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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH FRONT

E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells

Resham Chaudhary A , Kislay Roy A , Rupinder K. Kanwar A , Rakesh N. Veedu B C , Subramanian Krishnakumar D E , Chun Hei Antonio Cheung F G , Anita K. Verma H and Jagat R. Kanwar A I
+ Author Affiliations
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A Nanomedicine Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, Vic. 3217, Australia.

B Centre for Comparative Genomics, Murdoch University, Perth, WA 6150, Australia.

C Western Australian Neuroscience Research Institute, Perth, WA 6150, Australia.

D Department of Nanobiotechnology, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, Tamil Nadu 600006, India.

E Larsen and Toubro Department of Opthalmology, Vision Research Foundation, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Chennai, Tamil Nadu 600006, India.

F Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

G Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

H Nanobiotech Laboratory, Department of Zoology, Kirorimal College, University of Delhi, Delhi 110007, India.

I Corresponding author. Email: jagat.kanwar@deakin.edu.au

Australian Journal of Chemistry 69(10) 1108-1116 https://doi.org/10.1071/CH16211
Submitted: 31 March 2016  Accepted: 20 July 2016   Published: 24 August 2016

Abstract

Regardless of the tremendous effort to develop an effective therapeutic approach to combat prostate cancer, target-specific therapy without adverse side effects on healthy tissues and cells is yet to be achieved. Triggered by this craving, we herein report the synthesis of algal chitosan nanoparticles containing DNA aptamer-targeting E-cadherin (Ecad01) using an ionotropic gelation method for target-specific delivery of doxorubicin (Dox) to inhibit prostate cancer cell (DU145) proliferation. The designed chimeric Ecad01-Dox conjugate exhibited excellent targeted internalization, which was evident from a 1.71-fold-increased internalization in DU145 cells, and showed significantly lower uptake (1.92-fold lower) in non-cancerous cells (RWPE-1). Moreover, cell viability assay results showed that 1.0 µM Dox in the Ecad01-Dox conjugate was able to show similar cytotoxicity to 10 µM Dox in DU145 cells, which is indicative of targeted cancer-specific inhibition. Our study clearly demonstrated that encapsulation of Ecad01-Dox conjugate in algal chitosan increased its cellular uptake to 58 % in 30 min, with reduced non-specific cytotoxicity and enhanced chemotherapeutic potential. This could be a simple and an effective targeted drug-delivery strategy that does not require chemical modification of the doxorubicin or the Ecad01 aptamer with potential in developing a therapeutic agent for prostate cancer.


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