Journal
BIOMATERIALS
Volume 35, Issue 13, Pages 4213-4222Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.01.060
Keywords
Self-assembly; Polymeric micelles; Stimulus-sensitive; Matrix metalloproteinase; siRNA and drug delivery; Tumor targeting
Funding
- NIH [1R01CA121838, U54CA151881]
- American Cancer Society-Ellison Foundation [PF-13-361-01-CDD]
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Co-delivery of hydrophilic siRNA and hydrophobic drugs is one of the major challenges for nanomaterialbased 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. (C) 2014 Elsevier Ltd. All rights reserved.
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