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Anti Her-2 Aptamer Functionalized Gold Nanoparticles of Dasatinib for Targeted Chemo-Radiotherapy in Breast Cancer Cells Publisher Pubmed



Khorshid M1 ; Varshosaz J1 ; Rostami M2 ; Haghiralsadat F3 ; Akbari V4 ; Khorshid P5
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Advanced Medical Sciences, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  4. 4. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Source: Biomaterials Advances Published:2023


Abstract

In the present study, gold nanoparticles functionalized with anti HER-2 aptamer were designed for effective targeted delivery of dasatinib (DSB) to breast cancer cells. Anti HER-2 aptamer attached to porous or plain gold nanoparticles were compared for dasatinib delivery. Activated drug with succinic anhydride and L-cysteine linker was used for conjugation of DSB to gold nanoparticles. The loading efficiency of the activated drug on plain and porous gold nanoparticles was 52 and 68 %, respectively, which was significantly more than the loading of free DSB in gold nanoparticles (1–2.5 %). The anti HER-2 aptamer was conjugated to porous gold nanoparticles loaded with the activated drug. Various characterization techniques such as FESEM, TEM, AFM, zeta potential and ICP-MS were used to confirm the binding of the drug to gold nanoparticles. 1HNMR and FTIR spectroscopic analyses were employed to examine the structural characteristics of the conjugated drug. These analytical techniques confirmed the successful incorporation of succinyl and thiol groups onto the drug molecule. The amount of aptamer binding to different types of gold nanoparticles was obtained from the intensity of the light emitted from the bands observed in electrophoresis gel and due to the presence of porosity in porous gold nanoparticles, the amount of aptamer conjugation on porous gold nanoparticles increased compared to plain ones. Cell cytotoxicity and cellular uptake were evaluated by MTT assay and TEM in BT-474 and MCF-7 cells. Aptamer-functionalized porous gold nanoparticles containing activated dasatinib showed higher cytotoxicity and cellular uptake than modified DSB-loaded nanoparticles and un-activated DSB. The combination of radiation therapy with the modified dasatinib attached to porous gold nanoparticles and aptamer demonstrated a notable reduction in the IC50 values for both the BT-474 and MCF-7 cell lines. Specifically, the IC50 value for the BT-474 cells decreased from 6.95 μM (for unmodified dasatinib) to 2.57 μM, while for the MCF-7 cells, it decreased from 13.97 μM to 8.57 μM. These findings indicate a significant improvement in the efficacy of the modified dasatinib compared to its unmodified counterpart when used in conjunction with radiation therapy. © 2023 Elsevier B.V.
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