Development of synthetic peptide-modified liposomes with LDL receptor targeting capacity and improved anticancer activity.
作者： Mei Liu , Wei Li , Caroline A. Larregieu , Meng Cheng , Bihan Yan
DOI: 10.1021/MP400759D
关键词:
摘要: In this study, we report an active targeting liposomal formulation directed by a novel peptide (AA13) that specifically binds to the low density lipoprotein receptor (LDLR) overexpressed on acute myeloid leukemia (AML) cells. The objectives of study were evaluate in vitro and vivo tumor drug delivery AA13-anchored liposomes AML AA13 conjugated distal end DSPE-PEG2000-maleimide was incorporated into via postinsertion method. To effect decoration cell internalization cells (THP-1 NB4), stealth bearing 3% (peptide/S100PC, molar ratio, LL) 7% HL) prepared, respectively. Higher uptake LL (1.9- 2.6-fold) HL (2.3- 3.6-fold) targeted occurred THP-1 NB4 cells, respectively, compared untargeted liposomes. An LDLR inhibitor used confirm inhibition receptor-mediated cellular association modified liposome both Daunorubicin (DNR) demonstrated 2.2- 3.5-fold higher cytotoxicity with 1.2- 2.0-fold unmodified Tumor accumulation DNR-loaded greater than biodistribution assay. efficacy BALB/c nude mice xenografts treated DNR loaded also showed more volume longer survival time formulation. conclusion, desirable potential as promising vector for enhanced targeting.
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