Nanoassemblies from amphiphilic cytarabine prodrug for leukemia targeted therapy

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• 作者：Jing Liu^a ; Dujuan Zhao^a ; Wenxiu He^a ; Huiyuan Zhang^a ; Zhonghao Li^b ; Yuxia Luan^a ; ^{yuxialuan@sdu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cytarabine ; Amphiphilic small molecular prodrug ; Nanoassembly ; Folic acid ; Leukemia therapy
• 刊名：Journal of Colloid and Interface Science
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：487
• 期：Complete
• 页码：239-249
• 全文大小：3086 K

文摘

The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH₂ of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71 wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared. The results of MTT assays on FR-positive K562 cells and FR-negative A549 cells demonstrated higher cytotoxicity of HA-Ara NAs than the native drug. Especially, the IC₅₀ values revealed that NAs/FA-BSA was 3 and 2-fold effective than non-targeted NAs after 24 and 48 h treatment with K562 cells, respectively indicating FR-mediated enhanced anti-tumor efficacy. In vitro cellular uptake, larger accumulation of HA-Ara NAs were observed in comparative with the free FITC and the results further confirmed the selective uptake of NAs/FA-BSA in folate receptor enriched cancer cells. Above all, self-assembled HA-Ara NAs exhibited potential superiority for Ara-C delivery and FA-modified NAs would be an excellent candidate for targeting leukemia therapy.