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首页> 外文期刊>Biomaterials Science >Anti-angiogenic nanotherapy via active targeting systems to tumors and adipose tissue vasculature
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Anti-angiogenic nanotherapy via active targeting systems to tumors and adipose tissue vasculature

机译：通过针对肿瘤和脂肪组织脉管的主动靶向系统进行抗血管生成纳米疗法

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摘要

Sophisticated drug delivery systems (DDS) are required for delivering drugs, especially macromolecules such as nucleic acids or proteins, to their sites of action. Therefore it is a prerequisite that future DDS are designed to selectively target a tissue. In this review, we focus on systems that actively target the vasculature in tumors or adipose tissues. For targeting tumor vasculatur, a new strategy referred to as dual-targeting is proposed that uses a combination of a receptor specific ligand and a cell penetrating peptide, which can induce the synergistic enhancement of tissue selectivity under in vivo conditions. A novel pH-sensitive cationic lipid was designed to enhance the endosomal release of encapsulated compounds such as siRNA as well as to improve the stability in blood circulation after intravenous administration. A cyclic RGD peptide is used as an active targeting ligand. For targeting adipose vasculature, prohibitin, which is expressed on the surface of adipose endothelial cells, was targeted with KGGRAKD peptides on the surface of PEGylated nanoparticles. Prohibitin targeted nanoparticles (PTNP) encapsulating Cytochrome c (CytC) can selectively target adipose vasculature by optimizing the lengths of the PEG linkers and can deliver CytC to adipose endothelial cells. PTNP can successfully induce anti-obese effects as well as apoptosis by delivering CytC to the cytosol in endothelial cells. Unexpectedly, the EPR (enhanced permeability and retention) effect, which is usually observed in tumor tissue, was also observed in the adipose vasculature, especially in obese mice, where PEGylated nanoparticles can pass through the endothelial barriers in adipose tissue. We believe that these achievements in active targeting will allow a greatly expanded use of DDS for nanomedicines.
机译：需要复杂的药物输送系统（DDS）将药物，尤其是大分子，例如核酸或蛋白质，输送到其作用部位。因此，将未来的DDS设计为选择性靶向组织的前提。在这篇综述中，我们关注于主动靶向肿瘤或脂肪组织中脉管系统的系统。为了靶向肿瘤血管，提出了一种新的策略，称为双重靶向，其使用受体特异性配体和细胞穿透肽的组合，其可以在体内条件下诱导组织选择性的协同增强。设计了一种新型的pH敏感型阳离子脂质，以增强胶囊化化合物（如siRNA）的内体释放，并改善静脉内给药后血液循环的稳定性。环状RGD肽用作活性靶向配体。为了靶向脂肪脉管系统，将在脂肪内皮细胞表面表达的禁止素与聚乙二醇化纳米颗粒表面的KGGRAKD肽靶向。包封细胞色素c（CytC）的抑制素靶向纳米颗粒（PTNP）可以通过优化PEG接头的长度选择性地靶向脂肪脉管系统，并且可以将CytC递送至脂肪内皮细胞。 PTNP通过将CytC传递到内皮细胞的细胞质中，可以成功地诱导抗肥胖作用以及凋亡。出乎意料的是，通常在肿瘤组织中也观察到的EPR（增强的通透性和滞留性）效应也在脂肪脉管系统中观察到，特别是在肥胖小鼠中，其中聚乙二醇化的纳米颗粒可以穿过脂肪组织中的内皮屏障。我们相信，在主动靶向方面的这些成就将使DDS在纳米药物中的应用大大扩展。

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