pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery.
pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery.
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DOI：
10.1038/srep37891
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发表时间：
2016-11-24
影响因子：
4.6
通讯作者：
Tan WS
中科院分区：
文献类型：
--
作者：
Biabanikhankahdani R;Alitheen NBM;Ho KL;Tan WS
具有特异性靶向部分和pH响应特性的多功能纳米载体为靶向癌症治疗提供了巨大的潜力。几种合成药物载体作为药物递送系统已被广泛研究，但关于病毒样纳米颗粒（VLNP）作为多功能纳米载体的应用的信息不多。在这里，我们描述了pH响应VLNP的发展，截短的B病毒核心抗原（tHBcAg）的基础上，显示叶酸（FA）的控制药物输送。将FA与结合在tHBcAg纳米颗粒上的含有十五肽的纳米胶缀合，以增加药物递送系统的特异性和功效。负载有阿霉素（DOX）和聚丙烯酸（PAA）的tHBcAg纳米颗粒在肿瘤组织条件下以受控的方式在体外表现出持续的药物释放曲线，并改善了结肠直肠癌细胞对DOX的摄取，从而增强了抗肿瘤作用。该研究表明，DOX-PAA可以被包装到VLNP中而不对DOX分子进行任何修饰，从而保留了负载的DOX的药理活性。纳米胶水可以很容易地用于在VLNP的外表面上展示肿瘤靶向分子，并且可以绕过费力和耗时的基因工程方法。
Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
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