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Chemical Architecture of Block Copolymers Differentially Abrogate Cardiotoxicity and Maintain the Anticancer Efficacy of Doxorubicin by Chowdhury S. Abdullah; Priyanka Ray; Shafiul Alam; Narendra Kale; Richa Aishwarya; Mahboob Morshed; Debasmita Dutta; Cathleen Hudziak; Sushanta K. Banerjee; Sanku Mallik; Snigdha Banerjee; Md. Shenuarin Bhuiyan; Mohiuddin Quadir is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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The molecular architecture of pH-responsive amphiphilic block copolymers, their self-assembly behavior to form nanoparticles (NPs), and doxorubicin (DOX)-loading technique govern the extent of DOX-induced cardiotoxicity. We observed that the choice of pH-sensitive tertiary amines, surface charge, and DOX-loading techniques within the self-assembled NPs strongly influence the release and stimulation of DOX-induced cardiotoxicity in primary cardiomyocytes. However, covalent conjugation of DOX to a pH-sensitive nanocarrier through a "conditionally unstable amide" linkage (PCPY-cDOX; PC = polycarbonate and PY = 2-pyrrolidine-1-yl-ethyl-amine) significantly reduced the cardiotoxicity of DOX in cardiomyocytes as compared to noncovalently encapsulated DOX NPs (PCPY-eDOX). When these formulations were tested for drug release in serum-containing media, the PCPY-cDOX systems showed prolonged control over drug release (for ∼72 h) at acidic pH compared to DOX-encapsulated nanocarriers, as expected. We found that DOX-encapsulated nanoformulations triggered cardiotoxicity in primary cardiomyocytes more acutely, while conjugated systems such as PCPY-cDOX prevented cardiotoxicity by disabling the

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Author

Chowdhury S. Abdullah; Priyanka Ray; Shafiul Alam; Narendra Kale; Richa Aishwarya; Mahboob Morshed; Debasmita Dutta; Cathleen Hudziak; Sushanta K. Banerjee; Sanku Mallik; Snigdha Banerjee; Md. Shenuarin Bhuiyan; Mohiuddin Quadir

Publisher

American Chemical Society; American Chemical Society (ACS) (ISSN 1543-8384)

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)