Folate-decorated arginine-based poly(ester urea urethane) nanoparticles as carriers for gambogic acid and effect on...

Gambogic acid (GA) exhibits a broad spectrum of anticancer activity and low chemotoxicity to normal tissues. However, poor aqueous solubility and sensitivity to hydrolysis make its pharmaceutical applications a challenge. Linear and branched Arg-based poly(ester urea urethane)s (Arg-PEUUs), folate (FA)-conjugated Arg PEUUs (FA-Arg-PEUUs), and their self-assembled nanoparticles (NPs) were designed, synthesized, and studied as the potential GA carriers for cancer treatment. The average diameters of linear or branched Arg-PEUU/FA-Arg-PEUU NPs were 98-267 nm. FA-Arg-PEUU NPs adhered onto and were internalized into HeLa and A549 cells, and showed no cytotoxicity. The GA loading efficiency in the NP carriers ranged from 40 to 98%, depending on the feed weight ratio of GA to Arg-PEUU and the Arg-PEUU polymer structure (i.e., linear vs. branched). The GA at 2 µg/mL concentration delivered by the FA-Arg-PEUU NP carriers had higher cytotoxicity and induced a higher apoptosis percentage against folate receptor (FR)-overexpressed HeLa or HCT116 than Arg-PEUU NPs. When compared to the free GA treatment, the GA loaded in the FA-Arg-PEUU NP carriers also led to significant loss of the mitochondrial membrane potential in a higher percentage of the cancer cell population and more DNA fragmentation. The GA loaded in FA-Arg-PEUU NP carriers at as low as 0.6 µg/mL GA concentration led to lower MMP-2 and MMP-9 activity of cancer cells compared to free GA, suggesting that GA-loaded Arg-PEUU NPs may have greater potential to reduce cancer cell invasion and metastasis than free GA. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 475-490, 2017.