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.
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.
Entities:
Keywords:
MMP-2; drug delivery system; gelatin; gelatin zymography; synergistic therapy
Authors: Gracjana Krzysiek-Maczka; Aneta Targosz; Tomasz Wrobel; Milena Paw; Urszula Szczyrk; Janusz Opila; Malgorzata Strzalka; Mateusz Wierdak; Piotr Major; Tomasz Brzozowski; Jarosław Czyz; Agata Ptak-Belowska Journal: Am J Cancer Res Date: 2022-03-15 Impact factor: 6.166
Authors: Biao Chen; Xiaoqi Dong; Xiyuan Dong; Quan Wang; Meng Wu; Jun Wu; Xiaoding Lou; Fan Xia; Wenwen Wang; Jun Dai; Shixuan Wang Journal: Int J Nanomedicine Date: 2021-02-18