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Title: Calixarene nanovesicles for drug delivery

Jingxin Mo

Guilin Medical University, China

Biography

Dr. Jingxin Mo studied Pharmacy at the Guilin Medical University, China and graduated as MS in 2002. He then obtained his master decree in 2008 at the West China School of Pharmacy, Sichuan University, China. He received his PhD degree in Key Laboratory of Drug Targeting and Drug Delivery Systems of Prof. Zhang in 2011 at the same school. After four years’ postdoctoral fellowship cooperated with Prof. LIM at the School of Allied Health, University of Western Australia, WA, Australia. He obtained the position of a Research Professor at the Zhongshan Medical School, Sun Yat-sen University before moving to the The First Affiliated Hospital, Guilin Medical University as Professor and deputy director of Neuroscience Clinical Research Center. He has published more than 10 research articles in SCI(E) journals as first author or corresponding author. He got more than 1 million CNY funding for this research group.

Abstract

Ovarian cancer (OC) is the most lethal gynecologic cancer. Survival statistics have shown 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. Our results reveal that calixarenes display selectivity in disrupting the association of JMJD3 with the methylated histone H3K27 tail. We show that the calixarene activity relies on differences in binding affinities of the JMJD3 for H3K27me3.
Audience take away:
• Calixarene, a novel, versatile and potent platform for drug delivery.
• Next generation of delivery system, which précisedly deliver its payload to biomolecular level, compared to traditional targeted delivery system, which targetedly deliver its payload to organ, cell or sub-cell levels.
• Novel anti-cancer mechanism, by influencing epigenetic signaling path ways for better treatment of cancer.