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Fibrin degradation by rtPA enhances the delivery of nanotherapeutics to A549 tumors in nude mice

Paper ID Volume ID Publish Year Pages File Format Full-Text
5412 375 2016 9 PDF Available
Title
Fibrin degradation by rtPA enhances the delivery of nanotherapeutics to A549 tumors in nude mice
Abstract

Effective drug delivery to a tumor depends on favorable blood perfusion within the tumor. As an important component of tumor extracellular matrix, fibrin is abundant near tumor vessels. Inspired by the distinct distribution pattern and vessel-dependent production of fibrin, we hypothesized that fibrin depletion in tumors decompresses tumor vessels to improve tumor blood perfusion and accordingly enhance drug delivery to tumors rich in vessels. In the present study, we attempted to employ a clinically used thrombolytic drug, recombinant tissue plasminogen activator (rtPA), to modulate fibrin deposition in tumors. We then combined this drug with a nanoparticle drug delivery system for tumor therapy. RtPA treatment (25 mg/kg/d i. p. administration for two weeks) successfully depleted fibrin deposition and enhanced blood perfusion within A549 tumor xenografts. Furthermore, rtPA treatment also improved the in vivo delivery of 115-nm nanoparticles to tumor tissues. Finally, rtPA combined with therapeutic agent-loaded nanoparticles resulted in the most effective shrinkage of A549 tumor xenografts compared with the control groups. Overall, the present study provides a new strategy to enhance the delivery of nanotherapeutics to tumors rich in vessels.

Keywords
rtPA; Fibrin; Tumor therapy; Nanoparticle; Tumor vessels
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Fibrin degradation by rtPA enhances the delivery of nanotherapeutics to A549 tumors in nude mice
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 96, July 2016, Pages 63–71
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us