The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.
The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.
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作者：
将药物包封在纳米载体中，选择性地靶向恶性细胞，有望减轻传统化疗的副作用，并使个性化医疗所需的独特药物组合得以传递。然而，为了实现这一潜力，靶向纳米载体必须同时克服多种挑战，包括特异性、稳定性和对不同货物的高容量。在这里，我们报道了多孔纳米颗粒支持的脂质双层（原细胞），它协同结合了脂质体和纳米多孔颗粒的特性。与肝细胞、内皮细胞和免疫细胞相比，用靶向肽修饰的原细胞对人肝细胞癌（HCC）的亲和力高10000倍。此外，原始细胞可以装载治疗（药物、siRNA和毒素）和诊断（量子点）制剂的组合，并进行修饰以促进内体逃逸和选定货物的核积累。高表面积纳米孔核的巨大容量与液体支持的脂质双分子层增强的靶向效力相结合，使单个携带药物混合物的原始细胞能够杀死耐药的HCC细胞，比同类脂质体提高了106倍。
Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability, and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma (HCC) exhibit a 10,000-fold greater affinity for HCC than for hepatocytes, endothelial cells, and immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, siRNA, and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposomes.
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影响因子：
3.9
作者：
Carroll, Nick J.;Pylypenko, Svitlana;Petsev, Dimiter N.
通讯作者：
Petsev, Dimiter N.
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
影响因子：
10.8
作者：
Huang, Shih-Chieh J.;Artyukhin, Alexander B.;Noy, Aleksandr
通讯作者：
Noy, Aleksandr
DOI：
10.1016/0005-2736(93)90398-j
发表时间：
1993-12-12
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ELORZA, B;ELORZA, MA;CHANTRES, JR
通讯作者：
CHANTRES, JR
影响因子：
4.8
作者：
Khalil, IA;Kogure, K;Harashima, H
通讯作者：
Harashima, H