Controllable Thrombolysis Using a Nanobubble-Imaging-Guided rtPA Targeted Delivery Strategy

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Objective: The objective of this work is to design and fabricate a novel multifunctional nanocarrier combining thrombus-targeted imaging and ultrasound-mediated drug delivery for the theranostics of thrombotic diseases. Impact Statement: This study develops a new technology that can accurately visualize the thrombus and deliver drugs with controllable properties to diagnose and treat thrombotic diseases. Introduction: Thrombotic diseases are a serious threat to human life and health. The diagnosis and treatment of thrombotic diseases have always been a challenge. In recent years, nanomedicine has brought new ideas and new methods for the theranostics of thrombotic diseases. However, there are also many problems need to be solved, such as biosafety and stability of nanocarriers, early diagnosis, and timely treatment of thrombotic diseases, difficulty in clinical translation. Methods: The S1P@CD-PLGA-rtPA nanobubbles (NBs) were prepared by integrating sulfur hexafluoride (SF ₆)-loaded poly (D, L-lactide-co-glycolide) (PLGA) NBs, cyclodextrin (CD), sphingosine-1-phosphate (S1P), and recombinant tissue plasminogen activator (rtPA). Results: S1P@CD-PLGA-rtPA NBs had rapid and excellent thrombosis targeting imaging performance based on the specific interaction of S1P–S1PR1 (sphingosine-1-phosphate receptor 1). Furthermore, S1P@CD-PLGA-rtPA NBs that specifically targeting to the thrombosis regions could also respond to external ultrasound to achieve accurate and efficient delivery of rtPA to enhance the thrombolysis effectiveness and efficiency. Conclusion: This study proposes a new idea and strategy of targeting thrombus in rats via the specific interaction of S1P–S1PR1. On this basis, the acoustic response properties of bubble carriers could be fully utilized by combining thrombus-specific targeted imaging and ultrasound-mediated drug delivery for effective thrombolysis, which is expected to be applied in targeted diagnosis and treatment of thrombotic diseases in the future.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

Global Burden of Thrombosis: Table.

Gary Raskob, Aaron M. Wendelboe (2016)

Thromboembolic conditions were estimated to account for 1 in 4 deaths worldwide in 2010 and are the leading cause of mortality. Thromboembolic conditions are divided into arterial and venous thrombotic conditions. Ischemic heart disease and ischemic stroke comprise the major arterial thromboses and deep-vein thrombosis and pulmonary embolism comprise venous thromboembolism. Atrial fibrillation is a major risk factor for stroke and systemic arterial thromboembolism. Estimates of the global burden of disease were obtained from Global Burden of Disease Project reports, recent systematic reviews, and searching the published literature for recent studies reporting measures of incidence, burden, and disability-adjusted life-years. Estimates per 100 000 of the global incidence rate (IR) for each condition are ischemic heart disease, IR=1518.7; myocardial infarction, IR=139.3; ischemic stroke, IR=114.3; atrial fibrillation, IR=77.5 in males and 59.5 in females; and venous thromboembolism, IR=115 to 269. Mortality rates (MRs) for each condition are ischemic heart disease, MR=105.5; ischemic stroke, MR=42.3; atrial fibrillation, MR=1.7; and venous thromboembolism, MR=9.4 to 32.3. Global public awareness is substantially lower for pulmonary embolism (54%) and deep-vein thrombosis (44%) than heart attack (88%) and stroke (85%). Over time, the incidence and MRs of these conditions have improved in developed countries, but are increasing in developing countries. Public health efforts to measure disease burden and increase awareness of symptoms and risk factors need to improve, particularly in low- and middle-income regions to address this leading cause of morbidity and mortality.

