Specific targeting and noninvasive imaging of breast cancer stem cells using single-walled carbon nanotubes as novel multimodality nanoprobes.

BACKGROUND The limitation of current breast cancer treatments was elucidated by the presence of cancer stem cells (CSCs) that play essential role in cancer initiation, progression, resistance, recurrence and metastasis. Materials & methods: Biocompatible multimodality single-walled carbon nanotube (SWCNT) nanoprobes were developed. The biodistribution and preferential homing of CD44 antibody-conjugated SWCNTs toward the tumor site were monitored using MRI, single-photon emission computed tomography and near-infrared fluorescence imaging noninvasive imaging modalities. RESULTS Quantification of SWCNTs by sensitively measuring iron content in sorted CSC populations using inductively coupled plasma-mass spectrometry confirmed the enhanced selective targeting of anti-CD44 SWCNT and immunohistochemistry analyses revealed enhanced colocalization with areas rich in CD44 receptors. DISCUSSION & CONCLUSION This preclinical study provided encouraging results for efficient targeting of breast CSCs and perspectives for further clinical studies to confirm the efficacy and safety of the designed nanocarriers.

[1]  F. Mannello Understanding breast cancer stem cell heterogeneity: time to move on to a new research paradigm , 2013, BMC Medicine.

[2]  R. Weissleder,et al.  Fluorescence molecular imaging of small animal tumor models. , 2004, Current molecular medicine.

[3]  Harikrishna Nakshatri,et al.  CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis , 2006, Breast Cancer Research.

[4]  Michael E Phelps,et al.  Positron emission tomography scanning: current and future applications. , 2002, Annual review of medicine.

[5]  M. Adeli,et al.  Carbon nanotubes in cancer therapy: a more precise look at the role of carbon nanotube-polymer interactions. , 2013, Chemical Society reviews.

[6]  Arun Sharma,et al.  Nanocarriers for Diagnosis and Targeting of Breast Cancer , 2013, BioMed research international.

[7]  R. Halwani,et al.  Preferential Macrophage Recruitment and Polarization in LPS-Induced Animal Model for COPD: Noninvasive Tracking Using MRI , 2014, PloS one.

[8]  K. Siziopikou,et al.  The role of cancer stem cells in breast cancer initiation and progression: potential cancer stem cell-directed therapies. , 2012, The oncologist.

[9]  A. Al Faraj,et al.  Magnetic single-walled carbon nanotubes as efficient drug delivery nanocarriers in breast cancer murine model: noninvasive monitoring using diffusion-weighted magnetic resonance imaging as sensitive imaging biomarker , 2014, International journal of nanomedicine.

[10]  Ke Chen,et al.  Understanding and targeting cancer stem cells: therapeutic implications and challenges , 2013, Acta Pharmacologica Sinica.

[11]  A. Mukhopadhyay,et al.  Breast cancer stem cells: a novel therapeutic target. , 2013, Clinical breast cancer.

[12]  A. Al Faraj,et al.  Preferential magnetic targeting of carbon nanotubes to cancer sites: noninvasive tracking using MRI in a murine breast cancer model. , 2015, Nanomedicine.

[13]  H. Ali-Boucetta,et al.  Pharmacology of carbon nanotubes: toxicokinetics, excretion and tissue accumulation. , 2013, Advanced drug delivery reviews.

[14]  A. Jemal,et al.  Cancer statistics, 2013 , 2013, CA: a cancer journal for clinicians.

[15]  Michael Dean,et al.  Tumour stem cells and drug resistance , 2005, Nature Reviews Cancer.

[16]  J. Peterse,et al.  Breast cancer metastasis: markers and models , 2005, Nature Reviews Cancer.

[17]  Bo Zhang,et al.  Carbon nanotubes in cancer diagnosis and therapy. , 2010, Biochimica et biophysica acta.

[18]  David A. Benaron,et al.  The Future of Cancer Imaging , 2004, Cancer and Metastasis Reviews.

[19]  F. Bertucci,et al.  Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. , 2009, Cancer research.

[20]  M. Diehn,et al.  Cancer stem cells and radiotherapy: new insights into tumor radioresistance. , 2006, Journal of the National Cancer Institute.

[21]  Jaime Conceição,et al.  Nanotechnological carriers for cancer chemotherapy: the state of the art. , 2015, Colloids and surfaces. B, Biointerfaces.

[22]  Chao Li,et al.  CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells , 2015, Theranostics.

[23]  Zhuang Liu,et al.  Carbon nanotubes for biomedical imaging: the recent advances. , 2013, Advanced drug delivery reviews.

[24]  S. Okarvi,et al.  Preparation and in vitro and in vivo evaluation of technetium-99m-labeled folate and methotrexate conjugates as tumor imaging agents. , 2006, Cancer biotherapy & radiopharmaceuticals.

[25]  J. Schroeder,et al.  Understanding the Dual Nature of CD44 in Breast Cancer Progression , 2011, Molecular Cancer Research.

[26]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  A. Jemal,et al.  Breast cancer statistics, 2013 , 2014, CA: a cancer journal for clinicians.

[28]  S. Badve,et al.  Biomarkers for breast cancer stem cells: the challenges ahead. , 2011, Biomarkers in medicine.

[29]  S. Okarvi,et al.  Design, synthesis, radiolabeling and in vitro and in vivo characterization of tumor-antigen- and antibody-derived peptides for the detection of breast cancer. , 2009, Anticancer research.

[30]  Xiaoyang Xu,et al.  Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. , 2014, Advanced drug delivery reviews.

[31]  Alexander V Kabanov,et al.  Can nanomedicines kill cancer stem cells? , 2013, Advanced drug delivery reviews.

[32]  Feng Liang,et al.  A review on biomedical applications of single-walled carbon nanotubes. , 2010, Current medicinal chemistry.

[33]  Jinwoo Cheon,et al.  Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging , 2007, Nature Medicine.

[34]  Maurizio Prato,et al.  Endowing carbon nanotubes with biological and biomedical properties by chemical modifications. , 2013, Advanced drug delivery reviews.

[35]  K Kostarelos,et al.  Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. , 2009, Nature nanotechnology.

[36]  Shuk Han Cheng,et al.  Nanotherapeutics in angiogenesis: synthesis and in vivo assessment of drug efficacy and biocompatibility in zebrafish embryos , 2011, International journal of nanomedicine.

[37]  David A Scheinberg,et al.  Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes , 2010, International journal of nanomedicine.

[38]  Jia-You Fang,et al.  Nanoparticles as delivery carriers for anticancer prodrugs , 2012, Expert opinion on drug delivery.

[39]  Jinwoo Cheon,et al.  Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. , 2005, Journal of the American Chemical Society.