Capecitabine

Cells were cultured in 2D plates and 3D plates as follows (determined on the basis of preliminary experiments): LoVo, 5,000 cells/well (2D) and 10,000 cells/well (3D); MDA-MB-231, 5,000 cells/well (2D) and 10,000 cells/well (3D). The drugs were added to the 2D plates after 24 h and to the 3D plates after 5 days. These drugs are 5-fluorouracil (5-FU), methotrexate (MTX), paclitaxel (PTX), oxaliplatin (OXA), irinotecan (CPT-11), and capecitabine with different concentration gradients (0.01, 0.1, 1, 10, and 100  $\mu$ M), which are purchased from Sinopharm Chemical Reagent (China). The sensitivity of cells to chemotherapeutic drugs was measured by CCK8 after 48 h of drugs treatment. Experimental control wells contained only cancer cells without drugs; experimental wells contained both cells and drugs; and blank control wells contained no cells or drugs.

LoVo human colon cancer and MDA-MB-231 human breast cancer cell lines were obtained from American Type Culture Collection (United States of America). 5-fluorouracil (5-FU), methotrexate (MTX), paclitaxel (PTX), oxaliplatin (OXA), irinotecan (CPT-11), and capecitabine were purchased from Sinopharm Chemical Reagent (China). CS was purchased from AK Biotech Co., Ltd. (China). Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), and phosphate-buffered saline (PBS) were from Gibco (USA). TPP was obtained from Invitrogen (USA). EDC, N-hydroxysuccinimide (NHS), lithium bromide, 1% penicillin-streptomycin, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich (USA). Glacial acetic acid was obtained from Sinopharm Chemical Reagent (China). Cell counting kit-8 (CCK-8) reagent was from Beyotime Biotechnology (China).