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Issue 35, 2017
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Multifunctional nanoparticles for co-delivery of paclitaxel and carboplatin against ovarian cancer by inactivating the JMJD3-HER2 axis

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Abstract

Ovarian cancer (OC) is the most lethal gynecologic cancer. Survival statistics have show 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 the 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-PCNs loaded with PAC and CAR (Fp-PCNPAC+CAR) resulted in a remarkable efficacy in the 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 the 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 demonstrates that co-delivery of PAC and CAR can be achieved with the Fp-PCNs, and reveals a previously unrecognized and unexpected role of the JMJD3-HER2 signaling axis in PAC and CAR treatment of OC.

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

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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, 2017,9, 13142-13152
  • Open access: Creative Commons BY license
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    Multifunctional nanoparticles for co-delivery of paclitaxel and carboplatin against ovarian cancer by inactivating the JMJD3-HER2 axis

    J. Mo, L. Wang, X. Huang, B. Lu, C. Zou, L. Wei, J. Chu, P. K. Eggers, S. Chen, C. L. Raston, J. Wu, L. Y. Lim and W. Zhao, Nanoscale, 2017, 9, 13142
    DOI: 10.1039/C7NR04473A

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