Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs
- Biomaterials. 2014 Apr;35(13):4213-22. doi: 10.1016/j.biomaterials.2014.01.060.
- 1. Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States; Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX 78363, United States.
- 2. Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States.
- 3. Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States. Electronic address: [email protected].
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.