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Folate‐decorated arginine‐based poly(ester urea urethane) nanoparticles as carriers for gambogic acid and effect on cancer cells
Author(s) -
He Mingyu,
Ro Lillian,
Liu Jing,
Chu ChihChang
Publication year - 2017
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35924
Subject(s) - gambogic acid , hela , cytotoxicity , materials science , nuclear chemistry , biocompatibility , nanoparticle , apoptosis , polymer , population , urea , cancer cell , polymer chemistry , chemistry , biochemistry , nanotechnology , in vitro , cancer , biology , composite material , metallurgy , demography , genetics , sociology
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.