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 provide combination therapy for human APL. This novel organo-arsenic molecule conjugated with RA offers a new approach to the treatment of APL.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.