前药
紫杉醇
细胞毒性
药理学
药物输送
靶向给药
阿霉素
组织蛋白酶B
治疗指标
体内
乳腺癌
纳米载体
靶向治疗
药品
毒性
材料科学
癌症研究
癌细胞
癌症
毒品携带者
癌症治疗
医学
体外
脂质体
光热治疗
化学
纳米技术
内科学
生物化学
酶
作者
Arpan Satsangi,Sudipa Saha Roy,Rajiv K. Satsangi,Anthony W. Tolcher,Ratna K. Vadlamudi,Beth A. Goins,Joo L. Ong
出处
期刊:Biomaterials
[Elsevier]
日期:2015-08-01
卷期号:59: 88-101
被引量:54
标识
DOI:10.1016/j.biomaterials.2015.03.039
摘要
Breast cancer is the leading cause of cancer deaths among women. Paclitaxel (PTX), an important breast cancer medicine, exhibits reduced bioavailability and therapeutic index due to high hydrophobicity and indiscriminate cytotoxicity. PTX encapsulation in one-level active targeting overcomes such barriers, but enhances toxicity to normal tissues with cancer-similar expression profiles. This research attempted to overcome this challenge by increasing selectivity of cancer cell targeting while maintaining an ability to overcome traditional pharmacological barriers. Thus, a multi-core, multi-targeting construct for tumor specific delivery of PTX was fabricated with (i) an inner-core prodrug targeting the cancer-overexpressed cathepsin B through a cathepsin B-cleavable tetrapeptide that conjugates PTX to a poly(amidoamine) dendrimer, and (ii) the encapsulation of this prodrug (PGD) in an outer core of a RES-evading, folate receptor (FR)-targeting liposome. Compared to traditional FR-targeting PTX liposomes, this sequentially active-targeted dendrosome demonstrated better prodrug retention, an increased cytotoxicity to cancer cells (latter being true when FR and cathepsin B activities were both at moderate-to-high levels) and higher tumor reduction. This research may eventually evolve a product platform with reduced systemic toxicity inherent with traditional chemotherapy and localized toxicity inherent to single-target nanoplatforms, thereby allowing for better tolerance of higher therapeutic load in advanced disease states.
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