title: Folate-decorated arginine-based poly(ester urea urethane) nanoparticles as carriers for gambogic acid and effect on cancer cells.
abstract: 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.
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, New York, 14853-4401.
authors.forename: Mingyu
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853.
authors.forename: Lillian
authors.initials: L
authors.lastname: Ro
authors.affiliation: Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, New York, 14853-4401.
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Chu
mesh_terms: D000072283:A549 Cells; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D044004:Xanthones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D044004:Xanthones; C497893:poly(ester urethane)urea; C052659:gambogic acid; D005492:Folic Acid
keywords: apoptosis; arginine; folate; gambogic acid; nanoparticles; polyurethane