A tumor spheroid array chip for high-fidelity evaluation of liposomal drug delivery through the EPR effect

초록

Conventional two-dimensional (2D) culture systems fail to recapitulate the structural and functional complexity of the tumor microenvironment (TME), limiting their utility for preclinical drug evaluation. Here, we present a perfusable, high-throughput microfluidic Tumor Spheroid Array (TSA)-Chip that supports dynamic co-culture of tumor spheroids and vascular networks under perfusable conditions. The platform enables real-time visualization and quantitative analysis of nanoparticle transport, therapeutic response, and vascular remodeling. Fluorescent liposome tracking revealed EPR-like, tumor-selective accumulation, which was absent in 2D or tumor-free models. Liposomal 5-fluorouracil (5-FU) induced localized cytotoxicity and peritumoral vessel pruning while preserving overall vascular integrity. Furthermore, combination treatment with Cyramza (TM) (ramucirumab) enhanced tumor suppression and barrier normalization. Compared to conventional models, the TSA-chip offers robust analytical capabilities for assessing nanocarrier delivery and combination therapy effects in a scalable and physiologically relevant format, advancing its utility in precision oncology research.

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