A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots

Seo, Junyoung; Al-Hilal, Taslim A.; Jee, Jun Goo; Kim, Yong Lim; Kim, Ha Jeong; Lee, Byung Heon; Kim, Soyoun; Kim, In San

doi:10.1016/j.nano.2017.12.022

Cited by 23 publications

(23 citation statements)

References 38 publications

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“…McCarthy et al, has demonstrated that nanocomposites with a FXIIIa-sensitive peptide shows an enhanced binding to thrombus with a similar efficacy as free rtPA in vivo [30]. In addition, peptide targeting fibrin-fibrinogen complex may be used to deliver micro-plasmin that directly degrades fibrin [31].…”

Section: Targeting Strategymentioning

confidence: 99%

“…The speed and extend of thrombus formation greatly depend on concentration of FeCl 3 , how long the filter paper gets in contact with the vessels, the artery size and animal species. It has been demonstrated that different arteries, including carotid and middle cerebral arteries [15,23,26,31], can be occluded by FeCl 3 -induced thrombosis. However, endothelial damage-generated robust signals continuously trigger thrombus formation, which is quite difficult to use thrombolytic agent alone to restore blood flow in this model [26,42].…”

Section: Animal Models For Assessment Of Thrombolytic Nanocompositesmentioning

confidence: 99%

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Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation

Liu

Liang

et al. 2019

Molecules

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In thrombolytic therapy, plasminogen activators (PAs) are still the only group of drug approved to induce thrombolysis, and therefore, critical for treatment of arterial thromboembolism, such as stroke, in the acute phase. Functionalized nanocomposites have attracted great attention in achieving target thrombolysis due to favorable characteristics associated with the size, surface properties and targeting effects. Many PA-conjugated nanocomposites have been prepared and characterized, and some of them has been demonstrated with therapeutic efficacy in animal models. To facilitate future translation, this paper reviews recent progress of this area, especially focus on how to achieve reproducible thrombolysis efficacy in vivo.

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Section: Targeting Strategymentioning

confidence: 99%

Section: Animal Models For Assessment Of Thrombolytic Nanocompositesmentioning

confidence: 99%

Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation

Liu

Liang

et al. 2019

Molecules

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“…The recombinant plasmids for the expression of the TRAIL Active Trimer NanoCage (ATNC) were constructed as described previously 79 . The TRAIL (114–281) gene was incorporated between NdeI and BamHI in pET-28a plasmid (69864-3, Novagen, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Designed ferritin nanocages displaying trimeric TRAIL and tumor-targeting peptides confer superior anti-tumor efficacy

Yoo

Bae²,

Seo

et al. 2020

Sci Rep

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TRAIL is considered a promising target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors, DR4 or DR5. Although recombinant human TRAIL has shown high potency and specificity for killing cancer cells in preclinical studies, it has failed in multiple clinical trials for several reasons, including a very short half-life mainly caused by instability of the monomeric form of TRAIL and rapid renal clearance of the off-targeted TRAIL. To overcome such obstacles, we developed a TRAIL-active trimer nanocage (TRAIL-ATNC) that presents the TRAIL ligand in its trimer-like conformation by connecting it to a triple helix sequence that links to the threefold axis of the ferritin nanocage. We also ligated the tumor-targeting peptide, IL4rP, to TRAIL-ATNC to enhance tumor targeting. The developed TRAIL-ATNCIL4rP showed enhanced agonistic activity compared with monomeric TRAIL. The in vivo serum half-life of TRAIL-ATNCIL4rP was ~ 16-times longer than that of native TRAIL. As a consequence of these properties, TRAIL-ATNCIL4rP exhibited efficacy as an anti-tumor agent in vivo against xenograft breast cancer as well as orthotopic pancreatic cancer models, highlighting the promise of this system for development as novel therapeutics against cancer.

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“…Ferritin can be applied for drug loading by disassembly and reassembly procedures through changes of pH [101][102][103]. In 2018, Seo et al [104] engineered a subunit of short ferritin with blood-clot-targeting peptides (CLT) on its N-terminal and the thrombolytic microplasmin (μPg) on its C-terminal. The CLT on the ferritin could target fibrin-fibronectin complexes, providing a thrombus-targeting property to the engineered ferritin.…”

Section: Biological Nanostructure-based Drug Deliverymentioning

confidence: 99%

Nano-Medicine for Thrombosis: A Precise Diagnosis and Treatment Strategy

Dai

Chen³

et al. 2020

Nano-Micro Lett.

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HIGHLIGHTS • Recent advances in diagnosis and treatment of thrombosis using nano-medicine are summarized in this review. • The diagnosis system based on biomarkers and imaging nanoprobes could enable the detection in early state of thrombosis. • The targeted drug delivery nanosystems serve as clinically translatable theranostics for thrombosis treatment with minor side effects. ABSTRACT Thrombosis is a global health issue and one of the leading factors of death. However, its diagnosis has been limited to the late stages, and its therapeutic window is too narrow to provide reasonable and effective treatment. In addition, clinical thrombolytics suffer from a short half-life, allergic reactions, inactivation, and unwanted tissue hemorrhage. Nano-medicines have gained extensive attention in diagnosis, drug delivery, and photo/sound/magnetic-theranostics due to their convertible properties. Furthermore, diagnosis and treatment of thrombosis using nano-medicines have also been widely studied. This review summarizes the recent advances in this area, which revealed six types of nanoparticle approaches: (1) in vitro diagnostic kits using "synthetic biomarkers"; (2) in vivo imaging using nano-contrast agents; (3) targeted drug delivery systems using artificial nanoparticles; (4) microenvironment responsive drug delivery systems; (5) drug delivery systems using biological nanostructures; and (6) treatments with external irradiation. The investigations of nano-medicines are believed to be of great significance, and some of the advanced drug delivery systems show potential applications in clinical theranotics.

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A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots

Cited by 23 publications

References 38 publications

Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation

Targeted Delivery of Plasminogen Activators for Thrombolytic Therapy: An Integrative Evaluation

Designed ferritin nanocages displaying trimeric TRAIL and tumor-targeting peptides confer superior anti-tumor efficacy

Nano-Medicine for Thrombosis: A Precise Diagnosis and Treatment Strategy

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