Reduction-responsive dehydroepiandrosterone prodrug nanoparticles loaded with camptothecin for cancer therapy by enhancing oxidation therapy and cell replication inhibition.

International Journal of Pharmaceutics
Congjun XuChunshun Zhao

Abstract

The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles PsD@CPT to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition. Following cellular uptake, DHEA and CPT were released from PsD@CPT in the presence of high glutathione (GSH) levels. As expected, DHEA-mediated reduction level decreases and CPT-induced oxidation level increases synergistically, breaking the redox balance to aggravate cancer oxidative stress. In addition, suppressing nucleotide synthesis by DHEA through the reduction of Ru5P and blocking DNA replication by CPT further motivates a synergistic inhibition effect on tumor cell proliferation. The results showed that PsD@CPT featuring multimodal treatment has satisfactory antitumor activity both in vitro and in vivo. This study provides a ...Continue Reading

References

Apr 1, 1995·Archives of Biochemistry and Biophysics·G GordonH R Levy
Feb 24, 2001·Annals of the New York Academy of Sciences·L F LiuS P Sim
Oct 31, 2002·The Journal of Biological Chemistry·Bernard L Horecker
Feb 24, 1956·Science·O WARBURG
Jun 5, 2004·Ageing Research Reviews·Arthur G Schwartz, Laura L Pashko
Oct 5, 2006·International Journal of Cancer. Journal International Du Cancer·Antonio Ramos-MontoyaMarta Cascante
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Apr 18, 2012·Journal of Medicinal Chemistry·Niall M HamiltonDonald J Ogilvie
Jul 20, 2014·Trends in Biochemical Sciences·Krushna C Patra, Nissim Hay
Jan 16, 2016·Cell Metabolism·Natalya N Pavlova, Craig B Thompson
Apr 18, 2016·International Journal of Pharmaceutics·Jing WangYongjun Wang
Jun 5, 2016·Cancer Biology & Therapy·Rebeca López-MarureErika Olivia Gómez-González
Jul 8, 2016·Science Advances·Ralph J DeBerardinis, Navdeep S Chandel
Jul 6, 2017·Advanced Drug Delivery Reviews·Raoul WaltherAlexander N Zelikin
Aug 27, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yuanfeng HeChunshun Zhao
Dec 8, 2017·Biomolecules & Therapeutics·Eunae Sandra ChoJong In Yook
May 10, 2018·Frontiers in Oncology·Maria Chiara De SantisAndrea Morandi
May 11, 2018·Chemical Communications : Chem Comm·Qiling ChenZhiqiang Yu
Feb 28, 2020·Asian Journal of Pharmaceutical Sciences·Yongbing SunZhiqiang Yu
Jun 24, 2020·Nature Chemical Biology·Michael E Pacold

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