Ultrasound mediated delivery of drug loaded nanoparticles for the treatment of subcutaneous tumors
The overall aim of the present project is to improve cancer therapy by enhancing the delivery of NPs to subcutaneous tumors by combining ultrasound and microbubbles with a novel dual targeting enzyme sensitive lipid based drug delivery system. The nanocarrier system is based on matrix metalloprotease(MMP) activatable liposomes. The drug loaded liposomes will have a PEG-coat that can be cleaved by the enzyme MMP, revealing the particle surface which will facilitate the delivery of the drugs to the tumor cells. Since MMPs are overexpressed in tumor tissue, it is expected that efficient and local drug release will be achieved, after tumor accumulation.
In our previous study (FOTS ID 11545) we have intensively worked with these novel nanoparticles and investigated the most optimal ultrasound settings for ultrasound mediated delivery of the novel nanoparticles. Furthermore we investigated the effect of ultrasound and microbubbles on the delivery of the nanoparticles in the tumor by studying the microdistribution and biodistribution. Based on the results we saw an improved, but different degree of delivery of all the three nanoparticles tested, when ultrasound and microbubbles were used. Now we would like to study if an improved delivery will also result in an increased cellular uptake and treatment effect when the nanoparticles are loaded with a chemotherapeutic drug. We will be especially interested in the treatment effect of our enzyme sensitive nanoparticle and compare its efficacy with its non-enzyme sensitive counter part and a clinically and commercially available nanoparticle. Before starting with the main treatment study, we will perform a short dose study to make sure that the dose of chemotherapeutic drug we will be using, will have an effect on the tumor growth.
To investigate all this we apply for 110 animals which we expect will have minimal distress. We have reduced the amount of groups and animals by only using the most efficient ultrasound settings found during our previous study. In case they do show signs of pain or discomfort, they will receive pain medication or other measures to end the discomfort.
In our previous study (FOTS ID 11545) we have intensively worked with these novel nanoparticles and investigated the most optimal ultrasound settings for ultrasound mediated delivery of the novel nanoparticles. Furthermore we investigated the effect of ultrasound and microbubbles on the delivery of the nanoparticles in the tumor by studying the microdistribution and biodistribution. Based on the results we saw an improved, but different degree of delivery of all the three nanoparticles tested, when ultrasound and microbubbles were used. Now we would like to study if an improved delivery will also result in an increased cellular uptake and treatment effect when the nanoparticles are loaded with a chemotherapeutic drug. We will be especially interested in the treatment effect of our enzyme sensitive nanoparticle and compare its efficacy with its non-enzyme sensitive counter part and a clinically and commercially available nanoparticle. Before starting with the main treatment study, we will perform a short dose study to make sure that the dose of chemotherapeutic drug we will be using, will have an effect on the tumor growth.
To investigate all this we apply for 110 animals which we expect will have minimal distress. We have reduced the amount of groups and animals by only using the most efficient ultrasound settings found during our previous study. In case they do show signs of pain or discomfort, they will receive pain medication or other measures to end the discomfort.