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Issue 13, 2014
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Smart pH- and reduction-dual-responsive folate–PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

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Abstract

To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate–PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (∼50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand–receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications.

Graphical abstract: Smart pH- and reduction-dual-responsive folate–PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

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Supplementary files

Article information


Submitted
14 Feb 2014
Accepted
26 Apr 2014
First published
09 May 2014

Nanoscale, 2014,6, 7635-7642
Article type
Paper

Smart pH- and reduction-dual-responsive folate–PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

S. Wang, H. Wang, Z. Liu, L. Wang, X. Wang, L. Su and J. Chang, Nanoscale, 2014, 6, 7635 DOI: 10.1039/C4NR00843J

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