MOE Key Laboratory for Analytical Science of Food Safety and Biology, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou 350116, People's Republic of China.
College of Biological Science and Engineering, Fuzhou University , Fuzhou 350116, People's Republic of China.
ACS Appl Mater Interfaces. 2017 Sep 13;9(36):30502-30509. doi: 10.1021/acsami.7b10086. Epub 2017 Aug 30.
The mononuclear phagocyte system (MPS) with key roles in recognition and clearance of foreign particles, is a major constraint to nanoparticle-based delivery systems. The desire to improve the delivery efficiency has prompted the search for stealthy long-circulating nanoplatforms. Herein, we design an antiphagocytic delivery system with "active" stealth behavior for cancer theranostics combining efficient MRI and enhanced drug delivery. We modify self-peptide, a synthetic peptide for active immunomodulation, to biodegradable poly(lactide-glycolide)-poly(ethylene glycol) (PLGA-PEG), then utilize the self-assembly properties of PLGA-PEG to form nanomicelles that encapsulating iron oxide (IO) nanoparticles and anticancer drug paclitaxel (PTX). Through the interaction of self-peptide with the receptor SIRPα, which is expressed on phagocytes, the as-prepared nanomicelles can disguise as "self" to avoid being recognized as foreign particles by MPS, leading to improved blood circulation time and delivery efficiency. Compared to the "passive" stealth effect generating by PEG or zwitterionic polymers that only passively delay the physisorption of serum proteins to nanocarriers, the "active self" nanomicelles can more efficiently inhibit the MPS-mediated immune clearance and reduce "accelerated blood clearance" phenomenon. Furthermore, this one-step clustering of IO nanoparticles and loading of PTX endow the resulted magneto-nanomicelles with enhanced T MRI contrast performance and antitumor effect. We believe that this study provides a novel approach in designing of efficient stealth antiphagocytic delivery systems that resisting the MPS-mediated clearance for cancer theranostics.
单核吞噬细胞系统（MPS）在识别和清除外来颗粒方面起着关键作用，是纳米颗粒给药系统的主要限制因素。提高递送效率的愿望促使人们寻求具有隐身性和长循环的纳米平台。在此，我们设计了一种具有“主动”隐身行为的抗吞噬递药系统，用于癌症治疗学，结合高效 MRI 和增强药物递送。我们将用于主动免疫调节的合成肽自肽修饰为可生物降解的聚（乳酸-羟基乙酸）-聚乙二醇（PLGA-PEG），然后利用 PLGA-PEG 的自组装特性形成纳米胶束，包封氧化铁（IO）纳米颗粒和抗癌药物紫杉醇（PTX）。通过自肽与表达在吞噬细胞上的受体 SIRPα 的相互作用，所制备的纳米胶束可以伪装成“自身”，以避免被 MPS 识别为外来颗粒，从而延长血液循环时间并提高递送效率。与通过被动延迟血清蛋白与纳米载体的物理吸附而仅产生“被动”隐身效果的 PEG 或两性聚合物相比，“主动自我”纳米胶束可以更有效地抑制 MPS 介导的免疫清除，并减少“加速血液清除”现象。此外，IO 纳米颗粒的一步聚集和 PTX 的加载赋予所得磁纳米胶束增强的 T1 MRI 对比性能和抗肿瘤作用。我们相信，这项研究为设计用于癌症治疗学的高效隐身抗吞噬递药系统提供了一种新方法，该系统可抵抗 MPS 介导的清除。
