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 1.0 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