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载紫杉醇的 HSA-血晶素纳米粒肿瘤靶向递药用于癌症治疗。

Tumor-specific delivery of a paclitaxel-loading HSA-haemin nanoparticle for cancer treatment.

机构信息

Department of Biomedical Sciences and Institute for Medical Science, Chonbuk National University Medical School, Jeonju, Chonbuk, South Korea.

JINIS BDRD institute, JINIS Biopharmaceuticals Co., Wanju, Chonbuk, South Korea.

出版信息

Nanomedicine. 2020 Jan;23:102089. doi: 10.1016/j.nano.2019.102089. Epub 2019 Sep 2.

Abstract

A cancer-targeted chemotherapy could potentially eradicate cancers if anticancer drugs are delivered precisely to the cancers. Although various types of nanoparticles have been developed for cancer-specific delivery of anticancer drugs, the drug delivery capabilities of these nanoparticles were not specific enough to eradicate cancer. Here, we developed a targeting-enhancing nanoparticle of paclitaxel, in which paclitaxel was encapsulated with a human serum albumin-haemin complex through non-covalent bonding. The average diameter of TENPA was approximately 140 nm with a zeta potential of +29 mV. TENPA maintained its structural integrity and stability without forming protein coronas in the blood for optimal passive targeting. These characteristics of TENPA resulted in paclitaxel accumulation that was 4.1 times greater than that of Abraxane, an albumin-bound paclitaxel, in cancer tissue. The dramatic improvement in cancer targeting of TENPA led to reduced systemic toxicity of paclitaxel and eradication of end-stage cancer in a xenografted mouse experiment.

摘要

一种针对癌症的化疗方法,如果抗癌药物能精确地输送到癌症部位,就有可能消灭癌症。虽然已经开发出了各种类型的纳米颗粒来专门输送抗癌药物,但这些纳米颗粒的药物输送能力还不够精确,无法消灭癌症。在这里,我们开发了一种紫杉醇靶向增强型纳米粒子,它通过非共价键将紫杉醇包裹在人血清白蛋白-血红素复合物中。TENPA 的平均直径约为 140nm,zeta 电位为+29mV。TENPA 在血液中保持其结构完整性和稳定性,不会形成蛋白质冠,从而实现最佳的被动靶向。TENPA 的这些特性导致紫杉醇在肿瘤组织中的积累量是白蛋白结合紫杉醇 Abraxane 的 4.1 倍。TENPA 对癌症靶向性的显著改善导致紫杉醇的全身毒性降低,并在异种移植小鼠实验中消除了晚期癌症。

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