Co-delivery of gambogic acid and TRAIL plasmid by hyaluronic acid grafted PEI-PLGA nanoparticles for the treatment of triple negative breast cancer.
Co-delivery of gambogic acid and TRAIL plasmid by hyaluronic acid grafted PEI-PLGA nanoparticles for the treatment of triple negative breast cancer.
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透明质酸接枝 PEI-PLGA 纳米颗粒共同递送藤黄酸和 TRAIL 质粒用于治疗三阴性乳腺癌。
DOI：
10.1080/10717544.2017.1406558
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发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Wang S;Shao M;Zhong Z;Wang A;Cao J;Lu Y;Wang Y;Zhang J
基于肿瘤坏死因子相关凋亡诱导配体（Tumor necrosis factor-related apoptosis-inducing ligand， TRAIL）的联合治疗和基因治疗是克服TRAIL局限性的新策略，但缺乏高效、低毒的载体仍然是主要障碍。在这项研究中，我们开发了一种透明质酸（HA）修饰的聚乙烯亚胺-聚（d，l-丙交酯-共乙醇酸）（PEI-PLGA）纳米颗粒（NP）系统，用于靶向共递送TRAIL质粒（pTRAIL）和甘草酸（GA）治疗三阴性乳腺癌（TNBC）。GA被封装在PEI-PLGA NPs的核心，pTRAIL通过电荷吸附吸附在正NP表面。HA包被PEI-PLGA NPs作为靶向配体，与TNBC细胞的CD44受体结合，并形成一个外壳来中和内部NPs的多余正电荷。由此得到的pTRAIL和GA共负载ha包被的PEI-PLGA NPs呈球形（121.5 nm），可以通过cd44依赖的内吞途径促进负载的货物内化进入TNBC细胞。双重载药NPs在体外显著增加凋亡细胞死亡，在体内抑制TNBC肿瘤生长。这种多功能NP系统有效地联合递送GA和pTRAIL，因此代表了一种治疗TNBC的有希望的策略，并为TNBC联合治疗中治疗性DNA和化疗药物的联合递送提供了平台策略。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based combination therapy and gene therapy are new strategies to potentially overcome the limitations of TRAIL, however, the lack of efficient and low toxic vectors remains the major obstacle. In this study, we developed a hyaluronic acid (HA)-decorated polyethylenimine-poly(d,l-lactide-co-glycolide) (PEI-PLGA) nanoparticle (NP) system for targeted co-delivery of TRAIL plasmid (pTRAIL) and gambogic acid (GA) in triple-negative breast cancer (TNBC) therapy. GA was encapsulated into the core of the PEI-PLGA NPs while pTRAIL was adsorbed onto the positive NP surface via charge adsorption. The coating of HA on PEI-PLGA NPs functions as a targeting ligand by binding to CD44 receptor of TNBC cells and a shell to neutralize the excess positive charge of inner NPs. The resultant pTRAIL and GA co-loaded HA-coated PEI-PLGA NPs exhibited spherical shape (121.5 nm) and could promote the internalization of loaded cargoes into TNBC cells through the CD44-dependent endocytic pathway. The dual drug-loaded NPs significantly augmented apoptotic cell death in vitro and inhibited TNBC tumor growth in vivo. This multifunctional NP system efficiently co-delivered GA and pTRAIL, thus representing a promising strategy to treat TNBC and bringing forth a platform strategy for co-delivery of therapeutic DNA and chemotherapeutic agents in combinatorial TNBC therapy.
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影响因子：
4.8
作者：
Kischkel, FC;Lawrence, DA;Ashkenazi, A
通讯作者：
Ashkenazi, A
DOI：
10.1016/s1470-2045(14)70364-x
发表时间：
2014-12
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Brewster AM;Chavez-MacGregor M;Brown P
通讯作者：
Brown P
影响因子：
32.4
作者：
Wiley, SR;Schooley, K;Goodwin, RG
通讯作者：
Goodwin, RG
影响因子：
11.5
作者：
Turner, Nicholas C.;Reis-Filho, Jorge S.
通讯作者：
Reis-Filho, Jorge S.
影响因子：
82.9
作者：
Vlodavsky, I;Friedmann, Y;Pecker, I
通讯作者：
Pecker, I