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Assessing the Combinatorial Chemo-Photothermal Therapy Mediated by Sulfobetaine Methacrylate-Functionalized
Inês Mó1, Cátia G Alves1, Duarte de Melo-Diogo1
1CICS-UBI - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Covilhã, 6200-506, Portugal.
Abstract:
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.
Insights
3D spheroids, not 2D models, accurately screen nanomaterial-based cancer therapies. Chemo-photothermal therapy using Doxorubicin and IR780 nanoparticles showed significant promise in 3D spheroid models.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Cancer Research
Background:
- Conventional 2D cancer models offer limited accuracy for nanomedicine screening.
- 3D spheroids better mimic in vivo solid tumor characteristics, crucial for preclinical nanomedicine testing.
Purpose of the Study:
- To evaluate chemo-photothermal therapy efficacy using Doxorubicin and IR780 loaded nanoparticles.
- To compare therapeutic outcomes in 2D cancer cell monolayers versus 3D spheroids.
Main Methods:
- Synthesized and characterized Doxorubicin and IR780 loaded sulfobetaine methacrylate functionalized nanoparticles.
- Tested nanoparticle efficacy in both 2D cancer cell cultures and 3D spheroids.
- Assessed viability after photothermal therapy, chemotherapy, and combined chemo-photothermal therapy.
Main Results:
- In 2D models, chemo-photothermal therapy achieved 1% viability; photothermal therapy reduced viability by 58%; chemotherapy by 29%.
- In 3D spheroids, photothermal therapy showed no cytotoxic effect; chemotherapy reduced viability to 42%.
- Combined chemo-photothermal therapy in 3D spheroids reduced viability to 16%, demonstrating superior efficacy.
Conclusions:
- 3D spheroids are essential for accurate in vitro screening of nanomedicine-based cancer therapies.
- Combined chemo-photothermal therapy using these nanoparticles is a highly promising strategy for solid tumors.
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