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Title: Self‐Assembled Oleic Acid Nanoparticle Mediated Inhibition of Mitogen‐Activated Protein Kinase Signaling in Combination with DNA Damage in Cancer Cells
Authors: Palvai, Sandeep
More, Piyush
Mapara, Nikunj
Nagraj, Jyothi
Chowdhury, Rajdeep
Dept. of Chemistry
Keywords: Self?Assembled Oleic Acid
Nanoparticle Mediated Inhibition
Mitogen-Activated Protein
Kinase Signaling
DNA Damage
Cancer Cells
MAPK inhibitors
Issue Date: Mar-2016
Publisher: Wiley
Citation: ChemNanoMat, 2(3), 201-211.
Abstract: Mitogen‐activated protein kinase (MAPK) signaling has been dysregulated in different types of cancers. However, targeting MAPK signaling with small molecules leads to severe toxic side effects to the patients as well as manifestation of drug resistance. To address these, we have developed 120 nm sized self‐assembled, biocompatible, biodegradable oleic acid nanoparticles (OA‐NPs) which can simultaneously contain AZD6244 (MAPK inhibitor) and cisplatin (DNA damaging drug). These OA‐NPs released AZD6244 and cisplatin in increased amount in pH 5.5 compared to pH 7.4 in a slow and sustained manner over 4 days with excellent stability at 4 °C for 2 months in water and in blood circulation mimic for 6 days. Moreover, these OA‐NPs showed much improved in vitro cytotoxicity in cervical cancer (HeLa) and triple negative breast cancer (MDA‐MB‐231) cells at 48 h and in hepatocellular carcinoma (Hep3B) and cisplatin‐resistant hepatocellular carcinoma (Hep3B‐R) cells at 24 h. In HeLa cells, these OA‐NPs induced apoptosis through inhibiting MAPK signaling and damaging DNA after being internalized through macropinocytosis and homed into the acidic lysosomal compartments. These OA‐NPs have the potential to be translated into the clinic for targeting multiple oncogenic signaling pathways and damaging DNA concurrently for augmented efficacy, reduced toxicity, and overcoming drug resistance in next‐generation cancer treatment.
ISSN: 2199-692X
Appears in Collections:JOURNAL ARTICLES

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