We treated the organoids with the e

We treated the organoids with the ellipticineloaded micelles for 2 d and observed different morphology of the organoids, as shown in figure 5(E).The organoids cultured in the Matrigel dome exhibited significant disaggregation, and 80% of cells werekilled, as shown by live/dead staining (figure 5(F)).The organoids developed on the chip without peristalsis showed slight disaggregation, and about 45%of cells died. The organoids developed under theperistalsis maintained their original morphology, andonly approximately 20% of cells were dead. The result indicates that the human colon tumor organoidsdeveloped under peristalsis may lead to a dull cellularresponse to nanoparticle treatment.We hypothesized that the peristalsis disturbs theendocytosis of the organoids and thus hinders thecellular uptake of micelles. After treatment withchlorpromazine (CPA), an inhibitor for clathrindependent endocytosis, the CPA-treated organoidsshowed significantly decreased uptake of the micelles(figure 5), indicating a clathrin-dependent endocytosis uptake pathway. These results shed light on thedevelopment of nanomedicines for tumors underperistalsis or cyclical contraction, where screening instatic gel domes is likely to exaggerate the effectivenessof the therapeutic