Arsenic compounds have been employed as therapeutics for centuries as treatments for diseases such as psoriasis, syphilis, rheumatosis and more recently leukaemia. Arsenic can exist in a number of oxidation states including biologically relevant As(V) and As(III), with As(III) exhibiting high cytotoxicity. In the 1980's arsenic trioxide (As2O3) was found to induced complete remission in suffers of acute promyelocytic leukaemia (APL) and has since been expolited to selectively target the adenine nucleotide translocator (ANT) in the mitochondrial membrance of proliferating cells (e.g. tumours) by altering the porosity of the mitchondrial membrane leading to apoptosis. Consequently, a number of small molecule (in)organic arsenicals have been developed and investigated to establish their therapeutic efficacy. On the macromolecular scale, research has focused on the development of arsenolipids which have been assembled into arsenoliposomes for encapsulation and targeted drug delivery applications against a variety of cancer cell lines. However, little is known about the efficacy of polymeric arsenicals either in the guise of protein/peptide-polymer conjugates or polymer nanoparticle therapeutics.  Herein we discuss the synthesis of novel arsenical initiators and monomers and the subsequent applictaion to the the synthesis of a library of polymeric arsenicals, via controlled radical polymerisation. Present as either As(V) or As(III), varying degrees of arsenic has been incorporated into the polymer composition. The resulting polymers have been screened against both healthy and cancerous cells to assess their cytotoxicity and therapeutic potential.

Therapeutic potential of polymeric arsenicals

248th National Meeting (2014)

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