Anti-Mucin1 Aptamer-Conjugated Chitosan Nanoparticles for Targeted Co-Delivery of Docetaxel and IGF-1R siRNA to SKBR3 Metastatic Breast Cancer Cells

Authors
Reza Jafari 1
Naime Majidi Zolbanin 2
Jafar Majidi 3
Fatemeh Atyabi 4
Mehdi Yousefi 5
Farhad Jadidi-Niaragh 5
Leili Aghebati-Maleki 3
Dariush Shanehbandi 3
Mohammad-Sadegh Soltani Zangbar 5
Houshang Rafatpanah 6
1 Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;
2 Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6 Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran
10.29252/ibj.23.1.21
Abstract
Background: Targeted co-delivery of siRNA and a chemotherapeutic drug is an attractive approach to cancer drug design and treatment. This study was carried out to design an anti-Mucin1 aptamer (Apt)-conjugated chitosan nanoparticle (NP) for targeted co-delivery of insulin-like growth factor receptor 1 (IGF-1R) Silencer siRNA and docetaxel (DTX) to SKBR3 cells. Methods: Characterization of nano-drugs, cellular uptake of NPs, cell viability, and gene expression studies were evaluated based on metastatic breast cancer cells. Results: The results of this study showed that NPs had spherical and smooth morphology with 110-118 nm in size and had positive zeta potential (12-14 mV). siRNA and DTX were considerably loaded into NPs. The appropriate conjugation of the Apt to the NPs was affirmed by gel electrophoresis. The Apt-conjugated NPs were observed to enhance the cellular uptake of NPs into the SKBR3 cells. Although the combination treatment significantly decreased the cell viability of SKBR3 cells, the augmentative effect was observed when Apt was conjugated to NPs. Furthermore, Apt-conjugated NPs dramatically reduced the genetic expression of IGF-1R, signal transducers and activators of transcription 3 (STAT3), matrix metalloproteinases (MMP9), and vascular growth factor (VEGF). Conclusion: The targeted NPs may augment the targeting of pathways involved in tumorigenesis and metastasis of breast cancer. Therefore, more animal model experiments are needed to further clarify the efficacy and safety of this functionalized nanodrug.
Keywords
Breast cancer therapy
chitosan nanoparticles
Docetaxel
IGF-1R siRNA
MUC1 aptamer