Integrative In Situ Photodynamic Therapy-Induced Cell Death Measurement of 3D-Bioprinted MCF-7 Tumor Spheroids

Area of Science:

• Biomedical Engineering
• Cancer Research
• Drug Development

Background:

• Developing accurate in vitro models of the tumor microenvironment (TME) is crucial for evaluating anticancer drug efficacy.
• Current models often fail to fully replicate the complex TME, limiting predictive power.

Purpose of the Study:

• To develop and validate a 3D bioprinted hydrogel model embedding MCF-7 cancer spheroids for in situ determination of photosensitizer (PS) half-maximal inhibitory concentration (IC50) values.
• To compare drug efficacy in this 3D model versus traditional 2D cultures.

Main Methods:

• Fabrication of MCF-7 cell-laden alginate/gelatin hydrogels to mimic the extracellular matrix (ECM).
• Utilizing the hydrogel to create 3D tumor spheroids for drug testing.
• Employing laser-based fluorescence to measure photodynamic therapy (PDT)-induced cell death in situ.
• Determining IC50 values for PSs (chlorin e6 and sulfonated tetraphenyl porphyrin) in both 3D and 2D models.

Main Results:

• The 3D model allowed for integrative in situ measurement of all tumor spheroids without individual separation.
• Significantly higher IC50 values for PSs were observed in the 3D spheroid-embedded hydrogels compared to 2D cultures, indicating increased drug resistance.
• Heterogeneous PDT responses and apoptosis within single spheroids were visualized, highlighting intra-tumor complexity.
• Laser-power-dependent IC50 values were successfully obtained using this 3D model.

Conclusions:

• The 3D bioprinted hydrogel model provides a more realistic in vitro platform for evaluating anticancer drugs, particularly photosensitizers.
• This model better reflects tumor spheroid drug resistance and heterogeneity compared to 2D cultures.
• The developed model facilitates efficient and accurate drug efficacy assessment and can reveal laser-power-dependent drug responses.