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从一到多:用于肿瘤靶向成像和程序光活性治疗的自组装治疗性纳米粒子。

From one to all: self-assembled theranostic nanoparticles for tumor-targeted imaging and programmed photoactive therapy.

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, No. 11 First North Road, Zhongguancun, Beijing, 100190, China.

University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.

出版信息

J Nanobiotechnology. 2019 Feb 2;17(1):23. doi: 10.1186/s12951-019-0450-x.

Abstract

BACKGROUND

In recent years, multifunctional theranostic nanoparticles have been fabricated by integrating imaging and therapeutic moieties into one single nano-formulations. However, Complexity of production and safety issues limits their further application.

RESULTS

Herein, we demonstrated self-assembled nanoparticles with single structure as a "from one to all" theranostic platform for tumor-targeted dual-modal imaging and programmed photoactive therapy (PPAT). The nanoparticles were successfully developed through self-assembling of hyaluronic acid (HA)-cystamine-cholesterol (HSC) conjugate, in which IR780 was simultaneously incorporated (HSCI NPs). Due to the proper hydrodynamic size and intrinsic targeting ability of HA, the HSCI NPs could accumulate at the tumor site effectively after systemic administration. In the presence of incorporated IR780, in vivo biodistribution and accumulation behaviors of HSCI NPs could be monitored by photoacoustic imaging. After cellular uptake, the HSCI NPs would disintegrate resulting from cystamine reacting with over-expressed GSH. The released IR780 would induce fluorescence "turn-on" conversion, which could be used to image tumor sites effectively. Upon treatment with 808 nm laser irradiation, PPAT could be achieved in which generated reactive oxygen species (ROS) would produce photodynamic therapy (PDT), and subsequently the raised temperature would be beneficial to tumor photothermal therapy (PTT).

CONCLUSION

The self-assembled HSCI NPs could act as "from one to all" theranostic platform for high treatment efficiency via PPAT pattern, which could also real-time monitor NPs accumulation by targeted and dual-modal imaging in a non-invasive way.

摘要

背景

近年来,多功能治疗性纳米粒子已通过将成像和治疗部分整合到单个纳米制剂中而被制备出来。然而,生产的复杂性和安全问题限制了它们的进一步应用。

结果

本文中,我们展示了具有单一结构的自组装纳米粒子作为一种用于肿瘤靶向双模式成像和程序性光活性治疗(PPAT)的“从一到全”治疗平台。该纳米粒子是通过透明质酸(HA)-半胱胺-胆固醇(HSC)缀合物的自组装成功开发的,其中同时掺入了 IR780(HSCI NPs)。由于 HA 的适当流体力学尺寸和固有靶向能力,HSCI NPs 在全身给药后可以有效地在肿瘤部位积聚。在掺入的 IR780 的存在下,可以通过光声成像监测 HSCI NPs 的体内分布和积累行为。细胞摄取后,由于半胱胺与过表达的 GSH 反应,HSCI NPs 会分解。释放的 IR780 将诱导荧光“开启”转换,可有效用于成像肿瘤部位。在用 808nm 激光照射治疗时,可以实现 PPAT,其中产生的活性氧(ROS)将产生光动力疗法(PDT),随后升高的温度将有利于肿瘤光热疗法(PTT)。

结论

自组装的 HSCI NPs 可以作为通过 PPAT 模式实现高效治疗的“从一到全”治疗平台,还可以通过靶向和双模式成像以非侵入性方式实时监测 NPs 的积累。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f42/6359812/1f8d055cb2a1/12951_2019_450_Sch1_HTML.jpg

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