Polycyanoacrylate polymeric nanoparticles loaded with cabazitaxel: Comparison of organ distribution and mammary cancer inhibition
Nanoparticles (NPs) to improve drug delivery to cancer treatment are of high interest. Nanoparticle drug delivery systems try to improve the cancer therapy by using targeting to the tumors and thereby increase specificity of chemotherapeutic drugs. Here, we will use various polymeric polycyanoacrylate nanoparticles with a polyethylene (PEG) surface to encapsulate the chemotherapeutic drug cabazitaxel. The particles are different in polymer composition and PEG surface structure.
The distribution of these NPs in tumor-bearing mice will be investigated, and the accumulation of particle and the thereby released drug will be quantified. Cabazitaxel is a taxane derivative that is used in the clinic and is tested against several breast cancer subtypes in clinical trials. In this study, we want to further test if incorporation of cabazitaxel into biodegradable polycyanoacrylate nanoparticles can inhibit breast cancer growth and reduce adverse effects when compared to the drug alone. These experiments might provide the basis for future clinical applications.
Folate receptors (FR) are highly expressed (500 times more than healthy cells) on epithelial cancer cells such as breast cancer.
As a result, the high affinity of FA for folate receptors provides a unique opportunity for the specific targeting and delivery of nanoparticles to cancer cells. The targeting of the folate receptor has been shown considerably promising in mediating uptake of a variety of drugs, and several experiments showed that there is a significant uptake difference by folate-targeted liposomes between cells with overexpression and those with no expression of folate receptors. As an extension of the current study, we want to study PACA NPs, mentioned in this study, with folate on surface for actively targeting cancer cells.
The mice will get tumors implanted orthotopically into their mammary fat pad and will receive treatment with chemotherapeutic drugs, this can result in loss of body weight or lead to impaired movement because of high tumor size. If we observe any signs of severe symptoms, we will limit the harm to the animals to as short as possible. Previous experiments have been shown that the anesthesia and the in vivo imaging are well tolerated.
We apply for a total of 348 athymic nude mice. We aim to replace and reduce the number of animals and try to refine the procedures. The efficacy of cancer treatment and the distribution of nanoparticles and cancer drugs in an organism are complex and till-date there are no techniques that can predict these results. The number of mice is as low as possible but high enough that it is still possible to find significant differences.
The distribution of these NPs in tumor-bearing mice will be investigated, and the accumulation of particle and the thereby released drug will be quantified. Cabazitaxel is a taxane derivative that is used in the clinic and is tested against several breast cancer subtypes in clinical trials. In this study, we want to further test if incorporation of cabazitaxel into biodegradable polycyanoacrylate nanoparticles can inhibit breast cancer growth and reduce adverse effects when compared to the drug alone. These experiments might provide the basis for future clinical applications.
Folate receptors (FR) are highly expressed (500 times more than healthy cells) on epithelial cancer cells such as breast cancer.
As a result, the high affinity of FA for folate receptors provides a unique opportunity for the specific targeting and delivery of nanoparticles to cancer cells. The targeting of the folate receptor has been shown considerably promising in mediating uptake of a variety of drugs, and several experiments showed that there is a significant uptake difference by folate-targeted liposomes between cells with overexpression and those with no expression of folate receptors. As an extension of the current study, we want to study PACA NPs, mentioned in this study, with folate on surface for actively targeting cancer cells.
The mice will get tumors implanted orthotopically into their mammary fat pad and will receive treatment with chemotherapeutic drugs, this can result in loss of body weight or lead to impaired movement because of high tumor size. If we observe any signs of severe symptoms, we will limit the harm to the animals to as short as possible. Previous experiments have been shown that the anesthesia and the in vivo imaging are well tolerated.
We apply for a total of 348 athymic nude mice. We aim to replace and reduce the number of animals and try to refine the procedures. The efficacy of cancer treatment and the distribution of nanoparticles and cancer drugs in an organism are complex and till-date there are no techniques that can predict these results. The number of mice is as low as possible but high enough that it is still possible to find significant differences.