Modular Synthesis of Semiconducting Graft Copolymers to Achieve "Clickable" Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

被引:12
|
作者
Creamer, Adam [1 ]
Fiego, Alessandra Lo [1 ]
Agliano, Alice [1 ]
Prados-Martin, Lino [1 ]
Hogset, Hakon [1 ]
Najer, Adrian [1 ]
Richards, Daniel. A. A. [1 ]
Wojciechowski, Jonathan. P. P. [1 ]
Foote, James E. J. [1 ]
Kim, Nayoung [1 ]
Monahan, Amy [1 ]
Tang, Jiaqing [1 ]
Shamsabadi, Andre [1 ]
Rochet, Lea N. C. [2 ]
Thanasi, Ioanna. A. A. [2 ]
de la Ballina, Laura. R. R. [3 ,4 ]
Rapley, Charlotte. L. L. [5 ]
Turnock, Stephen [6 ]
Love, Elizabeth. A. A. [7 ]
Bugeon, Laurence [8 ]
Dallman, Margaret. J. J. [8 ]
Heeney, Martin [5 ]
Kramer-Marek, Gabriela [6 ]
Chudasama, Vijay [2 ]
Fenaroli, Federico [9 ,10 ]
Stevens, Molly. M. M. [1 ]
机构
[1] Imperial Coll London, Inst Biomed Engn, Dept Mat, Dept Bioengn, London SW7 2AZ, England
[2] UCL, UCL Dept Chem, London WC1H 0AJ, England
[3] Univ Oslo, Inst Basic Med Sci, Fac Med, Dept Mol Med, N-0372 Oslo, Norway
[4] Univ Oslo, Inst Clin Med, Fac Med, Ctr Canc Cell Reprogramming, N-0450 Oslo, Norway
[5] Imperial Coll London, Dept Chem, London W12 0BZ, England
[6] Inst Canc Res, Div Radiotherapy & Imaging, Sutton SM2 5NG, Surrey, England
[7] LifeArc, Accelerator Bldg, Open Innovat Campus, Stevenage SG1 2AZ, Hertfordshire, England
[8] Imperial Coll London, Dept Life Sci, London SW7 2AZ, England
[9] Univ Stavanger, Dept Chem Biosci & Environm Engn, N-4021 Stavanger, Norway
[10] Univ Oslo, Dept Biosci, Blindernveien 31, N-0371 Oslo, Norway
基金
英国工程与自然科学研究理事会; 英国惠康基金;
关键词
fluorescent nanoparticles; graft copolymers; polymer brushes; polymer dots; semiconducting polymer nanoparticles; POLYMER NANOPARTICLES; DOTS; ANTIBODIES; MICELLES; AGENTS;
D O I
10.1002/adma.202300413
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Semiconducting polymer nanoparticles (SPNs) are explored for applications in cancer theranostics because of their high absorption coefficients, photostability, and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, a method for achieving colloidally stable and low-fouling SPNs is described by grafting poly(ethylene glycol) (PEG) onto the backbone of the fluorescent semiconducting polymer, poly(9,9 '-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole), in a simple one-step substitution reaction, postpolymerization. Further, by utilizing azide-functionalized PEG, anti-human epidermal growth factor receptor 2 (HER2) antibodies, antibody fragments, or affibodies are site-specifically "clicked" onto the SPN surface, which allows the functionalized SPNs to specifically target HER2-positive cancer cells. In vivo, the PEGylated SPNs are found to have excellent circulation efficiencies in zebrafish embryos for up to seven days postinjection. SPNs functionalized with affibodies are then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics.
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页数:14
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