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Gold-Capped Mesoporous Silica Nanoparticles As an Excellent Enzyme-Responsive Nanocarrier for Controlled Doxorubicin Delivery Publisher Pubmed



Eskandari P1 ; Bigdeli B1 ; Porgham Daryasari M2 ; Baharifar H3 ; Bazri B4 ; Shourian M5 ; Amani A3 ; Sadighi A6 ; Goliaei B1 ; Khoobi M2, 7 ; Saboury AA1
Authors
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Authors Affiliations
  1. 1. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  2. 2. Biomaterials Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Chemistry, Amirkabir University of Technology, Tehran, Iran
  5. 5. Department of Biology, University of Guilan, Rasht, Iran
  6. 6. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, United States
  7. 7. Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center (MBRC), Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Drug Targeting Published:2019


Abstract

Mesoporous silica nanoparticles (MSNs) have ideal characteristics as next generation of controlled drug delivery systems. In this study, a MSN-based nanocarrier was fabricated and gold nanoparticle (GNP)-biotin conjugates were successfully grafted onto the pore outlets of the prepared MSN. This bioconjugate served as a capping agent with a peptide-cleavable linker sensitive to matrix metalloproteinases (MMPs), which are overexpressed extracellular proteolytic enzymes in cancerous tissue. The prepared nanocarriers were fully characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption, Fourier transform infra-red spectroscopy (FTIR), dynamic light scattering (DLS) and thermo gravimetric analysis (TGA). In vitro release studies showed efficient capping of MSNs with gold gate and controlled release of Doxorubicin (DOX) in the presence of matrix metalloproteinase-2 (MMP-2) and acidic pH values. High DOX-loading capacity (21%) and encapsulation efficiency (95.5%) were achieved using fluorescence technique. DOX-loaded nanocarriers showed high cytocompatibility and could efficiently induce cell death and apoptosis in the MMP-2 overexpressed cell lines. Moreover, Haemolysis, platelet activation and inflammatory responses assessment approved excellent hemocompatibility and minimal side effects by encapsulation of DOX in MSNs carrier. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.