Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates
Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle-aptamer bioconjugates
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DOI：
10.1002/cmdc.200700121
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发表时间：
2007-09-01
期刊：
影响因子：
3.4
通讯作者：
Farokhzad, Omid C.
中科院分区：
文献类型：
--
作者：
Zhang, Liangfang;Radovic-Moreno, Aleksandar F.;Farokhzad, Omid C.
在过去的二十年中，已经出现了许多纳米颗粒（NP）药物递送载体，包括例如聚合物NP、嵌段共聚物胶束、脂质体、树枝状聚合物和水凝胶，其中许多已经被工程化用于改善血清稳定性、生物相容性和体内循环时间。[1-4]纳米颗粒药物递送系统的一个有前途的应用是以细胞、组织或疾病特异性方式靶向递送治疗剂。该目标可以通过用抗体、核酸配体（适体; Apt）、肽或结合靶细胞或组织上存在的抗原的小分子对NP进行表面修饰来实现。[5，6] NP的另一个有前景的应用可能是使用相同的NP递送装置共同递送不同的药物。与递送单一药物相比，多种药物的共递送具有几个潜在的优势，包括：1）协同效应[7] 2）抑制耐药性[8]和3）将各种药物的相对剂量调整到单个NP载体水平的能力。脂质体和阳离子核壳NP已经被开发用于同时将药物和DNA质粒递送到细胞。[9，10]最近，还描述了一种新的多功能系统，其包含包埋在脂质体内的聚合物NP，其可以以时间方式递送两种亲水性药物。[11]工程化多功能纳米颗粒的一个主要挑战是保持设计的简单性以确保未来的规模扩大，同时结合所需的功能，如靶向递送，时间调节的药物释放，以及同时递送不同药物的能力。逻辑-
Numerous nanoparticle (NP) drug delivery vehicles have emerged during the past two decades including, for example, polymeric NPs, block copolymer micelles, liposomes, dendrimers, and hydrogels, many of which have been engineered for improved serum stability, biocompatibility, and in vivo circulation time.[1–4] A promising application of nanoparticle (NP) drug delivery systems is the targeted delivery of therapeutic agents in a cell-, tissue-, or disease-specific manner. This goal may be achieved by the surface-modification of NPs with antibodies, nucleic acid ligands (aptamers; Apt), peptides, or small molecules that bind to antigens present on the target cells or tissues.[5, 6] Another promising application of NPs may be the codelivery of different drugs using the same NP delivery device. Compared to delivering a single drug, co-delivery of multiple drugs has several potential advantages, including: 1) synergistic effects,[7] 2) suppressed drug resistance,[8] and 3) the ability to tune the relative dosage of various drugs to the level of a single NP carrier.Liposomes and cationic core-shell NP have been developed to simultaneously deliver drugs and DNA plasmids to cells.[9, 10] More recently, a novel multifunctional system comprising of polymeric NPs entrapped within liposomes has also been described that can deliver two hydrophilic drugs in a temporal manner.[11] One major challenge in engineering multifunctional nanoparticles is maintaining the simplicity in design to assure future scale-up, while incorporating the desired functionalities such as targeted delivery, temporally regulated drug release, and the ability to simultaneously deliver distinct drugs. A logi-