0 comments Cited 311 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Deep vein thrombosis and pulmonary embolism

Marcello Di Nisio, Nick van Es, Harry Büller (2016)

Deep vein thrombosis and pulmonary embolism, collectively referred to as venous thromboembolism, constitute a major global burden of disease. The diagnostic work-up of suspected deep vein thrombosis or pulmonary embolism includes the sequential application of a clinical decision rule and D-dimer testing. Imaging and anticoagulation can be safely withheld in patients who are unlikely to have venous thromboembolism and have a normal D-dimer. All other patients should undergo ultrasonography in case of suspected deep vein thrombosis and CT in case of suspected pulmonary embolism. Direct oral anticoagulants are first-line treatment options for venous thromboembolism because they are associated with a lower risk of bleeding than vitamin K antagonists and are easier to use. Use of thrombolysis should be limited to pulmonary embolism associated with haemodynamic instability. Anticoagulant treatment should be continued for at least 3 months to prevent early recurrences. When venous thromboembolism is unprovoked or secondary to persistent risk factors, extended treatment beyond this period should be considered when the risk of recurrence outweighs the risk of major bleeding.

0 comments Cited 271 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Overview of therapeutic ultrasound applications and safety considerations.

Douglas Miller, Nadine Smith, Michael Bailey … (2012)

Applications of ultrasound in medicine for therapeutic purposes have been accepted and beneficial uses of ultrasonic biological effects for many years. Low-power ultrasound of about 1 MHz has been widely applied since the 1950s for physical therapy in conditions such as tendinitis and bursitis. In the 1980s, high-pressure-amplitude shock waves came into use for mechanically resolving kidney stones, and "lithotripsy" rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur, including burns from thermal-based therapies and severe hemorrhage from mechanical-based therapies (eg, lithotripsy). In all of these therapeutic applications of ultrasound bioeffects, standardization, ultrasound dosimetry, benefits assurance, and side-effect risk minimization must be carefully considered to ensure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks and therefore presents a manageable safety problem to the clinician. However, safety information can be scattered, confusing, or subject to commercial conflicts of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the American Institute of Ultrasound in Medicine, to the medical ultrasound community. In this overview, the Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.

0 comments Cited 162 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): BME Front

Journal ID (iso-abbrev): BME Front

Journal ID (publisher-id): BMEF

Title: BME Frontiers

Publisher: AAAS

ISSN (Electronic): 2765-8031

Publication date (Electronic, pub): 26 March 2024

Publication date (Electronic, collection): 2024

Volume: 5

Electronic Location Identifier: 0040

Affiliations

[1]State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University , Nanjing 210096, China.

Author notes

[*] [* ]Address correspondence to: yangfang2080@ 123456seu.edu.cn

Author information

Fang Yang https://orcid.org/0000-0001-6922-6348

Article

Publisher ID: 0040

DOI: 10.34133/bmef.0040

PMC ID: 10976949

PubMed ID: 38550853

SO-VID: a49d8a49-4742-4a75-816e-0c9d83af4396

License:

Exclusive licensee Suzhou Institute of Biomedical Engineering and Technology, CAS. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0).

History

Date received : 09 September 2023

Date accepted : 03 March 2024

Date: 26 March 2024

Page count

Figures: 6, Tables: 0, References: 38, Pages: 0

Funding

Funded by: National Key Research and Development Program of China, FundRef http://dx.doi.org/10.13039/501100012166;

Award ID: 2023YFF0713605, 2018YFA0704103

Award Recipient : Fang Yang

Funded by: Natural Science Foundation of Jiangsu Province, FundRef http://dx.doi.org/10.13039/501100004608;

Award ID: BK20222002

Award Recipient : Fang Yang

Funded by: National Natural Science Foundation of China, FundRef http://dx.doi.org/10.13039/501100001809;

Award ID: 81971750

Award Recipient : Fang Yang

Funded by: “333 Project” of Jiangsu Province, FundRef http://dx.doi.org/10.13039/501100018592;

Award ID: Project 333 of Jiangsu Province

Award Recipient : Fang Yang

Controllable Thrombolysis Using a Nanobubble-Imaging-Guided rtPA Targeted Delivery Strategy

Read this article at

Abstract

Related collections

RNA drug delivery

Most cited references 37

Global Burden of Thrombosis: Table.

Deep vein thrombosis and pulmonary embolism

Overview of therapeutic ultrasound applications and safety considerations.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 176

Most referenced authors 572