Amphiphilic Hybrid Dendritic-Linear Molecules as Nanocarriers for Shape-Dependent Antitumor Drug Delivery,Molecular Pharmaceutics

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Amphiphilic Hybrid Dendritic-Linear Molecules as Nanocarriers for Shape-Dependent Antitumor Drug Delivery
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-05-21 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00190
Yifei Guo ₁ , Ting Wang _{1,

2} , Shuang Zhao ₁ , Meihua Han ₁ , Zhengqi Dong ₁ , Xiangtao Wang ₁ , Yanhong Wang ₂

Affiliation

Nanoparticles based on hybrid block copolymers had been expected as effective nanocarriers for hydrophobic drug delivery. Herein, the novel dendritic-linear molecules from OEG dendron conjugated with octadecylamine (G2-C18) was designed, synthesized, and further applied as nanocarrier to prepare 10-hydroxycamptothecin (HCPT) nanoparticles via antisolvent precipitation method. It seemed that the feed weight ratio of HCPT vs G2-C18 not only affected the drug-loading content of nanoparticles but also influenced the morphology of HCPT nanoparticles; the morphology of HCPT nanoparticles was changed from nanosphere (NSs) to nanorod (NRs) with increasing the feed weight ratio. Both of HCPT nanoparticles presented good stability and similar drug release profiles, but different anticancer efficacy and cellular uptake mechanism. The cytotoxicity of HCPT NRs was enhanced significant comparing with HCPT NSs, the IC₅₀ value was 2-fold lower than HCPT NSs (p < 0.05). More importantly, HCPT NRs showed apparently higher antitumor activity in vivo, the inhibition rate of HCPT NRs was 1.3-fold higher than HCPT NSs. Based on these results, it suggested that the antitumor activity could be influenced significantly by particle morphology, which should be considered and optimized during the nanocarrier design.

中文翻译：

两亲性杂化树突线性分子作为纳米载体的形状依赖的抗肿瘤药物传递。

已经期望基于杂化嵌段共聚物的纳米颗粒作为用于疏水药物递送的有效纳米载体。本文设计，合成了由OEG树枝状分子与十八烷基胺（G2-C18）共轭的新型树枝状线性分子，并进一步用作纳米载体，通过反溶剂沉淀法制备了10-羟基喜树碱（HCPT）纳米粒子。看来HCPT与G2-C18的饲料重量比不仅影响了纳米颗粒的载药量，而且还影响了HCPT纳米颗粒的形貌。随着进料重量比的增加，HCPT纳米颗粒的形态从纳米球（NSs）变为纳米棒（NRs）。HCPT纳米颗粒都表现出良好的稳定性和相似的药物释放曲线，但是具有不同的抗癌功效和细胞摄取机制。与HCPT NSs相比，HCPT NRs的细胞毒性显着增强，IC ₅₀值比HCPT NSs低2倍（p <0.05）。更重要的是，HCPT NRs在体内表现出明显更高的抗肿瘤活性，HCPT NRs的抑制率是HCPT NSs的1.3倍。基于这些结果，表明抗肿瘤活性可能受到颗粒形态的显着影响，在纳米载体设计过程中应予以考虑和优化。

更新日期：2018-05-21

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