Lethal drug combination: Arsenic loaded multiple drug mesoporous silica for theranostic applications

Abstract

Simultaneous delivery of multiple therapeutic agents is of great importance for effective chemotherapy due of its well-known drug synergism and suppression to chemoresistance. We report a new theranostic nanoformulation to shuttle multiple chemotherapeutic agents for successfully exterminating cancer cells. This strategy is based on the fabrication of magnetite doped mesoporous silica nanoparticles (MSNs) in which both internal porous and external surface of MSN are respectively exploited to load two different kinds of cytotoxic cargoes. Notably, an exceptionally high quantity (29%) of poorly hydrophobic drug camptothecin (CPT) is loaded into the nanopores of MSNs; however, in previous reports less than 1% loading efficiency is reported. Following CPT loading in the pores of MSNs, another unconventional but FDA approved arsenic trioxide (ATO) is conjugated onto the surface of nanocomposite via exploiting the thiophilic nature of ATO. Cell inhibition performance of dual drug nanoformulation is significantly higher than single drug formulation, possibly due to additional or synergistic effect, as low as 3μg/ml of double drug nanocarrier were found effective to exterminate cancer cells. Besides drug delivery, the presence of superparamagnetic magnetite nanocrystals additionally empowers this system to be used as a contrast agent in magnetic resonance (MR) imaging for either monitoring diseased tissues or feedback of chemotherapy. We anticipate that the integration of combination therapy with nanotechnology coupled with versatile magnetic manipulation feature may prove a significant step forward toward the development of effective theranostic agents.