Xu Jiangsheng, Shamul James G, Wang Hai, Lin John, Agarwal Pranay, Sun Mingrui, Lu Xiongbin, Tkaczuk Katherine H R, He Xiaoming
Fishell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Department of Biomedical Engineering, The Ohio State University, Columbus, OH, 43210, USA.
Adv Healthc Mater. 2020 Jul;9(14):e2000181. doi: 10.1002/adhm.202000181. Epub 2020 Jun 17.
Cancer is the second leading cause of mortality globally. Various nanoparticles have been developed to improve the efficacy and safety of chemotherapy, photothermal therapy, and their combination for treating cancer. However, most of the existing nanoparticles are low in both subcellular precision and drug loading content (<≈5%), and the effect of targeted heating of subcellular organelles on the enhancement of chemotherapy has not been well explored. Here, a hybrid Py@Si-TH nanoparticle is reported to first target cancer cells overexpressed with the variant CD44 via its natural ligand HA on the outermost surface of the nanoparticle before cellular uptake, and then target mitochondria after they are taken up inside cells. In addition, the nanoparticle is ultraefficient for encapsulating doxorubicin hydrochloride (DOX) to form Py@Si-TH-DOX nanoparticle. The encapsulation efficiency is ≈100% at the commonly used low feeding ratio of 1:20 (DOX:empty nanoparticle), and >80% at an ultrahigh feeding ratio of 1:1. In combination with near infrared (NIR, 808 nm) laser irradiation, the tumor weight in the Py@Si-TH-DOX treatment group is 8.5 times less than that in the Py@Si-H-DOX (i.e., DOX-laden nanoparticles without mitochondrial targeting) group, suggesting targeted heating of mitochondria is a valuable strategy for enhancing chemotherapy to combat cancer.
癌症是全球第二大死亡原因。人们已开发出各种纳米颗粒，以提高化疗、光热疗法及其联合治疗癌症的疗效和安全性。然而，现有的大多数纳米颗粒在亚细胞精度和药物负载量（<≈5%）方面都较低，并且亚细胞器靶向加热对增强化疗效果的作用尚未得到充分探索。在此，报道了一种杂化的Py@Si-TH纳米颗粒，它在细胞摄取前通过纳米颗粒最外层的天然配体HA首先靶向过表达变体CD44的癌细胞，然后在被细胞摄取后靶向线粒体。此外，该纳米颗粒对封装盐酸多柔比星（DOX）形成Py@Si-TH-DOX纳米颗粒具有超高效率。在常用的1:20（DOX:空纳米颗粒）低投料比下，封装效率约为100%，在1:1的超高投料比下大于80%。与近红外（NIR，波长808nm）激光照射相结合，Py@Si-TH-DOX治疗组的肿瘤重量比Py@Si-H-DOX（即不含线粒体靶向的载DOX纳米颗粒）组轻8.5倍，这表明线粒体靶向加热是增强化疗以对抗癌症的一种有价值的策略。
