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Hb5 Aptamer-Tagged Graphene Oxide for Co-Delivery of Doxorubicin and Silibinin, and Highly Effective Combination Therapy in Breast Cancer Publisher



Shahidi M1 ; Haghiralsadat BF2 ; Abazari O1 ; Hemati M2, 3 ; Dayati P4 ; Jaliani HZ5 ; Motlagh NSH6 ; Naghib SM7 ; Moradi A1
Authors
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
  2. 2. Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  3. 3. Department of Clinical Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  4. 4. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  6. 6. Department of Biomedical Engineering, Meybod University, Meybod, Iran
  7. 7. Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology and Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, IUST, ACECR, Tehran, Iran

Source: Cancer Nanotechnology Published:2023


Abstract

Using a chemotherapeutic agent, such as doxorubicin (DOX), with a natural agent, such as silibinin (Sili), is highly valuable to minimize systemic toxicity. However, Sili and DOX face disadvantages, such as low aqueous solubility and poor bioavailability. Here, we have engineered a drug delivery cargo by decorating carboxylated graphene oxide (cGO) with an aptamer, HB5, for simultaneous delivery of DOX and Sili as a combination therapy against MCF-7 and SK-BR-3 breast cancer cells. The resulting Apt-cGO displayed a typical sheet-like nanostructure with a broad surface. The maximum entrapment efficiency was 70.42% and 84.22% for Sili and DOX, respectively. When the Apt-cGO-DOX-Sili nanocomposites were selectively taken up by breast cancer cells, the interaction between cGO and drugs was cleaved, causing releasing both Sili and DOX into the tumor cells, respectively. Compared to free drugs, Apt-cGO-DOX-Sili nanocomposites displayed higher cytotoxicity in vitro. Apt-cGO-DOX-Sili nanocomposites potentially suppressed some cancer cell survival signals. They accelerated cell apoptosis and increased Rb levels as well as reduced Akt, mTOR, NF-κB, and CDK2 levels. In conclusion, the developed Apt-cGO-DOX-Sili can be suggested as a simple and efficient drug delivery approach for breast chemotherapy. © 2023, The Author(s).
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