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


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.

SUBMITTER: Konda SK 

PROVIDER: S-EPMC5430389 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Konda Shyam K SK   Maliki Ruqaya R   McGrath Sean S   Parker Belinda S BS   Robinson Tina T   Spurling Alex A   Cheong Alison A   Lock Peter P   Pigram Paul J PJ   Phillips Don R DR   Wallace Lynne L   Day Anthony I AI   Collins J Grant JG   Cutts Suzanne M SM  

ACS medicinal chemistry letters 20170424 5


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 <i>in vivo</i> anticancer activity compared to the free drug, yet provides a  ...[more]

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