Development of colloidal rare earth arsenites as arsenic trioxide nanoparticle prodrug (ATONP) for chemotherapy on a patient-derived xenograft model of colorectal cancer

Colloidal gadolinium arsenite has been developed as arsenic trioxide nanoparticle prodrug (ATONP) by our group in the past five years, and it has illustrated highly promising for cancer therapy. Here we systemically synthesize all the rare earth arsenites, characterize their element-dependant physico-chemical properties (composition, morphology, structure, colloidal charge and acidity), investigate their ATO releasing behavior as well as cytotoxicity applied them for chemotherapy of patient-derived xenograft model of colorectal cancer. All rare earth elements except cerium (Ce) arsenite colloids have similar structure, surface charge and stoichemistry ratio between rare earth and arsenic (1:0.9-1.2) and two dominant morphologies were found. As the prodrug of arsenic trioxide they showed similar ATO releasing kinetic against plasma, and close cytotoxicity on SMMC-7721 liver cancer cell line. Two representative colloidal prodrugs (lanthanide and gadolinium arsenates colloids) were applied on the chemotherapy of a patient-derived colorectal cancer xenograft model, and both ATO produgs have significantly better therapeutic effect than ATO, additionally they are highly tolerable and showed no significant toxicity. On the other hand, since several rare earth ions were probe sensitizer (Eu, Tb for luminescent, Gd for MRI) our result supply a serial of functional agents for image-guided chemotherapy.