Soodabeh Hassanpour1, Han-Jun Kim2,3, Arezoo Saadati4, Peyton Tebon2, Chengbin Xue2, Floor W van den Dolder2,5,6, Jai Thakor2, Behzad Baradaran7, Jafar Mosafer8, Amir Baghbanzadeh7, Natan Roberto de Barros2, Mahmoud Hashemzaei9, Kang Ju Lee2, Junmin Lee2, Shiming Zhang2, Wujin Sun2, Hyun-Jong Cho2,10, Samad Ahadian2,3, Nureddin Ashammakhi2,11, Mehmet R Dokmeci2,3,11, Ahad Mokhtarzadeh7,* Ali Khademhosseini2,3,11,12,*
1Department of Analytical Chemistry, Faculty of Science, Palacky University Olomouc, 17. Listopadu 12, Olomouc, 77146, Czech Republic.
2Department of Bioengineering, Center for Minimally Invasive Therapeutics (C-MIT) and California NanoSystems Institute University of California-Los Angeles, Los Angeles, CA, 90095, USA.
3Terasaki Institute for Biomedical Innovation, Los Angeles, CA, 90024, USA.
4Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, 516614731, Iran.
5Division Heart and Lungs, Department of Cardiothoracic Surgery, University Medical Center Utrecht, Utrecht, GA, 3508, The Netherlands.
6Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, CT, 3584, The Netherlands.
7Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, 516614731, Iran.
8Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, 9519633787, Iran.
9Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, 9861618335, Iran.
10College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341, Republic of Korea.
11Jonsson Comprehensive Cancer Center, Department of Radiology and Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, CA, 90095, USA.
12Department of Chemical and Biomolecular Engineering, Henry Samueli School of Engineering and Applied Sciences, University of California - Los Angeles, Los Angeles, CA, 90095, USA.
S.H. and H.‐J.K. contributed equally to this work.
Thrombosis is a life‐threatening pathological condition in which blood clots form in blood vessels, obstructing or interfering with blood flow. Thrombolytic agents (TAs) are enzymes that can catalyze the conversion of plasminogen to plasmin to dissolve blood clots. The plasmin formed by TAs breaks down fibrin clots into soluble fibrin that finally dissolves thrombi. Several TAs have been developed to treat various thromboembolic diseases, such as pulmonary embolisms, acute myocardial infarction, deep vein thrombosis, and extensive coronary emboli. However, systemic TA administration can trigger non‐specific activation that can increase the incidence of bleeding. Moreover, protein‐based TAs are rapidly inactivated upon injection resulting in the need for large doses. To overcome these limitations, various types of nanocarriers have been introduced that enhance the pharmacokinetic effects by protecting the TA from the biological environment and targeting the release into coagulation. The nanocarriers show increasing half‐life, reducing side effects, and improving overall TA efficacy. In this work, the recent advances in various types of TAs and nanocarriers are thoroughly reviewed. Various types of nanocarriers, including lipid‐based, polymer‐based, and metal‐based nanoparticles are described, for the targeted delivery of TAs. This work also provides insights into issues related to the future of TA development and successful clinical translation.