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

Resham Chaudhary, Kislay Roy, Rupinder K. Kanwar, Rakesh N. Veedu, Subramanian Krishnakumar, Chun-Hei Cheung, Anita K. Verma, Jagat R. Kanwar

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 1.0M Dox in the Ecad01-Dox conjugate was able to show similar cytotoxicity to 10M 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 30min, 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.

Original languageEnglish
Pages (from-to)1108-1116
Number of pages9
JournalAustralian Journal of Chemistry
Volume69
Issue number10
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Cadherins
Doxorubicin
Cells
Chitosan
Cytotoxicity
Ionotropic gelation
Nucleotide Aptamers
Chemical modification
Cell proliferation
Encapsulation
Assays
Tissue
Nanoparticles

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Chaudhary, R., Roy, K., Kanwar, R. K., Veedu, R. N., Krishnakumar, S., Cheung, C-H., ... Kanwar, J. R. (2016). E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells. Australian Journal of Chemistry, 69(10), 1108-1116. https://doi.org/10.1071/CH16211
Chaudhary, Resham ; Roy, Kislay ; Kanwar, Rupinder K. ; Veedu, Rakesh N. ; Krishnakumar, Subramanian ; Cheung, Chun-Hei ; Verma, Anita K. ; Kanwar, Jagat R. / E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells. In: Australian Journal of Chemistry. 2016 ; Vol. 69, No. 10. pp. 1108-1116.
@article{441c1ae574844786a6f6420cda6ff93b,
title = "E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells",
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 1.0M Dox in the Ecad01-Dox conjugate was able to show similar cytotoxicity to 10M 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 30min, 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.",
author = "Resham Chaudhary and Kislay Roy and Kanwar, {Rupinder K.} and Veedu, {Rakesh N.} and Subramanian Krishnakumar and Chun-Hei Cheung and Verma, {Anita K.} and Kanwar, {Jagat R.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1071/CH16211",
language = "English",
volume = "69",
pages = "1108--1116",
journal = "Australian Journal of Chemistry",
issn = "0004-9425",
publisher = "CSIRO",
number = "10",

}

Chaudhary, R, Roy, K, Kanwar, RK, Veedu, RN, Krishnakumar, S, Cheung, C-H, Verma, AK & Kanwar, JR 2016, 'E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells', Australian Journal of Chemistry, vol. 69, no. 10, pp. 1108-1116. https://doi.org/10.1071/CH16211

E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells. / Chaudhary, Resham; Roy, Kislay; Kanwar, Rupinder K.; Veedu, Rakesh N.; Krishnakumar, Subramanian; Cheung, Chun-Hei; Verma, Anita K.; Kanwar, Jagat R.

In: Australian Journal of Chemistry, Vol. 69, No. 10, 01.01.2016, p. 1108-1116.

Research output: Contribution to journalArticle

TY - JOUR

T1 - E-Cadherin Aptamer-Conjugated Delivery of Doxorubicin for Targeted Inhibition of Prostate Cancer Cells

AU - Chaudhary, Resham

AU - Roy, Kislay

AU - Kanwar, Rupinder K.

AU - Veedu, Rakesh N.

AU - Krishnakumar, Subramanian

AU - Cheung, Chun-Hei

AU - Verma, Anita K.

AU - Kanwar, Jagat R.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 1.0M Dox in the Ecad01-Dox conjugate was able to show similar cytotoxicity to 10M 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 30min, 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.

AB - 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 1.0M Dox in the Ecad01-Dox conjugate was able to show similar cytotoxicity to 10M 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 30min, 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.

UR - http://www.scopus.com/inward/record.url?scp=84990201777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990201777&partnerID=8YFLogxK

U2 - 10.1071/CH16211

DO - 10.1071/CH16211

M3 - Article

VL - 69

SP - 1108

EP - 1116

JO - Australian Journal of Chemistry

JF - Australian Journal of Chemistry

SN - 0004-9425

IS - 10

ER -