Poly(D,L-lactide-co-glycolide)-Lipid-poly(ethylene glycol) nanoparticles (PLGA-Lipid-PEG NPs), combining characteristics of both liposomes and polymeric nanoparticles, are new nanotherapeutic designs to treat different types of cancers. The activation of the complement system is one of the most important immunocompatibility studies that must be conducted to validate the clinical use of drug delivery carriers that will be administered via intravenous. The surface chemistry of such nanocarriers can cause hypersensitive reactions including cardiopulmonary diseases (e.g. tachycardia, hypotension, chest pain etc) which correlate with the activation of the complement system. Here we report for the first time a method to control the levels of complement activation of polymer-lipid nanoparticles. This method consists of the modification of the surface of polymeric-lipid nanoparticles with methoxyl, carboxyl and amine functional groups in a very specific manner. It was found that methoxyl-ends poly (D, L-lactide-co-glycolide)-Lipid-poly(ethylene glycol) nanoparticles showed the lowest complement activation, whereas amine-ends lipid polymeric nanoparticles rendered the highest level. All types of nanoparticles are found to activate the Alternative pathway but not the Classical pathway. In vivo studies are underway to investigate whether PLGA-Lipid-PEG-COOH NPs functionalized with A10 RNA aptamer activate the complement system. Our study shed light on understanding and improving the design of therapeutic nanoparticles for prostate cancer treatment.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 641.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009