Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

被引:123
作者
Colombo, Miriam [1 ]
Fiandra, Luisa [2 ]
Alessio, Giulia [1 ,3 ]
Mazzucchelli, Serena [2 ,3 ]
Nebuloni, Manuela [2 ,3 ]
De Palma, Clara [2 ]
Kantner, Karsten [4 ]
Pelaz, Beatriz [4 ]
Rotem, Rany [1 ]
Corsi, Fabio [3 ,5 ]
Parak, Wolfgang J. [4 ,6 ]
Prosperi, Davide [1 ]
机构
[1] Univ Milano Bicocca, Dipartimento Biotechnol & Biosci, Piazza Sci 2, I-20126 Milan, Italy
[2] Osped L Sacco, Via G B Grassi 74, I-20157 Milan, Italy
[3] Univ Milan, Dipartimento Sci Biomed & Clin Luigi Sacco, Via G B Grassi 74, I-20157 Milan, Italy
[4] Philipps Univ Marburg, Fachbereich Phys, Renthof 7, D-35037 Marburg, Germany
[5] ICS Maugeri SpA SB, Dept Surg, Breast Unit, Via S Maugeri 10, I-27100 Pavia, Italy
[6] CIC Biomagune, Miramon Pasealekua 182, San Sebastian 20009, Spain
基金
欧盟地平线“2020”;
关键词
GOLD NANOPARTICLES; MULTIFUNCTIONAL NANOPARTICLES; INORGANIC NANOPARTICLES; AMPHIPHILIC POLYMER; QUANTUM DOTS; SIZE; TRASTUZUMAB; CONJUGATION;
D O I
10.1038/ncomms13818
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect.
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页数:14
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