Functionalization of Cellulose Nanocrystals with PEG-Metal-Chelating Block Copolymers via Controlled Conjugation in Aqueous Media.

Functionalization of Cellulose Nanocrystals with PEG-Metal-Chelating Block Copolymers via Controlled Conjugation in Aqueous Media.
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DOI:
10.1021/acsomega.6b00055
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发表时间:
2016-07-31
期刊:
影响因子:
4.1
通讯作者:
Winnik MA
Winnik MA
中科院分区:
化学3区
文献类型:
--
作者:
Guo M;Her S;Keunen R;Zhang S;Allen C;Winnik MA

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最近已经显示,在药物递送应用中,细长纳米颗粒相对于其球形对应物具有明显的优势。纤维素纳米晶体(CNCs)在自然界中具有棒状形状,并在多种哺乳动物细胞系中表现出生物相容性。在这份报告中,提出了CNCs作为生产用于癌症成像和治疗的多功能棒状纳米颗粒的模块化平台。首次公开了含有二亚乙基三胺五乙酸(DTPA)的PEG化金属螯合聚合物(即,mPEG-PGlu(DPTA)18-HyNic和PEG-PGlu(DPTA)25-HyNic)与CNC缀合以使得能够螯合放射性核素用于诊断和治疗应用。整个共轭是基于UV/可见光可定量的双芳基腙键的形成,这允许直接定量接枝到CNC上的聚合物。此外,已经表明,每个CNC接枝的聚合物的平均数量可以控制。通过将探针包埋在聚合物冠中,还用罗丹明和Alexa Fluor 488荧光标记CNC。在人卵巢癌细胞系(HEYA 8)中的初步评价表明,这些CNCs是无毒的,并且它们的渗透特性可以通过光学成像在多细胞肿瘤球体(MCTS)中容易地进行评估。这些发现为CNCs的生物医学应用提供了支持,并且进一步的体外和体内研究有必要评估其作为癌症治疗的成像和治疗剂的潜力。
Elongated nanoparticles have recently been shown to have distinct advantages over their spherical counterparts in drug delivery applications. Cellulose nanocrystals (CNCs) have rodlike shapes in nature and have demonstrated biocompatibility in a variety of mammalian cell lines. In this report, CNCs are put forward as a modular platform for the production of multifunctional rod-shaped nanoparticles for cancer imaging and therapy. For the first time, PEGylated metal-chelating polymers containing diethylenetriaminepentaacetic acid (DTPA) (i.e., mPEG-PGlu(DPTA)18-HyNic and PEG-PGlu(DPTA)25-HyNic) are conjugated to CNCs to enable the chelation of radionuclides for diagnostic and therapeutic applications. The entire conjugation is based on UV/vis-quantifiable bis-aryl hydrazone-bond formation, which allows direct quantification of the polymers grafted onto the CNCs. Moreover, it has been shown that the mean number of polymers grafted per CNC could be controlled. The CNCs are also fluorescently labeled with rhodamine and Alexa Fluor 488 by embedding the probes in the polymer corona. Preliminary evaluation in a human ovarian cancer cell line (HEYA8) demonstrated that these CNCs are nontoxic and their penetration properties can be readily assessed in multicellular tumor spheroids (MCTSs) by optical imaging. These findings provide support for biomedical applications of CNCs, and further in vitro and in vivo studies are warranted to evaluate their potential as imaging and therapeutic agents for cancer treatment.
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