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Multifunctional nanoparticles for co-delivery of paclitaxel and carboplatin against ovarian cancer by inactivating JMJD3-HER2 axis

Abstract

Ovarian cancer (OC) is the most lethal gynecologic cancer. Survival statistics showed no significant developments over the last three decades, highlighting the fact that current therapeutic strategies require substantial improvements. In this study, we designed a novel folic acid-PEG-conjugated p-phosphonated calix[4]arene nanoparticle (Fp-PCN) for simultaneous delivery of paclitaxel (PAC) and carboplatin (CAR) at an optimal ratio (5:1, mol:mol) to utilize their potential synergistic effect against OC cells. The Fp-PCN nanoparticle loaded with PAC and CAR (Fp-PCNPAC+CAR) resulted in a remarkable efficacy in suppression of OC both in vitro and in vivo. Compared to free drugs, Fp-PCNPAC+CAR showed stronger apoptosis induction as well as invasion and self-renewal capacity suppression in SKOV-3 cells. The molecular mechanism to address the synergism is that Fp-PCNPAC+CAR downregulated JMJD3 expression to modulate H3K27me3 epigenetic mark of the promoters of HER2 and MYCN. Furthermore, the expressions of JMJD3 and HER2 were significantly associated with poor outcomes for ovarian patients. Our study demonstrate that co-delivery of PAC and CAR can be achieved with Fp-PCN nanoparticles, and reveal a previously unrecognized and unexpected role of JMJD3-HER2 signaling axis in PAC and CAR treatment of OC.

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Publication details

The article was received on 21 Jun 2017, accepted on 31 Jul 2017 and first published on 03 Aug 2017


Article type: Paper
DOI: 10.1039/C7NR04473A
Citation: Nanoscale, 2017, Accepted Manuscript
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    Multifunctional nanoparticles for co-delivery of paclitaxel and carboplatin against ovarian cancer by inactivating JMJD3-HER2 axis

    J. Mo, L. Wang, X. Huang, B. Lu, C. Zou, L. Wei, J. Chu, P. Eggers, S. Chen, C. L. Raston, J. Wu, L. Lim and W. Zhao, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR04473A

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