期刊
MOLECULAR PHARMACEUTICS
卷 20, 期 8, 页码 3937-3946出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.3c00078
关键词
acute myeloid leukemia; nanomedicine; liposomaldrug encapsulation; sphingosine kinase 1
Liposome-based delivery system of MP-A08 enhances its potency against AML cells and significantly prolongs overall survival in mice with human AML disease, indicating its potential as a novel treatment for AML.
Acute myeloid leukemia (AML) kills75% of patients and representsa major clinical challenge with a need to improve on current treatmentapproaches. Targeting sphingosine kinase 1 with a novel ATP-competitive-inhibitor,MP-A08, induces cell death in AML. However, limitations in MP-A08'sdrug-like properties (solubility, biodistribution,and potency) hinder its pathway to the clinic. This study demonstratesa liposome-based delivery system of MP-A08 that exhibits enhancedMP-A08 potency against AML cells. MP-A08-liposomes increased MP-A08efficacy against patient AML cells (>140-fold) and significantlyprolongedoverall survival of mice with human AML disease (P = 0.03). The significant antileukemic property of MP-A08-liposomescould be attributed to its enhanced specificity, bioaccessibility,and delivery to the bone marrow, as demonstrated in the pharmacokineticand biodistribution studies. Our findings indicate that MP-A08-liposomeshave potential as a novel treatment for AML.
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