Adenovirus-Derived Nano-Capsid Platforms for Targeted Delivery and Penetration of Macromolecules into Resistant and Metastatic Tumors.
Adenovirus-Derived Nano-Capsid Platforms for Targeted Delivery and Penetration of Macromolecules into Resistant and Metastatic Tumors.
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许多癌症治疗剂可能对靶分子具有稳健的作用，但缺乏有效定位到肿瘤细胞中的手段，因此显示出降低的治疗功效。病毒具有自然进化的机制，以确保核酸货物进入细胞并定位。利用和更好地理解有助于腺病毒细胞进入机制的五邻体基础蛋白的机制可以改善肿瘤靶向治疗剂的细胞内递送。这篇综述描述了五酮基衍生的癌症纳米细胞的发展，并强调了强大的交付到肿瘤细胞的基本要求。核酸、肽和蛋白质等大分子治疗剂有可能克服癌症的治疗障碍。例如，核酸或肽生物制剂可以提供用于攻击原本不可治疗的治疗靶标（诸如转录因子和类似的肿瘤驱动因子）的替代策略。将生物治疗剂递送到肿瘤细胞中需要强大的细胞穿透系统以接近细胞内部的治疗靶标。一种非常有效的方法可以从穿透细胞的病原体（如病毒）中借鉴。特别地，腺病毒五邻体基础衣壳蛋白的细胞进入功能在穿透肿瘤细胞以用于大分子疗法和膜不可渗透药物的细胞内沉积方面是有效的。在这里，我们提供了一个概述，描述肿瘤靶向五邻体基衍生的纳米衣壳的演变作为一个框架，讨论克服大分子传递的关键障碍的要求。这些蛋白质用于治疗递送的开发和临床前测试也开始揭示五邻体基底的膜穿透功能的难以捉摸的机制。对这一机制的理解可能会释放大分子治疗剂被有效递送到癌细胞中的潜力，并为抵抗当前临床治疗的肿瘤提供治疗选择。
Many cancer therapeutics may have a robust effect on target molecules but lack the means of effective localization into tumor cells, thus displaying reduced therapeutic efficacy. Viruses bear naturally evolved machinery to ensure entry and localization of nucleic acid cargo into a cell. Utilizing and better understanding the mechanism of the penton base protein that contributes to the adenovirus cell entry machinery may improve the intracellular delivery of tumor targeting therapeutics. This review describes the progression of penton-base-derived cancer nanotherapeutic development and highlights essential requirements for robust delivery into a tumor cell. Macromolecular therapeutics such as nucleic acids, peptides, and proteins have the potential to overcome treatment barriers for cancer. For example, nucleic acid or peptide biologics may offer an alternative strategy for attacking otherwise undruggable therapeutic targets such as transcription factors and similar oncologic drivers. Delivery of biological therapeutics into tumor cells requires a robust system of cell penetration to access therapeutic targets within the cell interior. A highly effective means of accomplishing this may be borrowed from cell-penetrating pathogens such as viruses. In particular, the cell entry function of the adenovirus penton base capsid protein has been effective at penetrating tumor cells for the intracellular deposition of macromolecular therapies and membrane-impermeable drugs. Here, we provide an overview describing the evolution of tumor-targeted penton-base-derived nano-capsids as a framework for discussing the requirements for overcoming key barriers to macromolecular delivery. The development and pre-clinical testing of these proteins for therapeutic delivery has begun to also uncover the elusive mechanism underlying the membrane-penetrating function of the penton base. An understanding of this mechanism may unlock the potential for macromolecular therapeutics to be effectively delivered into cancer cells and to provide a treatment option for tumors resisting current clinical therapies.
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DOI：
10.1186/s13046-017-0667-1
发表时间：
2018-02-06
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Chalouni C;Doll S
通讯作者：
Doll S
影响因子：
4.8
作者：
Clark, Paul A.;Iida, Mari;Kuo, John S.
通讯作者：
Kuo, John S.
影响因子：
8.9
作者：
Akkilic, Namik;Liljeblad, Mathias;Geschwindner, Stefan
通讯作者：
Geschwindner, Stefan
DOI：
10.1016/j.jconrel.2017.12.024
发表时间：
2018-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Sims JD;Taguiam JM;Alonso-Valenteen F;Markman J;Agadjanian H;Chu D;Lubow J;Abrol R;Srinivas D;Jain A;Han B;Qu Y;Mirzadehgan P;Hwang JY;Rentsendorj A;Chung A;Lester J;Karlan BY;Gray HB;Gross Z;Giuliano A;Cui X;Medina-Kauwe LK
通讯作者：
Medina-Kauwe LK
影响因子：
5.1
作者：
Alba, R;Bosch, A;Chillon, M
通讯作者：
Chillon, M