HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells

被引:21
作者
Yamaguchi, Haruka [1 ,2 ]
Hayama, Kazuhide [2 ]
Sasagawa, Ichiro [3 ]
Okada, Yasuo [4 ]
Kawase, Tomoyuki [5 ]
Tsubokawa, Norio [6 ]
Tsuchimochi, Makoto [7 ]
机构
[1] Nippon Dent Univ, Dept Life Sci Dent, Chuo Ku, 1-8 Hamauracho, Niigata 9518580, Japan
[2] Nippon Dent Univ, Sch Life Dent Niigata, Dept Oral & Maxillofacial Radiol, Niigata 9518580, Japan
[3] Nippon Dent Univ, Sch Life Dent Niigata, Adv Res Ctr, Niigata 9518580, Japan
[4] Nippon Dent Univ, Sch Life Dent Niigata, Dept Pathol, Niigata 9518580, Japan
[5] Niigata Univ, Grad Sch Med & Dent Sci, Dept Tissue Regenerat & Reconstitut, Div Oral Bioengn, Niigata 9518541, Japan
[6] Niigata Univ, Fac Engn, Niigata 9502181, Japan
[7] Nippon Dent Univ Tokyo, Tokyo 1028159, Japan
基金
日本学术振兴会;
关键词
silica nanoparticle; HER2; radiosensitizer; SK-BR3; SIZE-DEPENDENT CYTOTOXICITY; IN-VITRO; ENDOTHELIAL-CELLS; TARGETED PROBES; APOPTOSIS; DEATH; INTERNALIZATION; RADIOTHERAPY; LYSOSOMES; PARTICLES;
D O I
10.3390/ijms19030908
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells.
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页数:13
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共 40 条
  • [1] The lysosome: from waste bag to potential therapeutic target
    Appelqvist, Hanna
    Waster, Petra
    Kagedal, Katarina
    Ollinger, Karin
    [J]. JOURNAL OF MOLECULAR CELL BIOLOGY, 2013, 5 (04) : 214 - 226
  • [2] Interaction of Spherical Silica Nanoparticles with Neuronal Cells: Size-Dependent Toxicity and Perturbation of Calcium Homeostasis
    Ariano, Paolo
    Zamburlin, Pollyanna
    Gilardino, Alessandra
    Mortera, Renato
    Onida, Barbara
    Tomatis, Maura
    Ghiazza, Mara
    Fubini, Bice
    Lovisolo, Davide
    [J]. SMALL, 2011, 7 (06) : 766 - 774
  • [3] Belz J, 2017, METHODS MOL BIOL, V1530, P403, DOI 10.1007/978-1-4939-6646-2_26
  • [4] Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma
    Benezra, Miriam
    Penate-Medina, Oula
    Zanzonico, Pat B.
    Schaer, David
    Ow, Hooisweng
    Burns, Andrew
    DeStanchina, Elisa
    Longo, Valerie
    Herz, Erik
    Iyer, Srikant
    Wolchok, Jedd
    Larson, Steven M.
    Wiesner, Ulrich
    Bradbury, Michelle S.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (07) : 2768 - 2780
  • [5] Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions
    Bradbury, Michelle S.
    Phillips, Evan
    Montero, Pablo H.
    Cheal, Sarah M.
    Stambuk, Hilda
    Durack, Jeremy C.
    Sofocleous, Constantinos T.
    Meester, Richard J. C.
    Wiesner, Ulrich
    Patel, Snehal
    [J]. INTEGRATIVE BIOLOGY, 2013, 5 (01) : 74 - 86
  • [6] Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines
    Breznan, Dalibor
    Das, Dharani D.
    O'Brien, Julie S.
    MacKinnon-Roy, Christine
    Nimesh, Surendra
    Vuong, Ngoc Q.
    Bernatchez, Stephane
    DeSilva, Nimal
    Hill, Myriam
    Kumarathasan, Prem
    Vincent, Renaud
    [J]. NANOTOXICOLOGY, 2017, 11 (02) : 223 - 235
  • [7] In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line
    Chang, Jenq-Sheng
    Chang, Ke Liang B.
    Hwang, Deng-Fwu
    Kong, Zwe-Ling
    [J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY, 2007, 41 (06) : 2064 - 2068
  • [8] Molecular Elucidation of Biological Response to Mesoporous Silica Nanoparticles in Vitro and in Vivo
    Chou, Cheng-Chung
    Chen, Wei
    Hung, Yann
    Mou, Chung-Yuan
    [J]. ACS APPLIED MATERIALS & INTERFACES, 2017, 9 (27) : 22235 - 22251
  • [9] Evidence-based Estimates of the Demand for Radiotherapy
    Delaney, G. P.
    Barton, M. B.
    [J]. CLINICAL ONCOLOGY, 2015, 27 (02) : 70 - 76
  • [10] Cardiovascular toxicity evaluation of silica nanoparticles in endothelial cells and zebrafish model
    Duan, Junchao
    Yu, Yongbo
    Li, Yang
    Yu, Yang
    Sun, Zhiwei
    [J]. BIOMATERIALS, 2013, 34 (23) : 5853 - 5862