A hydrogel-based tumor model for the evaluation of nanoparticle-based cancer therapeutics.
作者： Xian Xu , Chandran R. Sabanayagam , Daniel A. Harrington , Mary C. Farach-Carson , Xinqiao Jia
DOI: 10.1016/J.BIOMATERIALS.2013.12.080
关键词:
摘要: Three-dimensional (3D) tissue-engineered tumor models have the potential to bridge gap between monolayer cultures and patient-derived xenografts for testing of nanoparticle (NP)-based cancer therapeutics. In this study, a hydrogel-derived prostate (PCa) model was developed in vitro evaluation doxorubicin (Dox)-loaded polymer NPs (Dox-NPs). The hydrogels were synthesized using chemically modified hyaluronic acid (HA) carrying acrylate groups (HA-AC) or reactive thiols (HA-SH). crosslinked hydrogel networks exhibited an estimated pore size 70-100 nm, similar spacing extracellular matrices (ECM) surrounding tissues. LNCaP PCa cells entrapped HA formed distinct tumor-like multicellular aggregates with average diameter 50 μm after 7 days culture. Compared grown on two-dimensional (2D) tissue culture plates, from engineered tumoroids expressed significantly higher levels multidrug resistance (MDR) proteins, including protein 1 (MRP1) lung resistance-related (LRP), both at mRNA levels. Separately, Dox-NPs 54 ± nm prepared amphiphilic block copolymers based poly(ethylene glycol) (PEG) poly(e-caprolactone) (PCL) bearing pendant cyclic ketals. able diffuse through matrices, penetrate into tumoroid be internalized by caveolae-mediated endocytosis macropinocytosis pathways. 2D cultures, cultured as more resistant Dox treatments. Moreover, NP-based formulation could bypass drug efflux function MRP1, thereby partially reversing free 3D cultures. Overall, has provide predictable results efficacy
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