An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity in vivo

Chemical Science
Josef MayrBernhard K Keppler

Abstract

The design of targeted platinum(iv) prodrugs is a very promising approach to enhance the low selectivity of platinum(ii) drugs towards cancerous tissue in order to reduce the impact on healthy tissue and, consequently, the often severe side-effects. Herein, we report a set of mono-functionalized cis- and oxaliplatin-based platinum(iv) complexes bearing a maleimide moiety, which allows selective binding to serum albumin in the bloodstream. This leads not only to a prolonged plasma half-life by avoidance of fast renal clearance, but also to preferential accumulation of the drug in the tumor tissue due to the EPR-effect. Additionally, analogous succinimide-functionalized derivatives were prepared to verify the influence of the maleimide moiety. First experiments showed that all the maleimide compounds are stable and also possess good albumin-binding properties in whole serum. Further analytical studies on in vivo samples proved the highly increased plasma half-life, as well as tumor accumulation of the maleimide-functionalized substances. In vivo antitumor experiments with CT-26-bearing mice showed that, in contrast to the cisplatin derivatives, the oxaliplatin-based complexes had exceptionally better activity than the free drug r...Continue Reading

References

Oct 1, 1995·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·M J McKeage
Apr 5, 2002·Journal of Inorganic Biochemistry·Rita SongYoun Soo Sohn
Jul 12, 2002·Cancer Chemotherapy and Pharmacology·Jocelyn L CarrMark J McKeage
Jul 18, 2002·The Journal of Biological Chemistry·Mark S DennisLisa A Damico
Sep 21, 2005·Cancer Chemotherapy and Pharmacology·Jocelyn L CarrMark J McKeage
Jun 3, 2006·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M R GreenM J Hawkins
Jun 28, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Aug 12, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dirk GarmannUlrich Jaehde
Oct 7, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cora N SternbergMarcel Rozencweig
Jul 2, 2010·Dalton Transactions : an International Journal of Inorganic Chemistry·Nial J WheateRabbab Oun
Mar 3, 2011·Inorganic Chemistry·Justin J Wilson, Stephen J Lippard
Nov 2, 2011·Current Topics in Medicinal Chemistry·Chee Fei ChinWee Han Ang
Aug 14, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Hristo P VarbanovBernhard K Keppler
Feb 12, 2013·Chemical Communications : Chem Comm·Verena PichlerChristian R Kowol
Jun 12, 2013·Free Radical Biology & Medicine·Lucía TurellBeatriz Alvarez
Jul 19, 2013·Inorganic Chemistry·Timothy C Johnstone, Stephen J Lippard
Sep 13, 2013·Anti-cancer Drugs·Raffaele Di FranciaMassimiliano Berretta
Jan 15, 2014·BMC Pharmacology & Toxicology·Marie ParelCatherine Rioufol
Mar 19, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Jun 7, 2014·Journal of the American Chemical Society·Yao-Rong ZhengStephen J Lippard
Aug 28, 2014·Frontiers in Physiology·Angelica M MerlotDes R Richardson
Nov 22, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sarah TheinerBernhard K Keppler
Jun 10, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Malin BernJan Terje Andersen
Jul 18, 2015·Molecular Cancer Therapeutics·Eva Martinez-BalibreaAlbert Abad
Oct 28, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Franco M MuggiaStephen B Howell
Jan 26, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Lauren Amable
Feb 18, 2016·Cancer Chemotherapy and Pharmacology·Shahana Dilruba, Ganna V Kalayda
May 24, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Dan Gibson

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Citations

Aug 30, 2018·Analytical and Bioanalytical Chemistry·Luis GalvezGunda Koellensperger
Dec 16, 2018·Angewandte Chemie·Pingyu ZhangPeter J Sadler
Mar 15, 2019·Angewandte Chemie·Alexander KastnerChristian R Kowol
May 17, 2019·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Trevor W Hambley
Aug 14, 2020·Chemical Communications : Chem Comm·Amarasooriya M D S JayawardhanaYao-Rong Zheng
Apr 14, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Josef MayrBernhard K Keppler
Aug 9, 2019·Cancer Chemotherapy and Pharmacology·J DelahousseA Paci
May 31, 2017·Chemistry, an Asian Journal·Zhenqin ZhangZijian Guo
Feb 8, 2018·Future Medicinal Chemistry·Muhammad Hanif, Christian G Hartinger
May 12, 2018·Drug Delivery and Translational Research·Wei WeiJin Sun
Jun 4, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Payel DattaYao-Rong Zheng
Aug 14, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Giulio BrescianiFabio Marchetti
Dec 20, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Jana HildebrandtWolfgang Weigand
Sep 22, 2018·Monatshefte für chemie·Matthias H M KloseBernhard K Keppler
Dec 12, 2020·Advanced Science·Bin YangHaijun Yu
Apr 22, 2021·ACS Applied Materials & Interfaces·Maichi HamaTatsuhiro Ishida
May 13, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Soghra Bagheri, Ali A Saboury
Jul 13, 2021·Chemical Communications : Chem Comm·Cinzia ImbertiPeter J Sadler
Aug 4, 2021·Journal of Medicinal Chemistry·Claudia SchmidtDan Gibson
Nov 30, 2018·Chemical Reviews·Bernhard EnglingerWalter Berger
Dec 14, 2018·Inorganic Chemistry·Xiyuan YaoUlrich Bierbach
Aug 18, 2021·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Andreia ValentePetra Heffeter
Apr 4, 2020·Bioconjugate Chemistry·Samuel M Meier-Menches, Angela Casini
Aug 11, 2017·Bioconjugate Chemistry·Anne C ConibearChristian F W Becker

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Methods Mentioned

BETA
NMR
X-ray
size exclusion chromatography
dynamic light scattering

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