Hydrogel Microtumor Arrays to Evaluate Nanotherapeutics

Nanoparticle drug formulations have many advantages for cancer therapy due to benefits in targeting selectivity, lack of systemic toxicity, and increased drug concentration in the tumor microenvironment after delivery. However, the promise of nanomedicine is limited by preclinical models that fail to accurately assess new drugs before entering human trials. In this work a new approach to testing nanomedicine using a microtumor array formed through hydrogel micropatterning is demonstrated. This technique allows partitioning of heterogeneous cell states within a geometric pattern-where boundary regions of curvature prime the stem cell-like fraction-allowing to simultaneously probe drug uptake and efficacy in different cancer cell fractions with high reproducibility. Using melanoma cells of different metastatic potential, a relationship between stem fraction and nanoparticle uptake is discovered. Deformation cytometry reveals that the stem cell-like population exhibits a more mechanically deformable cell membrane. Since the stem fraction in a tumor is implicated in drug resistance, recurrence, and metastasis, the findings suggest that nanoparticle drug formulations are well suited for targeting this dangerous cell population in cancer therapy.

Automated summary

Nanoparticle drug formulations have advantages in cancer therapy, but the assessment of new drugs is limited by preclinical models. This study demonstrates a new approach to test nanomedicine using a microtumor array formed through hydrogel micropatterning. It allows simultaneous evaluation of drug uptake and efficacy in different cancer cell fractions with high reproducibility. The findings suggest that nanoparticle drug formulations are well suited for targeting the stem cell-like population in cancer therapy due to their relationship with drug resistance, recurrence, and metastasis.