Assessing the Combinatorial Chemo-Photothermal Therapy Mediated by Sulfobetaine Methacrylate-Functionalized Nanoparticles in 2D and 3D In Vitro Cancer Models.

Combinatorial cancer therapies mediated by nanomaterials can potentially overcome the limitations of conventional treatments. These therapies are generally investigated using 2D in vitro cancer models, leading to an inaccurate screening. Recently, 3D in vitro spheroids have emerged in the preclinical testing stage of nanomedicines due to their ability to mimic key features of the in vivo solid tumors. Investigate the chemo-photothermal therapy mediated by Doxorubicin and IR780 loaded sulfobetaine methacrylate functionalized nanoparticles, for the first time, using monolayers of cancer cells and spheroids. In the 2D cancer models, the nanomaterials' mediated photothermal therapy, chemotherapy, and chemo-photothermal therapy reduced cancer cells' viability to about 58%, 29%, and 1%, respectively. Interestingly, when the nanomaterials' mediated photothermal therapy is tested on 3D spheroids, no cytotoxic effect is noticed. In contrast, the nanostructures' induced chemotherapy decreased spheroids' viability to 42%. On the other hand, nanomaterials' mediated chemo-photothermal therapy diminished spheroids' viability to 16%, being the most promising therapeutic modality. These results demonstrate the importance of using 3D spheroids during the in vitro screening of single/combinatorial therapies mediated by nanomaterials.