Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs

Abstract Co-delivery of hydrophilic siRNA and hydrophobic drugs is one of the major challenges for nanomaterial-based medicine. Here, we present a simple but multifunctional micellar platform constructed by a matrix metalloproteinase 2 (MMP2)-sensitive copolymer (PEG-pp-PEI-PE) via self-assembly for...

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Bibliographic Details
Published in:Biomaterials 2014-04, Vol.35 (13), p.4213-4222
Main Authors: Zhu, Lin, Perche, Federico, Wang, Tao, Torchilin, Vladimir P
Format: Article
Language:English
Subjects:
Advanced Basic Science
Cell Line, Tumor
Dentistry
Drug Delivery Systems - methods
Humans
Hydrophobic and Hydrophilic Interactions
Life Sciences
Matrix metalloproteinase
Matrix Metalloproteinase 2
Micelles
Phosphatidylethanolamines - chemistry
Polyethylene Glycols - chemistry
Polymeric micelles
Polymers - chemistry
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Self-assembly
siRNA and drug delivery
Stimulus-sensitive
Tumor targeting
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Summary:Abstract Co-delivery of hydrophilic siRNA and hydrophobic drugs is one of the major challenges for nanomaterial-based medicine. Here, we present a simple but multifunctional micellar platform constructed by a matrix metalloproteinase 2 (MMP2)-sensitive copolymer (PEG-pp-PEI-PE) via self-assembly for tumor-targeted siRNA and drug co-delivery. The micellar nanocarrier possesses several key features for siRNA and drug delivery, including (i) excellent stability; (ii) efficient siRNA condensation by PEI; (iii) hydrophobic drug solubilization in the lipid “core”; (iv) passive tumor targeting via the enhanced permeability and retention (EPR) effect; (v) tumor targeting triggered by the up-regulated tumoral MMP2; and (vi) enhanced cell internalization after MMP2-activated exposure of the previously hidden PEI. These cooperative functions ensure the improved tumor targetability, enhanced tumor cell internalization, and synergistic antitumor activity of co-loaded siRNA and drug.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2014.01.060