3D bioprinted breast tumor model for structure–activity relationship study

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.

Experimental and in silico studies on three hydrophobic charge-induction adsorbents for porcine immunoglobulin purification

Three hydrophobic charge-induction adsorbents with functional ligands of 4-mercapto-ethyl-pyridine, 2-mercapto-methyl-imidazole or 2-mercapto-benzimidazole were evaluated in the purification of porcine immunoglobulin from porcine blood. Adsorption isotherms were studied under different pH conditions. The adsorbent with 2-mercapto-methyl-imidazole as the ligand showed reasonable adsorption capacity(43.60 mg·g^(-1)gel)with great selectivity and it also showed the best elution performance in chromatographic studies. A multi-pH step elution process was proposed for the 2-mercapto-methyl-imidazole adsorbent, and the results showed that high immunoglobulin purity(94.3%) and a yield of 9.8 mg·(ml plasma)^(-1) could be achieved under the optimal condition of loading(pH 5.0)–pre-elution(pH 7.0)–elution(pH 3.8). Moreover, molecular simulation was employed to help in analyzing the binding mechanism between the ligands and immunoglobulin, and the results showed that both 2-mercapto-benzimidazole and 2-mercapto-methyl-imidazole ligands were docked on the same pocket(around TYR319 and LEU309) of the Fc fragment of immunoglobulin, with 2-mercaptobenzimidazole showing stronger binding interactions.