A novel mitoxantrone conjugate was synthesized by coupling mitoxantrone with ionic liquid tags, and cytotoxic behavior of the designed conjugate was studied in normal and cancer cell lines. The synthesized mitoxantrone conjugate was oil at physiological temperatures and demonstrated high aqueous solubility. Sensitivity of electrospray ionization mass spectrometry (ESI-MS) to the mitoxantrone conjugate was improved by an order of magnitude, in comparison with original mitoxantrone dihydrochloride. The observed ESI-MS signals were shifted to a "clearer" lower-mass region of the spectrum, which allowed investigation of the drug at the level of individual cells. The ionic liquid tags proposed in the present work consist of an easily available imidazolium salt residue and show a number of key advantages from the points of view of drug conjugate synthesis, drug delivery and analytic detection.
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http://dx.doi.org/10.1021/acs.analchem.7b03568 | DOI Listing |
Biomedicines
December 2024
Faculty of Medicine and Surgery, Università Vita-Salute San Raffaele, 20132 Milano, Italy.
Background/objectives: Standard chemotherapy is generally considered the best approach to treat many solid cancers, even accounting for severe side effects. Therefore, the development of a drug delivery system for chemotherapeutic administration could significantly improve standard chemotherapy by maintaining the cytotoxic effects of the drugs while decreasing the inherent side effects of the treatment. The aim of our study is the optimization of a loading strategy that conjugates the use of extracellular vesicles (EVs) as drug delivery carriers, by preserving their integrity, with the loading efficiency and activity maintenance of chemotherapeutics.
View Article and Find Full Text PDFPharm Dev Technol
January 2025
Guangxi Key Laboratory of Special Biomedicine, School of Medicine, Guangxi University, Nanning, China.
Adv Healthc Mater
November 2024
Department of General Surgery, Zhujiang Hospital, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
The immunosuppressive microenvironment severely limits the responsiveness of colorectal cancer (CRC) to immunotherapy. Herein, a pH and reactive oxygen species (ROS) dual-responsive autocatalytic release system (TPDM/PGA) is constructed to reverse the immunosuppressive microenvironment and potentiate CRC immunotherapy. Dihydroartemisinin (DHA) and mitoxantrone (MTO) are conjugated to ROS-responsive polyethylenimine (TP) via a ROS-cleavable linker, respectively, and then coated with polyglutamic acid (PGA) to endow pH and ROS dual-responsiveness.
View Article and Find Full Text PDFMolecules
August 2024
Department of Pharmacology, School of Medicine, University of Crete, 70013 Heraklion, Greece.
The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7.
View Article and Find Full Text PDFMicroPubl Biol
June 2024
Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, United States.
Pixantrone and mitoxantrone are structurally related anticancer drugs which have been shown to generate covalent conjugates at apurinic/apyrimidinic (AP) sites in DNA. Mitoxantrone binding to AP sites induces DNA strand cleavage and inhibits the endonuclease activity of human AP endonuclease 1 (APE1). Here, pixantrone was demonstrated to have similar properties, but relative to mitoxantrone, it was significantly less potent in both DNA incision and APE1 inhibition.
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