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Encapsulation and Delivery of an Osteosarcoma Stem Cell Active Gallium(III)-Diflunisal Complex Using Polymeric
Ginevra Passeri1, Ruby A Vincent1, Zhiyin Xiao1,2
1School of Chemistry, University of Leicester, LE1 7RH, Leicester, UK.
Abstract:
Here we report the encapsulation of an osteosarcoma stem cell (OSC) potent gallium(III)-diflunisal complex 1 into polymeric nanoparticles, and its delivery into osteosarcoma cells. At the optimum feed (20 %, 1 NP20 ), nanoparticle encapsulation of 1 enhances potency towards bulk osteosarcoma cells and OSCs (cultured in monolayer and three-dimensional systems). Strikingly, the nanoparticle formulation exhibits up to 5645-fold greater potency towards OSCs than frontline anti-osteosarcoma drugs, doxorubicin and cisplatin. The nanoparticle formulation evokes a similar mechanism of action as the payload, which bodes well for future translation. Specifically, the nanoparticle formulation induces nuclear DNA damage, cyclooxygenase-2 downregulation, and caspase-dependent apoptosis. To the best of our knowledge, this is the first study to demonstrate that polymeric nanoparticles can be used to effectively deliver an OSC-active metal complex into osteosarcoma cells.
