Facile Synthesis of Gadolinium Chelate-Conjugated Polymer Nanoparticles for Fluorescence/Magnetic Resonance Dual-Modal Imaging

被引:26
作者
Pan, Yi [1 ]
Chen, Wandi [1 ]
Yang, Jun [2 ]
Zheng, Junhui [2 ]
Yang, Mengsu [3 ]
Yi, Changqing [1 ]
机构
[1] Sun Yat Sen Univ, Sch Engn, Key Lab Sensing Technol & Biomed Instruments Guan, Guangzhou, Guangdong, Peoples R China
[2] Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China
[3] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Hong Kong, Peoples R China
关键词
CARBON QUANTUM DOTS; ONE-POT SYNTHESIS; MAGNETIC-RESONANCE; DRUG-DELIVERY; IN-VIVO; GENE DELIVERY; CONTRAST AGENTS; NANOCOMPOSITES; NANOPROBE; THERAPY;
D O I
10.1021/acs.analchem.7b04078
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Fluorescence (FL)/magnetic resonance (MR) dual-modal imaging nanoprobes are significant not only for cutting edge research in molecular imaging, but also for clinical diagnosis with high precision and accuracy. However, synthesis of FL/MR dual-modal imaging nanoprobes that simultaneously exhibit strong fluorescent brightness and high MR response, long-term colloidal stability with uniform sizes, good biocompatibility and a versatile surface functionality has proven challenging. In this study, the well-defined core-shell structured Gd3+ chelate-conjugated fluorescent polymer nano particles (Gd-FPNPs) that consist of rhodamine B (RB)encapsulated poly(methyl methacrylate) (PMMA) cores and Gd3+ chelate-conjugated branched polyethylenimine (PEI) shells, are facilely synthesized via a one-step graft copolymerization of RB-encapsulated MMA from PEI-DTPA-Gd induced by tert-butyl hydroperoxide (TBHP) at 80 degrees C for 2 h. The mild synthesis route not only preserves the chemical environment for Gd3+ coordination, but also improves optical properties and chemo-/photostability of RB. A high local concentration of outer surface-chelated Gd3+ dand their direct interactions with hydrogen protons endow Gd-FPNPs high longitudinal relaxivity (26.86 mM(-1) s(-1)). The uniform spherical structure of Gd-FPNPs facilitates their biotransfer, and their surface carboxyl and amine groups afford them both long-term colloidal stability and cell-membrane permeability. The excellent biocompatibility and FL/MR dual modal imaging capability of Gd-FPNPs are demonstrated using HeLa cells and mice as models. All the results confirm that Gd-FPNPs fulfill the design criteria for a high-performance imaging nanoprobe. In addition, this study enables such probes to be prepared also by those not skilled in nanomaterial synthesis, and thus promoting the development of novel functional imaging nanoprobes.
引用
收藏
页码:1992 / 2000
页数:9
相关论文
共 52 条
[1]   Biodistribution of Gadolinium-Based Contrast Agents, Including Gadolinium Deposition [J].
Aime, Silvio ;
Caravan, Peter .
JOURNAL OF MAGNETIC RESONANCE IMAGING, 2009, 30 (06) :1259-1267
[2]   How to determine free Gd and free ligand in solution of Gd chelates. A technical note [J].
Barge, Alessandro ;
Cravotto, Giancarlo ;
Gianolio, Eliana ;
Fedeli, Franco .
CONTRAST MEDIA & MOLECULAR IMAGING, 2006, 1 (05) :184-188
[3]   First soluble M@C60 derivatives provide enhanced access to metallofullerenes and permit in vivo evaluation of Gd@C60[C(COOH)2]10 as a MRI contrast agent [J].
Bolskar, RD ;
Benedetto, AF ;
Husebo, LO ;
Price, RE ;
Jackson, EF ;
Wallace, S ;
Wilson, LJ ;
Alford, JM .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (18) :5471-5478
[4]   A VERSATILE VECTOR FOR GENE AND OLIGONUCLEOTIDE TRANSFER INTO CELLS IN CULTURE AND IN-VIVO - POLYETHYLENIMINE [J].
BOUSSIF, O ;
LEZOUALCH, F ;
ZANTA, MA ;
MERGNY, MD ;
SCHERMAN, D ;
DEMENEIX, B ;
BEHR, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (16) :7297-7301
[5]   Fluorescent imaging of cancerous tissues for targeted surgery [J].
Bu, Lihong ;
Shen, Baozhong ;
Cheng, Zhen .
ADVANCED DRUG DELIVERY REVIEWS, 2014, 76 :21-38
[6]   Facile Hydrothermal Synthesis and Surface Functionalization of Polyethyleneimine-Coated Iron Oxide Nanoparticles for Biomedical Applications [J].
Cai, Hongdong ;
An, Xiao ;
Cui, Jun ;
Li, Jingchao ;
Wen, Shihui ;
Li, Kangan ;
Shen, Mingwu ;
Zheng, Linfeng ;
Zhang, Guixiang ;
Shi, Xiangyang .
ACS APPLIED MATERIALS & INTERFACES, 2013, 5 (05) :1722-1731
[7]   Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics, and applications [J].
Caravan, P ;
Ellison, JJ ;
McMurry, TJ ;
Lauffer, RB .
CHEMICAL REVIEWS, 1999, 99 (09) :2293-2352
[8]   Gd3+-Ion-Doped Upconversion Nanoprobes: Relaxivity Mechanism Probing and Sensitivity Optimization [J].
Chen, Feng ;
Bu, Wenbo ;
Zhang, Shengjian ;
Liu, Jianan ;
Fan, Wenpei ;
Zhou, Liangping ;
Peng, Weijun ;
Shi, Jianlin .
ADVANCED FUNCTIONAL MATERIALS, 2013, 23 (03) :298-307
[9]   Gd-Encapsulated Carbonaceous Dots with Efficient Renal Clearance for Magnetic Resonance Imaging [J].
Chen, Hongmin ;
Wang, Geoffrey D. ;
Tang, Wei ;
Todd, Trever ;
Zhen, Zipeng ;
Tsang, Chu ;
Hekmatyar, Khan ;
Cowger, Taku ;
Hubbard, Richard B. ;
Zhang, Weizhong ;
Stickney, John ;
Shen, Baozhong ;
Xie, Jin .
ADVANCED MATERIALS, 2014, 26 (39) :6761-6766
[10]   Magneto-fluorescent core-shell supernanoparticles [J].
Chen, Ou ;
Riedemann, Lars ;
Etoc, Fred ;
Herrmann, Hendrik ;
Coppey, Mathieu ;
Barch, Mariya ;
Farrar, Christian T. ;
Zhao, Jing ;
Bruns, Oliver T. ;
Wei, He ;
Guo, Peng ;
Cui, Jian ;
Jensen, Russ ;
Chen, Yue ;
Harris, Daniel K. ;
Cordero, Jose M. ;
Wang, Zhongwu ;
Jasanoff, Alan ;
Fukumura, Dai ;
Reimer, Rudolph ;
Dahan, Maxime ;
Jain, Rakesh K. ;
Bawendi, Moungi G. .
NATURE COMMUNICATIONS, 2014, 5