Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer.
Enhanced in vitro and in vivo therapeutic efficacy of codrug-loaded nanoparticles against liver cancer.
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增强共药纳米粒子对肝癌的体外和体内治疗功效
DOI：
10.2147/ijn.s34886
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发表时间：
2012
影响因子：
8
通讯作者：
Lu X
中科院分区：
文献类型：
--
作者：
Li X;Xu H;Dai X;Zhu Z;Liu B;Lu X
紫杉醇（Ptx）是目前应用最广泛的抗癌药物之一，对多种实体瘤有显著的抑制作用。然而，Ptx的治疗反应通常与其非特异性细胞毒性作用和特殊溶剂（Cremophor EL®）引起的严重副作用有关。本文报道了两亲性甲氧基聚乙二醇-聚己内酯嵌段共聚物对Ptx/粉防己碱（泰特）共载纳米粒的稳定控释作用。有三个重要的发现。首先，泰特可以有效地稳定载铂纳米粒与泰特和Ptx的共封装。还探讨了不同Ptx/泰特进料比对纳米颗粒的尺寸和负载效率的影响。第二，将泰特和Ptx包裹到纳米粒中保留了泰特和Ptx对小鼠肝癌H22细胞的协同抗癌效率。第三，在体内评价中，采用瘤内给药以增加位点特异性递送。Ptx/泰特纳米颗粒，当在肿瘤内递送时，表现出显著改善的抗肿瘤功效;此外，它们在建立的H22移植小鼠模型中显著增加了总体存活率。作为正在进行的研究的一部分，正在积极考虑进一步研究这种纳米递送系统的抗癌机制。结果表明，Ptx/Tet-coloaded纳米粒子可能是一个潜在的有用的化疗制剂用于肝癌治疗。
Paclitaxel (Ptx), one of the most widely used anticancer agents, has demonstrated extraordinary activities against a variety of solid tumors. However, the therapeutic response of Ptx is often associated with severe side effects caused by its nonspecific cytotoxic effects and special solvents (Cremophor EL®). The current study reports the stable controlled release of Ptx/tetrandrine (Tet)-coloaded nanoparticles by amphilic methoxy poly(ethylene glycol)–poly(caprolactone) block copolymers. There were three significant findings. Firstly, Tet could effectively stabilize Ptx-loaded nanoparticles with the coencapsulation of Tet and Ptx. The influence of different Ptx/Tet feeding ratios on the size and loading efficiency of the nanoparticles was also explored. Secondly, the encapsulation of Tet and Ptx into nanoparticles retains the synergistic anticancer efficiency of Tet and Ptx against mice hepatoma H22 cells. Thirdly, in the in vivo evaluation, intratumoral administration was adopted to increase the site-specific delivery. Ptx/Tet nanoparticles, when delivered intratumorally, exhibited significantly improved antitumor efficacy; moreover, they substantially increased the overall survival in an established H22-transplanted mice model. Further investigation into the anticancer mechanisms of this nanodelivery system is under active consideration as a part of this ongoing research. The results suggest that Ptx/Tet-coloaded nanoparticles could be a potential useful chemotherapeutic formulation for liver cancer therapy.