摘要
In this paper,we present a 3D printed tumor spheroidal model suitable for drug discovery.This model is based on a hydroxyethyl cellulose/alginate/gelatin(HCSG)composite biomaterial that has three distinct properties:(1)the HCSG is similar to the commercial basement membrane extract in Ki67,MUC1,and PARP1 expressions of MCF-7 cells for embedding culture;(2)the HCSG is printable at room temperature;and(3)the HCSG can be large-scale manufactured at an ultralow cost.We printed a 3D MCF-7 spheroid model with HCSG and characterized it in terms of cell viability,spheroid size,key protein expression,and mitochondrial metabolic activity.We used the 3D MCF-7 spheroid model to evaluate the anti-breast cancer activity of 13 amino acid-based flavone phosphoramidates and found that the alanine structure induced a stronger drug resistance,whereas phenylalanine hardly caused drug resistance in the MCF-7 cells.This is the first time that 3D bioprinting technology has been used in a structure–activity relationship study.
基金
This work was supported by the National Natural Science Foundation of China(No.21675017)
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products(KF20190108)
the National Key Research and Development Program of China(No.2017YFC1702001).And we thanked Prof.Yueqing Li for the synthesis of the isoflavone derivatives and useful discussions。
