Specific Drug Delivery to Cancer Cells with Double-Imprinted Nanoparticles against Epidermal Growth Factor Receptor

被引:125
作者
Canfarotta, Francesco [1 ]
Lezina, Larissa [2 ]
Guerreiro, Antonio [1 ]
Czulak, Joanna [1 ]
Petukhov, Alexey [4 ,5 ]
Daks, Alexandra [4 ]
Smolinska-Kempisty, Katarzyna [3 ]
Poma, Alessandro [6 ]
Piletsky, Sergey
Barlev, Nickolai A. [4 ,7 ]
机构
[1] MIP Diagnost Ltd, Fielding Johnson Bldg, Leicester LE1 7RH, Leics, England
[2] Univ Leicester, Dept Canc Studies, Leicester LE1 7RH, Leics, England
[3] Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England
[4] Inst Cytol, Lab Gene Express & Regulat, St Petersburg 194064, Russia
[5] Almazov Natl Med Res Ctr, Inst Hematol, St Petersburg 197341, Russia
[6] UCL, Chem Dept, London WC1H 0AJ, England
[7] Moscow Inst Phys & Technol, Dolgoprudnyi 141700, Moscow Oblast, Russia
基金
英国国家替代、减少和改良动物研究中心; 俄罗斯科学基金会;
关键词
Molecular imprinting; nanoparticles; molecular recognition; membrane receptors; cancer; drug delivery; SOLID-PHASE SYNTHESIS; POLYMER NANOPARTICLES; PLASTIC ANTIBODY; PROTEINS; EGFR; 4-ETHYLPHENOL; RECOGNITION; FLUORESCENT; MIMICS; ASSAY;
D O I
10.1021/acs.nanolett.7b03206
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is over-expressed in many tumors, including almost half of triple-negative breast cancers. The latter belong to a very-aggressive and drug-resistant form of malignancy. Although humanized anti-EGFR antibodies can work efficiently against these cancers both as monotherapy and in combination with genotoxic drugs, instability and high production costs are some of their known drawbacks in clinical use. In addition, the development of antibodies to target membrane proteins is a very challenging task. Accordingly, the main focus of the present work is the design of supramolecular agents for the targeting of membrane proteins in cancer cells and, hence, more-specific drag delivery. These were produced using a novel double-imprinting approach based on the solid-phase method for preparation of molecularly imprinted polymer nanoparticles (nanoMIPs), which were loaded with doxorubicin and targeted toward a linear epitope of EGFR. Additionally, upon binding, doxorubicin-loaded anti-EGFR nanoMIPs elicited cytotoxicity and apoptosis only in those cells that over-expressed EGFR. Thus, this approach can provide a plausible alternative to conventional antibodies and sets up a new paradigm for the therapeutic application of this class of materials against clinically relevant targets. Furthermore, nanoMIPs can promote the development of cell imaging tools against difficult targets such as membrane proteins.
引用
收藏
页码:4641 / 4646
页数:6
相关论文
共 29 条
  • [1] Solid-phase synthesis of molecularly imprinted nanoparticles for protein recognition
    Ambrosini, Serena
    Beyazit, Selim
    Haupt, Karsten
    Bui, Bernadette Tse Sum
    [J]. CHEMICAL COMMUNICATIONS, 2013, 49 (60) : 6746 - 6748
  • [2] Direct potentiometric quantification of histamine using solid-phase imprinted nanoparticles as recognition elements
    Basozabal, Itsaso
    Guerreiro, Antonio
    Gomez-Caballero, Alberto
    Aranzazu Goicolea, M.
    Barrio, Ramon J.
    [J]. BIOSENSORS & BIOELECTRONICS, 2014, 58 : 138 - 144
  • [3] Modulation of protein-protein interactions with small organic molecules
    Berg, T
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (22) : 2462 - 2481
  • [4] Does size matter? Study of performance of pseudo-ELISAs based on molecularly imprinted polymer nanoparticles prepared for analytes of different sizes
    Caceres, C.
    Canfarotta, F.
    Chianella, I.
    Pereira, E.
    Moczko, E.
    Esen, C.
    Guerreiro, A.
    Piletska, E.
    Whitcombe, M. J.
    Piletsky, S. A.
    [J]. ANALYST, 2016, 141 (04) : 1405 - 1412
  • [5] Biocompatibility and internalization of molecularly imprinted nanoparticles
    Canfarotta, Francesco
    Waters, Alicia
    Sadler, Robyn
    McGill, Paul
    Guerreiro, Antonio
    Papkovsky, Dmitri
    Haupt, Karsten
    Piletsky, Sergey
    [J]. NANO RESEARCH, 2016, 9 (11) : 3463 - 3477
  • [6] Solid-phase synthesis of molecularly imprinted nanoparticles
    Canfarotta, Francesco
    Poma, Alessandro
    Guerreiro, Antonio
    Piletsky, Sergey
    [J]. NATURE PROTOCOLS, 2016, 11 (03) : 443 - 455
  • [7] Direct Replacement of Antibodies with Molecularly Imprinted Polymer Nanoparticles in ELISA-Development of a Novel Assay for Vancomycin
    Chianella, Iva
    Guerreiro, Antonio
    Moczko, Ewa
    Caygill, J. Sarah
    Piletska, Elena V.
    Sansalvador, Isabel M. Perez De Vargas
    Whitcombe, Michael J.
    Piletsky, Sergey A.
    [J]. ANALYTICAL CHEMISTRY, 2013, 85 (17) : 8462 - 8468
  • [8] Fluorescent, Superparamagnetic Nanospheres for Drug Storage, Targeting, and Imaging: A Multifunctional Nanocarrier System for Cancer Diagnosis and Treatment
    Cho, Hoon-Sung
    Dong, Zhongyun
    Pauletti, Giovanni M.
    Zhang, Jiaming
    Xu, Hong
    Gu, Hongchen
    Wang, Lumin
    Ewing, Rodney C.
    Huth, Christopher
    Wang, Feng
    Shi, Donglu
    [J]. ACS NANO, 2010, 4 (09) : 5398 - 5404
  • [9] Protein-protein interfaces: mimics and inhibitors
    Cochran, AG
    [J]. CURRENT OPINION IN CHEMICAL BIOLOGY, 2001, 5 (06) : 654 - 659
  • [10] Doranz B. J., 2015, GENET ENG BIOTECHNOL, V35, P20