Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy.
Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy.
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DOI：
10.1016/j.canlet.2017.09.043
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发表时间：
2018-02-01
期刊：
影响因子：
9.7
通讯作者：
Guo P
中科院分区：
文献类型：
--
作者：
Xu C;Haque F;Jasinski DL;Binzel DW;Shu D;Guo P
在过去的几十年里，一些纳米技术平台成功地过渡到临床试验。然而，治疗药物对肿瘤的特异性递送受到几个障碍的阻碍，包括癌症识别和组织渗透；颗粒非均质性和聚集性；不利的药代动力学特征，如快速清除和器官积累。随着RNA纳米技术的出现，一系列RNA纳米颗粒已被成功构建，以克服上述许多挑战，以良好的生物分布特征在体内靶向癌症。与其他纳米递送平台相比，RNA纳米颗粒的物理化学性质可以相对容易地调整，以研究全身注射后纳米颗粒的体内行为。RNA纳米颗粒的大小、形状和表面化学性质，尤其是疏水修饰，对其在体内的命运有着重要的影响。合理设计的RNA纳米颗粒具有明确的化学计量和高均匀性，经全身注射后可特异性靶向肿瘤细胞，同时避免在健康重要器官中积累。在一些动物模型中，RNA纳米颗粒被证明可以提供治疗药物，如siRNA和抗mirna，以阻止肿瘤生长。虽然RNA纳米颗粒释放抗mirna在多个动物模型中实现了肿瘤消退的高效率，但内体逃逸siRNA递送的效率有待进一步提高。本文综述了RNA纳米技术在癌症靶向和治疗方面的研究进展和前景。
The past decades have witnessed the successful transition of several nanotechnology platforms into the clinical trials. However, specific delivery of therapeutics to tumors is hindered by several barriers including cancer recognition and tissue penetration; particle heterogeneity and aggregation; unfavorable pharmacokinetic profiles such as fast clearance and organ accumulation. With the advent of RNA nanotechnology, a series of RNA nanoparticles have been successfully constructed to overcome many of the aforementioned challenges for in vivo cancer targeting with favorable biodistribution profiles. Compared to other nanodelivery platforms, the physiochemical properties of RNA nanoparticles can be tuned with relative ease for investigating the in vivo behavior of nanoparticles upon systemic injection. The size, shape, and surface chemistry, especially hydrophobic modifications, exert significant impacts on the in vivo fate of RNA nanoparticles. Rationally designed RNA nanoparticles with defined stoichiometry and high homogeneity have been demonstrated to specifically target tumor cells while avoiding accumulation in healthy vital organs after systemic injection. RNA nanoparticles were proven to deliver therapeutics such as siRNA and anti-miRNA to block tumor growth in several animal models. Although the release of anti-miRNA from the RNA nanoparticles has achieved high efficiency of tumor regression in multiple animal models, the efficiency of endosomal escape for siRNA delivery needs further improvement. This review focuses on the advances and perspectives of this promising RNA nanotechnology platform for cancer targeting and therapy.
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影响因子：
17.1
作者：
Anchordoquy TJ;Barenholz Y;Boraschi D;Chorny M;Decuzzi P;Dobrovolskaia MA;Farhangrazi ZS;Farrell D;Gabizon A;Ghandehari H;Godin B;La-Beck NM;Ljubimova J;Moghimi SM;Pagliaro L;Park JH;Peer D;Ruoslahti E;Serkova NJ;Simberg D
通讯作者：
Simberg D
影响因子：
56.9
作者：
Chworos, A;Severcan, I;Jaeger, L
通讯作者：
Jaeger, L
影响因子：
4.5
作者：
Binzel, Daniel W.;Khisamutdinov, Emil;Guo, Peixuan
通讯作者：
Guo, Peixuan
影响因子：
14.9
作者：
Busch A;Backofen R
通讯作者：
Backofen R
影响因子：
12.4
作者：
Abdelmawla, Sherine;Guo, Songchuan;Li, Qi-Xiang
通讯作者：
Li, Qi-Xiang