Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels-Reference-Cited by-同舟云学术

Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels

Published:2012-08-10 Issue:6095 Volume:337 Page:738-742
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Korin Netanel¹,Kanapathipillai Mathumai¹,Matthews Benjamin D.²³,Crescente Marilena⁴⁵,Brill Alexander⁴⁵,Mammoto Tadanori²,Ghosh Kaustabh²,Jurek Samuel²,Bencherif Sidi A.¹⁶,Bhatta Deen⁶,Coskun Ahmet U.⁷,Feldman Charles L.⁸,Wagner Denisa D.⁴⁵,Ingber Donald E.¹²⁶

Affiliation:

1. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.

2. Vascular Biology Program, Departments of Pathology and Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

3. Department of Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

4. Immune Disease Institute, Program in Cellular and Molecular Medicine, Children’s Hospital Boston, Boston, MA 02115, USA.

5. Department of Pediatrics, Harvard Medical School, Harvard University, Boston, MA 02115, USA.

6. School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.

7. Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115, USA.

8. Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA.

Abstract

Bio-Inspired Drug Delivery Noting that platelets naturally migrate to narrowed blood vessels characterized by high fluid shear stress, Korin et al. (p. 738 , published online 5 July; see the Perspective by

Lavik and Ustin

) developed a nanoparticle-based therapeutic that uses a similar targeting mechanism to deliver a drug to vessels obstructed by blood clots. Aggregates of nanoparticles coated with the clot-dissolving drug tPA (tissue plasminogen activator) were designed to fall apart and release the drug only when encountering high fluid shear stress. In preclinical models, the bio-inspired therapeutic dissolved clots and restored normal blood flow at lower doses than free tPA, suggesting that this localized delivery system may help reduce the risk of side effects such as excessive bleeding.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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