Synergistic Image-guided Nanoparticles for Drug Delivery (SIN-Drug)

点击翻译按钮获取中文摘要

This project aims at inorganic-organic hybrid nanoparticles (IOH-NPs) as novel, multifunctional base materials for synergistic tumor therapy. IOH-NPs are designated by an unprecedentedly high drug load (70-85 wt-%), low material complexity and water-based synthesis. The challenge is to combine different cytostatic agents (up to three) with high drug load (>20 wt-% of each) into homogeneously composed nanoparticles. Besides the cytostatic effect of these multi-drug IOH-NPs, they are additionally intended to allow magnetothermal and/or photoactivated physical tumor treatment as well as multimodal imaging (OI, MRI). The IOH-NPs have a saline composition [GdO]+[(R1CytostaticCOO)a(R2CytostaticCOO)b(R3CytostaticOPO3)c(RDyeSO3)d]– with the paramagnetic, inorganic [GdO]+ cation and a combination of up to four functional anions (a+b+c+d = 1) including up to three cytostatic anions ([R1CytostaticCOO]–, [R2CytostaticCOO]–, [R3CytostaticOPO3]2–) and a fluorescent, ROS-generating anion ([RDyeSO3]–).Besides fundamental material synthesis and characterization (chemistry, Karlsruhe Institute of Technology), detailed in vitro and in vivo studies will be performed (medicine, University Medical Center Göttingen) to evaluate tumor-specific uptake, biocompatibility and biodistribution, drug release and pharmacokinetics, as well as the cytotoxic (anti-tumor) activity of the IOH-NPs in regard of pancreatic ductal adenocarcinoma (PDAC) as a most relevant tumor entity. As a most ambitions overall aim, the multi-drug IOH-NPs are intended to become part of a universal multimodal and multifunctional therapeutic and diagnostic platform that can be transferred to almost every type of solid tumor and that especially allows to reduce side effects and to minimize drug resistances.