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The pH-dependent association with cancer cells of tunable functionalized lipid vesicles with encapsulated doxorubicin for high cell-kill selectivity

Paper ID Volume ID Publish Year Pages File Format Full-Text
8448 590 2010 8 PDF Available
Title
The pH-dependent association with cancer cells of tunable functionalized lipid vesicles with encapsulated doxorubicin for high cell-kill selectivity
Abstract

To enable selective cell-kill, we designed functionalized lipid vesicles with pH-triggered heterogeneous membranes and encapsulated doxorubicin that exhibit tunable surface topography. These vesicles “hide” (mask) the targeting ligands from their surface during circulation in the blood, and only progressively “expose” these ligands as they gradually penetrate deeper into the tumor interstitium, where after endocytosis they burst release their contents. The stimulus to activate the binding reactivity is the pH gradient between the blood stream (pH 7.4–7.0) and the increasingly acidic pH inside the tumor interstitium (pH 6.7–6.5). Doxorubicin release is activated at the endosomal pH 5.5–5.0. We show that tunable functionalized vesicles exhibit environmentally-dependent (pH-dependent) association with cancer cells resulting in high cell-kill selectivity. When lowering the extracellular pH from 7.4 to 6.5, tunable functionalized vesicles deliver doxorubicin to cancer cells that increases from 41% to 93% of maximum resulting in cancer cell killing that increases from 23 to 71% of maximum, respectively. This proof-of-concept shows the potential of tunable targeted liposomal chemotherapy to selectively kill cancer cells in an environmentally-dependent way.

Keywords
Liposomes; Chemotherapy; Targeted liposomal chemotherapy
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The pH-dependent association with cancer cells of tunable functionalized lipid vesicles with encapsulated doxorubicin for high cell-kill selectivity
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 15, May 2010, Pages 4409–4416
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