Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy.
Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy.
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DOI：
10.2147/ijn.s32804
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发表时间：
2012
影响因子：
8
通讯作者：
Fang Y
中科院分区：
文献类型：
--
作者：
Gao X;Luo Y;Wang Y;Pang J;Liao C;Lu H;Fang Y
我们设计了用于体内应用的双功能纳米颗粒，使用改进的静电和共价逐层组装策略来应对激素难治性前列腺癌的评估和治疗的挑战。将聚(D，L-乳酸-羟基乙酸)、多西紫杉醇和疏水性超顺磁性氧化铁纳米晶(SPION)组成的核，由聚烯丙胺盐酸盐和两个不同大小的聚乙二醇分子形成的多层壳，以及连接到纳米粒表面的单链前列腺干细胞抗体靶向传递，形成了核壳纳米粒。药物释放曲线表明，双功能纳米粒具有764小时的缓释模式，SPIOns可促进药物的体外控释。通过将多西紫杉醇和SPION靶向输送到PC3M细胞，该纳米粒显示出更高的抗肿瘤效率和增强了体外磁共振成像。此外，在携带PC3M异种移植瘤的裸鼠身上，纳米颗粒在76天的研究期间提供了MRI负对比增强，以及阻止甚至逆转肿瘤生长，并且没有明显的全身毒性。使用这些靶向双功能纳米颗粒治疗的小鼠的寿命显著延长(卡方=22.514，P<；0.0001)。这种双功能纳米医学平台在肿瘤成像和体内靶向给药方面可能是一个很有前途的候选者。
We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer. Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid), docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs), a multilayer shell formed by poly(allylamine hydrochloride) and two different sized poly(ethylene glycol) molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery. Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001). This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo.