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Chemistry for Life/Chemistry for Medicine Seminar

27 May 2021, 12:00 pm–1:00 pm

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Nanomedicines to Deliver Dual-Targeting Dual-Action PT (IV) Chemotherapeutic Complexes for Enhanced Anticancer Activity and Reduced Nephrotoxicity

This event is free.

Event Information

Open to

UCL staff | UCL students

Availability

Yes

Cost

Free

Organiser

Prof. Stefan Howorka

Location

Virtual
Via Zoom
London
WC1H 0AJ
United Kingdom

Abstract

Introduction: The discovery of cisplatin as a (Pt)-based anti-cancer drug in 1965 was an important milestone. Nowadays, cisplatin and its analogues, all acting at the nuclear DNA as their biological target, are still used in 40% of all chemotherapy treatments. However, these drugs have toxic side effects (e.g. kidney dysfunction). Hence, we have conceived a novel dual-targeting platform to ensure strategic delivery of dual-action Pt prodrugs.

Materials & methods: The first targeting was established by liposomal nanoencapsulation of Pt complexes (including cisplatin and mitochondrial sensitizers) to attain high accumulation [1] at the tumor site. After the release of the Pt prodrug inside cancer cells, a second stage of targeting directed the Pt prodrugs to the mitochondria [2]. Upon intracellular reduction, these Pt prodrugs released two bioactive molecules [3], acting on the mitochondrial and on the nuclear DNA [4].

Results: Our Pt system showed excellent activity, characterized by low micromolar cytotoxicity and complete tumor remission in vivo, accompanied by reduced kidney toxicity [3].

Conclusion: The research findings provide insights into the potential of nanomedicine to reach the diseased area, protect the incorporated bioactive molecules from premature deactivation and enhance delivery of drugs at the mitochondria while decreasing their side effects.

References:

1. Sia Lee Yoong, Bin Sheng Wong, Qi Lin Zhou, Chee Fei Chin, Jian Li, Thirumalai Venky Venkatesan, Han Kiat Ho, Victor Chun Kong Yu, Wee Han Ang*, Giorgia Pastorin*. Enhanced Cytotoxicity to Cancer Cells by Mitochondria-targeting MWCNTs Containing Platinum(IV) Prodrug of Cisplatin. Biomaterials, 2014, 35(2), 748–759.

2. Sia Lee Yoong, Wei Liang Lau, Ang Yu Liu, D’Arcy Prendergast, Han Kiat Ho, Victor Chun Kong Yu, Chengkuo Lee, Wee Han Ang,* and Giorgia Pastorin*. Mitochondria-acting Hexokinase II Peptide Carried by Short-length Carbon Nanotubes with Increased Cellular Uptake, Endosomal Evasion, and Enhanced Bioactivity Against Cancer Cells. Nanoscale, 2015, 7, 13907 – 13917.

3. Chee Fei Chin, Siew Qi Yap, Jian Li, Giorgia Pastorin* and Wee Han Ang*. Ratiometric Delivery of Cisplatin and Doxorubicin using Tumour-Targeting Carbon-Nanotubes Entrapping Platinum(IV) Prodrugs. Chemical Science, 2014, 5, 2265-2270.

4. Maria V. Babak, Yang Zhi, Bertrand Czarny, Tan Boon Toh, Lissa Hooi, Edward Kai-Hua Chow, Wee Han Ang,* Dan Gibson* and Giorgia Pastorin*. Dual-targeting Dual-action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity. Angew. Chemie Int. Ed., 2019, 58, 1-7.

Also presenting is Dr. Daniel Whitaker (UCL Departmental of Chemistry) who will speak about the plausibility of prebiotic aminonucleotide formation

About the Speaker

​Dr Giorgia Pastorin

at Department of Pharmacy, National University of Singapore

Giorgia Pastorin received her MSc degree in Pharmaceutical Chemistry and Technology in 2000 and her Ph.D. in 2004 from the University of Trieste (Italy). She spent two years of her postDoc at the CNRS in Strasbourg (France), where she specialized on drug delivery.
She joined the National University of Singapore (NUS) in June 2006, as Assistant Professor in the Department of Pharmacy-Faculty of Science. She was promoted to Associate Professor in 2011, Assistant Head in 2014 and Deputy Head in 2016; she is currently Assistant Dean (Research) at the Faculty of Science and Director of the Pharmaceutical Innovation and Research Center in NUS.
Her main research interests include production, characterization & exploitation of cell-derived nanovesicles (CDNs) as novel biocompatible delivery systems and targeted drug delivery, through strategic functionalizations of nanomaterials and pro-drugs.

She is the Editor of two books related to drug delivery and author in more than 140 articles on internationally peer-reviewed journals including Nature Nanotechnology, Biomaterials, Angewandte etc.
For the work performed by her BioNano-Technology group in NUS, she received the Young Scientist Award (2015).