Self-Assembled Nanocomplex for Co-Delivery of Arsenic-Retinoic Acid Prodrug into Acute Promyelocytic Leukemia Cells

Journal of Biomedical Nanotechnology
Jing FanZhiming Cai

Abstract

The synergistic effect of arsenic (As) and all-trans retinoic acid in acute promyelocytic leukemia (APL) has been well documented. However, several major issues impeding the efficient delivery of these drugs for APL therapy remain unsolved. The low solubility of retinoic acid in physiological solutions makes drug delivery cumbersome, and the high systemic cytotoxicity of arsenic trioxide leads to unwanted side effects. In the present study, a new organo-arsenic molecule was synthesized via template-directed ring-opening esterification of an epoxy arsenic hydride (2-chloro-1,3,2-dioxaarsolane, CDA) under a nucleophilic attack exposing the hydroxyl terminus. The additional single step conjugation with retinoic acid (RA) and polyethylene glycol (PEG) yielded the amphiphilic prodrug PEG-As-RA that readily self-assembles into nanoparticles in the aqueous phase. The assembled nanoparticles containing both arsenic and RA exhibit high water solubility and good biocompatibility. In addition, they are highly stable in physiological buffers and are efficiently taken up by human APL cells. In vivo imaging results showed that the nanoparticles are characterized by prolonged blood circulation, and release both RA and As via hydrolysis to pro...Continue Reading

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