Encapsulation of Mitoxantrone within Cucurbit[8]uril Decreases Toxicity and Enhances Survival in a Mouse Model of Cancer

ACS Medicinal Chemistry Letters
Shyam K KondaSuzanne M Cutts

Abstract

Mitoxantrone was efficiently encapsulated within cucurbit[8]uril in a 2:1 complex where the two mitoxantrone molecules were symmetrically located through both portals of a cucurbit[8]uril cage. The novel complex facilitates increased mitoxantrone uptake in mouse breast cancer cells and decreases the toxicity of the drug in healthy mice. In an orthotopic mouse model of metastatic breast cancer the complex still maintains in vivo anticancer activity compared to the free drug, yet provides a statistically significant increase in the survival of these mice compared to conventional mitoxantrone treatment. This new low toxicity formulation offers the possibility to increase mitoxantrone dose and thus maximize efficacy while managing the dose limiting side effects.

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Citations

Feb 17, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Meenakshi N ShindeAnupa A Kumbhar
Oct 2, 2019·Frontiers in Chemistry·Debapratim DasWerner M Nau
Jan 14, 2021·Chemical Society Reviews·George T WilliamsPhilip A Gale
Nov 25, 2020·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Riku KubotaTsuyoshi Minami
Jun 3, 2021·Nanomaterials·Alina AktanovaVladimir Kozlov
Jun 15, 2021·RSC Medicinal Chemistry·Zeyu WangRuibing Wang
Jul 25, 2021·International Journal of Molecular Sciences·Ekaterina PashkinaVladimir Kozlov

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