A PDA-Functionalized 3D Lung Scaffold Bioplatform to Construct Complicated Breast Tumor Microenvironment for Anticancer Drug Screening and Immunotherapy.

2D cell culture occupies an important place in cancer progression and drug discovery research. However, it limitedly models the "true biology" of tumors in vivo. 3D tumor culture systems can better mimic tumor characteristics for anticancer drug discovery but still maintain great challenges. Herein, polydopamine (PDA)-modified decellularized lung scaffolds are designed and can serve as a functional biosystem to study tumor progression and anticancer drug screening, as well as mimic the tumor microenvironment. PDA-modified scaffolds with strong hydrophilicity and excellent cell compatibility can promote cell growth and proliferation. After 96 h treatment with 5-FU, cisplatin, and DOX, higher survival rates in PDA-modified scaffolds are observed compared to nonmodified scaffolds and 2D systems. The E-cadhesion formation, HIF-1 & alpha;-mediated senescence decrease, and tumor stemness enhancement can drive drug resistance and antitumor drug screening of breast cancer cells. Moreover, there is a higher survival rate of CD45(+)/CD3(+)/CD4(+)/CD8(+) T cells in PDA-modified scaffolds for potential cancer immunotherapy drug screening. This PDA-modified tumor bioplatform will supply some promising information for studying tumor progression, overcoming tumor resistance, and screening tumor immunotherapy drugs.