title: 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 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.
authors: 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.
authors: Lin
authors: L
authors: Zhu
authors: Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States.
authors: Federico
authors: F
authors: Perche
authors: Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States.
authors: Tao
authors: T
authors: Wang
authors: Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, United States. Electronic address: v.torchilin@neu.edu.
authors: Vladimir P
authors: VP
authors: Torchilin
mesh_terms: D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D020778:Matrix Metalloproteinase 2; D008823:Micelles; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; D034741:RNA, Small Interfering; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols; D020778:Matrix Metalloproteinase 2
keywords: Matrix metalloproteinase; Polymeric micelles; Self-assembly; Stimulus-sensitive; Tumor targeting; siRNA and drug delivery