Combination therapy has emerged as an efficient way to deliver chemotherapeutics for treatment of glioblastoma. It provides collaborative approach of targeting cancer cells by acting via multiple mechanisms, thereby reducing drug resistance. However, the presence of impermeable blood brain barrier (BBB) restricts the delivery of chemotherapeutic drugs into the brain. To overcome this limitation, we designed a dual functionalized liposomes by modifying their surface with transferrin (Tf) and a cell penetrating peptide (CPP) for receptor and adsorptive mediated transcytosis, respectively. In this study, we used two different CPPs (based on physicochemical properties) and investigated the influence of insertion of CPP to Tf-liposomes on biocompatibility, cellular uptake, and transport across the BBB both in vitro and in vivo. The biodistribution profile of Tf-CPP liposomes showed more than 10 and 2.7 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively as compared to free drugs with no signs of toxicity.

中文翻译：

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TAT或QLPVM的生物分布与受体靶向脂质体偶联，可在体外和体内将抗癌治疗药物递送至大脑。

组合疗法已成为提供化学疗法治疗胶质母细胞瘤的有效方法。它提供了通过多种机制发挥作用来靶向癌细胞的协作方法，从而降低了耐药性。但是，不可渗透的血脑屏障（BBB）的存在限制了化疗药物向大脑的输送。为了克服这一限制，我们设计了一种双重功能化脂质体，分别通过转铁蛋白（Tf）和细胞穿透肽（CPP）修饰其表面，以分别用于受体介导和吸附介导的胞吞作用。在这项研究中，我们使用了两种不同的CPP（基于理化性质），并研究了将CPP插入Tf-脂质体对生物相容性，细胞摄取以及在体内和体外通过BBB转运的影响。