Optimization of acoustic cluster therapy for nanoparticle delivery into pancreatic tumors.
Previous studies showed the feasibility of the acoustic cluster therapy (ACT) technology to improve chemotherapy efficacy fn xenograft human prostate cancer (PC3) tumor. Today a lot of chemotherapeutic drugs are loaded into nanoparticles. However, the delivery of chemotherapeutic drug-loaded nanoparticles (NPs) has to be enhanced to be more effective. In this study we investigate the ACT effect on local nanoparticle delivery in the clinical relevant pancreatic ductal adenocarcinoma (PDAC) tumor model. The PDAC tumor model is chosen as we are planning ‘first ACT in man’ clinical studies end of 2018. The ultimate goal of ACT is to improve cancer therapy, thus preclinical experiments in mice is required. To obtain data that can be extrapolated to a clinical situation an intact circulation and tumors growing in a living animal is necessary.
Within this project, the ACT platform will be optimized for enhanced intra-tumoral accumulation and distribution of model-drug/dye loaded-NPs in pancreatic cancer. Furthermore, the mechanisms of action and theranostic characteristics of ACT will be studied. To limit the number of mice also in vitro studies using organs-on-a-chip and gel-based phantoms will be performed. However, it is not possible to mimic the complex vascular system of human tumors in phantom studies. Therefore, it is not possible to translate in vitro ACT-effect one-on-one to its behavior in patients and are in vitro studies alone not sufficient to predict its behavior in patients.
A total of 561 C57BL/6 mice will be used over a total of 7 sub-studies. We expect that they will have moderate distress. Animals are monitored daily.The mice will have cancer and some of them surgery, but they will not have to suffer because of humane endpoints and the use of anesthesia and analgesia.
Within this project, the ACT platform will be optimized for enhanced intra-tumoral accumulation and distribution of model-drug/dye loaded-NPs in pancreatic cancer. Furthermore, the mechanisms of action and theranostic characteristics of ACT will be studied. To limit the number of mice also in vitro studies using organs-on-a-chip and gel-based phantoms will be performed. However, it is not possible to mimic the complex vascular system of human tumors in phantom studies. Therefore, it is not possible to translate in vitro ACT-effect one-on-one to its behavior in patients and are in vitro studies alone not sufficient to predict its behavior in patients.
A total of 561 C57BL/6 mice will be used over a total of 7 sub-studies. We expect that they will have moderate distress. Animals are monitored daily.The mice will have cancer and some of them surgery, but they will not have to suffer because of humane endpoints and the use of anesthesia and analgesia.