Abstract 2308: Selective targeting of HeLa cervical cancer cells using folate receptor targeting drug loaded PLGA-lipid hybrid nanoparticles

Abstract

Abstract The response rate of breast cancer to first line chemotherapies is encouraging, but 20-30% of patients develop chemoresistance to these drugs, and consequently, have a cancer reoccurrence 7-10 months after their last treatment. Chemoresistance is believed to be due to drug efflux proteins responsible for the removal of many commonly used anti-neoplastic agents. One possible way to overcome these drug efflux pumps is to give higher doses of chemotherapy, but high doses of such agents commonly lead to chemocytotoxicity. Targeted PLGA-Lipid hybrid nanoparticle (NP) drug delivery systems have been developed that can deliver high doses of chemotherapy agents specifically to breast cancer cells. A practical cancer targeting drug delivery system will reduce the overall amount of chemotherapy agents given to patients for a given amount of targeted NPs endocytosed by cancer cells. Biodegradable NPs were synthesized using a novel nano-precipitation lipid-polymer hybrid platform which also allows for the encapsulation of hydrophobic chemotherapy drugs within the NPs. Using this method, drug free NPs have been shown to have an average diameter size of 81.78 nm (PDI: 0.25), while single loaded NPs, with Paclitaxel or Doxorubicin, show an average size between 72.33 to 89.64 nm (PDI: 0.242 to 0.339), signifying that the synthesis technique creates consistent sub 100nm particles. The majority of all NPs show a zeta-potential value of > -30 mV consistent with the NPs having sufficient repulsive interaction to be mono-dispersed in solution under physiological conditions. Folate receptors are often over expressed on the surfaces of cancer cells; therefore, folic acid was incorporated to the surface of these NPs as a cancer targeting ligand. Previous studies have shown that HeLa cells, a cervical cancer cell line, over expresses folate receptors. Immunofluorescence studies show that folic acid coated PLGA-Lipid hybrid NPs are readily endocytosed by HeLa cells compared to non-targeted NPs. Cytoxicity studies will determine the increased effectiveness of drug delivery with targeted PLGA-Lipid hybrid NPs vs. untargeted PLGA-Lipid hybrid NP in cell lines and in animal models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2308. doi:10.1158/1538-7445.AM2011-2308