“…TTR experiments showed that the nanoparticles could effectively dissolve fibrin and re-dredge blood vessels (Figure 5C). This method provides an effective reference for the direct use of plasmin for fibrinolytic therapy [75]. However, the fibrinolytic enzyme in the nanoparticles can be released to a high degree only when thrombin-triggered instability occurs.…”

Section: Liposome Drug Deliverymentioning

confidence: 99%

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery

Ren,

Mi,

Wei

et al. 2024

Molecules

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Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

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“…1,2 Its main advantage lies in its powerful ability to catalyze the conversion of brinogen to brin, and it is a key accelerator in the process of blood coagulation. 3,4 However, the major challenge is to maintain the delicate equilibrium between the dosage of thrombin and its safety. 5,6 High concentrations may result in excessive coagulation, leading to thrombosis and serious complications.…”

Section: Introductionmentioning

confidence: 99%

Sono-responsive smart nanoliposomes for precise and rapid hemostasis application

Zhang,

Zhu,

Wang

et al. 2024

RSC Adv.

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Direct delivery of plasmin using clot-anchoring thrombin-responsive nanoparticles for targeted fibrinolytic therapy

Cited by 8 publications

References 57 publications

pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis

pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery

Sono-responsive smart nanoliposomes for precise and rapid hemostasis application

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