AS1411 Aptamer Conjugated Gold Nanoclusters as a Targeted Radiosensitizer for Megavoltage Radiation Therapy of 4T1 Breast Cancer Cells

Document Type : Conference Proceedings

Authors

1 Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran. Bahare.ghahremani@gmail.com

2 Department of Oncology, Seyed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran, ahkefayat@yahoo.com

3 Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran. shahbazi@med.mui.ac.ir

Abstract

Introduction: In the present study, AS1411 aptamer conjugated gold nanoclusters (GNCs) have been introduced as a targeted radiosensitizer for enhancing megavoltage radiation therapy efficacy. RT has identified as an effective therapeutic modality for many different types of solid tumors. However, equal radiation beams absorption by tumor and surrounding healthy tissues is still a great challenge in RT which is caused by attenuation coefficient factor similarity. In order to overcome this challenge and to increase the efficacy of radiation therapy, radiosensitizers has been recommended.
 
Materials and Methods: GNCs with ultra-small gold core and bovine serum albumin shell (BSA) as a versatile Nano-platform were synthesized and conjugated to AS1411 aptamer (Apt-GNCs). Due to nucleolin overexpression in breast cancer cells and high affinity of the AS1411 aptamer to nucleolin, mouse mammary carcinoma cell line (4T1) was selected as malignant cells and murine fibroblast (L929) was used as a normal cell line.
 
Results: Flow cytometry assessments reveal a significant increase of GNCs uptake by the cancer cells in the presence of the aptamer as the targeting agent. Inductively coupled plasma optical emission spectrometry (ICP-OES) measurements demonstrate 4 times more Apt-GNCs uptake by 4T1 cells than the normal cells at concentration ratio of 1:40 (4µM Aptamer and 160 µM GNCs at 24h incubation).
Conclusion: Combination of megavoltage radiation therapy and Apt-GNCs as radiosensitizer causes effective cancer cells killing and obtaining dose enhancement factor (DEF) about 2.7 in clonogenic survival assay.

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History

  • Receive Date: 21 May 2018
  • Revise Date: 13 May 2019
  • Accept Date: 06 July 2018

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