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Transferrin-binding peptide functionalized polymersomes mediate targeted doxorubicin delivery to colorectal cancer in vivo.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.jconrel.2020.01.012 Yaohua Wei 1 , Xiaolei Gu 2 , Yinping Sun 2 , Fenghua Meng 2 , Gert Storm 3 , Zhiyuan Zhong 2
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.jconrel.2020.01.012 Yaohua Wei 1 , Xiaolei Gu 2 , Yinping Sun 2 , Fenghua Meng 2 , Gert Storm 3 , Zhiyuan Zhong 2
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Transferrin receptor (TfR) is a promising target validated in the clinical trials for managing various malignancies. Transferrin (Tf) and single chain antibody fragment can target TfR and are typically conjugated to nanomedicines via post-modification, which poses significant production challenges. Here, we report that the polymersomes functionalized with a Tf-binding peptide CGGGHKYLRW (TBP-Ps) can selectively and stably bind Tf and subsequently mediate targeted doxorubicin (Dox) delivery to TfR over-expressing HCT-116 colorectal cancer cells in vitro and in vivo. The Tf surface density of the polymersomes could be controlled by the surface content of TBP. Interestingly, modifying Dox-loaded TBP-Ps with Tf led to greatly increased cellular uptake and inhibitory effect of HCT-116 cells. Tf-bound TBP-Ps demonstrated rapid accumulation in the tumor xenografts in nude mice following i.v. injection. More importantly, Dox-loaded Ps with Tf binding significantly enhanced the antitumor efficacy in mice bearing HCT-116 tumors compared to polymersomes without Tf binding. Surface functionalization of the nanoparticles with Tf-binding peptide provides an appealing strategy in formulating Tf-targeted nanomedicines.
中文翻译：
转铁蛋白结合肽功能化的聚合物小体在体内介导靶向阿霉素递送至结肠直肠癌。
转铁蛋白受体（TfR）是在临床试验中验证的用于治疗各种恶性肿瘤的有希望的靶标。转铁蛋白（Tf）和单链抗体片段可以靶向TfR，通常通过后修饰与纳米药物偶联，这给生产带来了巨大挑战。在这里，我们报道用Tf结合肽CGGGHKYLRW（TBP-Ps）功能化的聚合物囊泡可以选择性和稳定地结合Tf，随后介导靶向阿霉素（Dox）递送至在体外和体内过量表达TCT的HCT-116结直肠癌细胞体内。聚合物囊泡的Tf表面密度可以通过TBP的表面含量来控制。有趣的是，用Tf修饰载有Dox的TBP-Ps可以大大提高细胞摄取和HCT-116细胞的抑制作用。静脉注射后，结合Tf的TBP-Ps在裸鼠的肿瘤异种移植物中显示出快速积累。更重要的是，与没有Tf结合的聚合物囊泡相比，带有Tf结合的Dox加载的Ps显着增强了携带HCT-116肿瘤的小鼠的抗肿瘤功效。具有Tf结合肽的纳米颗粒的表面功能化为配制Tf靶向的纳米药物提供了一种有吸引力的策略。
更新日期：2020-01-07
中文翻译：
转铁蛋白结合肽功能化的聚合物小体在体内介导靶向阿霉素递送至结肠直肠癌。
转铁蛋白受体（TfR）是在临床试验中验证的用于治疗各种恶性肿瘤的有希望的靶标。转铁蛋白（Tf）和单链抗体片段可以靶向TfR，通常通过后修饰与纳米药物偶联，这给生产带来了巨大挑战。在这里，我们报道用Tf结合肽CGGGHKYLRW（TBP-Ps）功能化的聚合物囊泡可以选择性和稳定地结合Tf，随后介导靶向阿霉素（Dox）递送至在体外和体内过量表达TCT的HCT-116结直肠癌细胞体内。聚合物囊泡的Tf表面密度可以通过TBP的表面含量来控制。有趣的是，用Tf修饰载有Dox的TBP-Ps可以大大提高细胞摄取和HCT-116细胞的抑制作用。静脉注射后，结合Tf的TBP-Ps在裸鼠的肿瘤异种移植物中显示出快速积累。更重要的是，与没有Tf结合的聚合物囊泡相比，带有Tf结合的Dox加载的Ps显着增强了携带HCT-116肿瘤的小鼠的抗肿瘤功效。具有Tf结合肽的纳米颗粒的表面功能化为配制Tf靶向的纳米药物提供了一种有吸引力的策略。
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