MMP-2-responsive gelatin nanoparticles for synergistic tumor therapy.

ABSTRACT

Purpose: The aim of this study was to develop a new type of nanoparticle that enables concentrated drug release and synergistic therapy. Methods: To this end, we synthesized Ge-DOX-5-ALA/NPs, which can enter tumor tissue by the enhanced permeability and retention (EPR) effect and release drugs by utilizing matrix metalloproteinase-2 (MMP-2). Results: The Ge-DOX-5-ALA/NPs were synthesized by a single-phase coacervation method, and the hydrodynamic diameters of all nanoparticles were under 200 nm. The drug encapsulation and loading efficiency were 92%±1.13% and 6.02% ± 0.48%, respectively. Gelatin zymography was performed to detect the expression of MMP-2 in MCF-7 and Hs578Bst cells. The nanoparticle sensitivity to MMP-2 was examined by comparing the release behavior and cellular uptake in MCF-7 and Hs578Bst cells. In vitro cytotoxicity of the nanoparticles was measured by an MTT assay. An in vivo anticancer efficacy study in S180-bearing mice demonstrated that Ge-DOX-5-ALA/NPs provide a substantial curative effect. A pharmacokinetics experiment demonstrated that the nanoparticles have a sustained release effect. Conclusions: The MMP-2-triggered nanoparticles can transport drugs successfully into the tumor site and enable combined chemotherapy and photodynamic therapy.