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

Lin Zhu (1) , Federico Perche (1) , Tao Wang (1) , Vladimir Torchilin (1)

1 Northeastern University [Boston]

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.

Mots clés: Matrix metalloproteinase; Polymeric micelles; Self-assembly; Stimulus-sensitive; Tumor targeting; siRNA and drug delivery

Domaines: Sciences du Vivant [q-bio]

Lin Zhu, Federico Perche, Tao Wang, Vladimir Torchilin. Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs. Biomaterials, 2014, 35 (13), pp.4213-4222. ⟨10.1016/j.biomaterials.2014.01.060⟩. ⟨hal-02130742⟩