Targeted Heating of Mitochondria Greatly Augments Nanoparticle-Mediated Cancer Chemotherapy.
Targeted Heating of Mitochondria Greatly Augments Nanoparticle-Mediated Cancer Chemotherapy.
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DOI：
10.1002/adhm.202000181
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发表时间：
2020-07
影响因子：
10
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Xu J;Shamul JG;Wang H;Lin J;Agarwal P;Sun M;Lu X;Tkaczuk KHR;He X
癌症是全球第二大死亡原因。各种纳米粒子已经被开发出来，以提高化疗、光热治疗及其组合治疗癌症的有效性和安全性。然而，现有的大多数纳米粒在亚细胞精度和载药量(~lt；≈%)方面都很低，并且亚细胞细胞器的靶向加热对化疗的促进作用还没有得到很好的探讨。在这里，据报道，一种混合的Py@Si-TH纳米颗粒在细胞摄取之前，首先通过其天然配体HA在纳米颗粒最外表面靶向CD44过表达的癌细胞，然后在它们被细胞内摄取后靶向线粒体。此外，该纳米粒子对包裹盐酸阿霉素(DOX)形成Py@Si-TH-DOX纳米粒子具有超高效的作用。在常用的低投料比1：20(DOX：空纳米粒)下包封率为≈100%，在超高投料比1：1时包封率为80%。结合近红外(NIR，808 nm)激光照射，Py@Si-TH-DOX治疗组的肿瘤重量比Py@Si-H-DOX组(即负载DOX的纳米粒无线粒体靶向)小8.5倍，提示靶向加热线粒体是一种有价值的加强化疗抗癌的策略。
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.
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DOI：
10.1085/jgp.201310968
发表时间：
2013-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Calmettes G;John SA;Weiss JN;Ribalet B
通讯作者：
Ribalet B
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
影响因子：
62.1
作者：
Kamaly N;Yameen B;Wu J;Farokhzad OC
通讯作者：
Farokhzad OC
DOI：
10.2174/1874120701105010047
发表时间：
2011
期刊：
The open biomedical engineering journal
影响因子：
--
作者：
He X
通讯作者：
He X
影响因子：
38.3
作者：
Lee, Jae-Hyun;Jang, Jung-tak;Cheon, Jinwoo
通讯作者：
Cheon, Jinwoo