文献：Self-assembly of paramagnetic amphiphiliccopolymers for synergistic therapy

文献链接：https://pubs.rsc.org/en/content/articlelanding/2020/tb/d0tb00405g

作者：Zhiliang Gao,Weiwei Mu, Yuan Tian,Yimao Su,Huanli Sun,Gaorui Zhang, Anning Li,DexinYu,Na Zhang,Jingcheng Hao, Yongjun Liu and Jiwei Cui

相关产品：PCL44-b-PEG113

原文摘要：Engineering nanoparticles (NPs) with multifunctionality has become a promising strategy for cancer theranostics. Herein, theranostic polymer NPs are fabricated via the assembly of amphiphilic paramagnetic block copolymers (PCL-b-PIEtMn), in which IR-780 and doxorubicin (DOX) were co-encapsulated, for magnetic resonance (MR) and near infrared fluorescence (NIRF) imaging as well as for photo thermal therapy (PTT)-enhanced chemotherapy. The synthesized amphiphilic paramagnetic block copolymers demonstrated high relaxivity (r1 = 7.05 mM 1 s  1 ). The encapsulated DOX could be released with the trigger of near infrared (NIR) light. In vivo imaging confirmed that the paramagnetic NPs could be accumulated effectively at the tumor sites. Upon the NIR laser irradiation, tumor growth was inhibited by PTT-enhanced chemotherapy. The advantages of the reported system lie in the one-step convergence of multiple functions (i.e., imaging and therapy agents) into a one delivery vehicle and the dual mode imaging-guided synergistic PTT and chemotherapy. This study represents a new drug delivery vehicle of

paramagnetic NPs for visualized theranostics.

PCL-b-PEG是一种嵌段共聚物，由聚己内酯（PCL）和聚乙二醇（PEG）组成。PCL是一种具有良好生物降解性和机械性能的聚合物，而PEG则具有良好的水溶性和生物相容性。两者结合形成的PCL-b-PEG嵌段共聚物兼具了这两种特性。其可以自组装形成纳米粒子，将药物包裹在内部，通过调节PCL和PEG的比例，可以控制药物的释放速率，实现长效的药物释放。同时，由于PEG的存在，纳米粒子可以避免被免疫系统识别和清除，提高药物的生物利用度。多功能工程纳米颗粒（NPs）已成为一种很有前途的cancer应用策略。基于此通过组装两亲性顺磁嵌段共聚物（PCL-b-PIEtMn）来制造Treatment 聚合物NPs，其中IR-780和阿霉素（DOX）共封装，用于磁共振（MR）和近红外荧光（NIRF）成像以及（PTT）增强效果。

图：顺磁性NPs的制备

制备顺磁性聚合物NPs

采用共溶剂法制备了顺磁性聚合物NPs。将PCL-b-PIEtMn共聚物和PCL-bPEG溶解在DMF中，用注射泵剧烈搅拌滴加入水。用水透析，去除DMF，用超滤浓缩。将DOX与三乙胺在DMF中混合，去除DOX上的盐酸。将处理后的DOX溶液在DMF、IR-780、PCL-b-PIEtMn共聚物和PCL-b-PEG中溶解在DMF中，然后滴加入水。

图：MCF-7细胞在游离DOX或DOX&IR-780@NPs孵育4小时后的CLSM图像用Hoechst（蓝色）和小麦胚芽凝集素Alexa Fluor 488偶联物（绿色）分别对细胞核和细胞膜进行染色。

结论：PCL44-b-PEG113参与合成的两亲性顺磁嵌段共聚物具有较高的弛豫率（r1 = 7.05 mM 1 s 1）。封装的DOX可以通过近红外（NIR）光的触发器来释放。体内成像证实，顺磁性NPs可以在tumor部位有效积累。在NIR激光照射下，ptt增强Chemotherapy 可抑制tumor生长。其优点在于可以将多种功能（即成像和应用药物）一步融合到一个给药载体，以及双模式成像引导的协同PTT。