HER2 monoclonal antibody conjugated RNase-A-associated CdTe quantum dots for targeted imaging and therapy of gastric cancer.

Successful development of safe and effective nanoprobes for targeted imaging and selective therapy of in-situ gastric cancer is a great challenge. Herein, one kind of multifunctional HER2 monoclonal antibody conjugated RNase A-associated CdTe quantum dot cluster (HER2-RQDs) nanoprobes was prepared, its cytotoxicity was evaluated. Subcutaneous gastric cancer nude mouse models and in-situ gastric cancer SCID mouse models were established, and were intravenously injected HER2-RQDs nanoprobes, the bio-distribution and therapeutic effects of HER2-RQDs in vivo were evaluated. Results showed that HER2-RQDs nanoprobes could selectively kill gastric cancer MGC803 cells, could target imaging subcutaneous gastric cancer cells at 3 h post-injection, and in-situ gastric cancer cells at 6 h post-injection, and could inhibit the growth of gastric cancer tissues and extended survival time of gastric cancer bearing mouse models, which is closely associated with destroying functional RNAs in cytoplasm by RNase A released from HER2-RQDs nanoprobes, preventing protein synthesis and inducing cell apoptosis. High-performance HER2-RQDs nanoprobes exhibit great potential in applications such as in-situ gastric cancer targeted imaging, and selective therapy in the near future.

[1]  R. Bast,et al.  Serum levels of HER‐2 neu (C‐erbB‐2) correlate with overexpression of p185neu in human ovarian cancer , 1993, Cancer.

[2]  Liangzhu Feng,et al.  Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. , 2011, ACS nano.

[3]  Guido Kroemer,et al.  Caspase-independent cell death , 2005, Nature Medicine.

[4]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[5]  D. Newton,et al.  Construction of ribonuclease-antibody conjugates for selective cytotoxicity. , 2000, Methods in molecular medicine.

[6]  W. Hauswirth,et al.  Ribozyme gene therapy: applications for molecular medicine. , 2001, Trends in molecular medicine.

[7]  D. M. Parkin,et al.  Corrigendum to “Cancer burden in the year 2000. The global picture” [European Journal of Cancer,37(Suppl. 8) (2001) S4–S66] , 2003 .

[8]  M. Moasser The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis , 2007, Oncogene.

[9]  Shouwu Guo,et al.  Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy , 2011, Theranostics.

[10]  D. Parkin International variation , 2004, Oncogene.

[11]  S. Pathak,et al.  Hydroxylated quantum dots as luminescent probes for in situ hybridization. , 2001, Journal of the American Chemical Society.

[12]  L. Hertle,et al.  Cox-2 and Her2/neu co-expression in invasive bladder cancer. , 2005, International journal of oncology.

[13]  S. Altman,et al.  RNA enzyme-directed gene therapy. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[15]  R. Chaganti,et al.  ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix. , 1994, Cancer research.

[16]  Monty Liong,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. , 2008, ACS nano.

[17]  A. Ganguli,et al.  Enhanced functionalization of Mn2O3@SiO2 core-shell nanostructures , 2011, Nanoscale research letters.

[18]  D. Cui,et al.  A multifunctional ribonuclease-A-conjugated CdTe quantum dot cluster nanosystem for synchronous cancer imaging and therapy. , 2010, Small.

[19]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[20]  S. Cha,et al.  HER‐2/neu expression: A major prognostic factor in endometrial cancer , 1993, Gynecologic oncology.

[21]  Huajian Gao,et al.  A microarray-based gastric carcinoma prewarning system. , 2005, World journal of gastroenterology.

[22]  A. Neugut,et al.  Epidemiology of gastric cancer. , 2006, World journal of gastroenterology.

[23]  A. El‐Naggar,et al.  HER-2/neu oncogene characterization in head and neck squamous cell carcinoma. , 1995, Archives of otolaryngology--head & neck surgery.

[24]  S. Chiou,et al.  Survivin - an anti-apoptosis protein: its biological roles and implications for cancer and beyond. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[25]  K. Preissner,et al.  RNase therapy assessed by magnetic resonance imaging reduces cerebral edema and infarction size in acute stroke. , 2009, Current neurovascular research.

[26]  Daxiang Cui,et al.  Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy. , 2011, Biomaterials.

[27]  G. Sauter,et al.  Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus , 2007, Modern Pathology.

[28]  H. Maeda The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. , 2001, Advances in enzyme regulation.

[29]  M. Bruchez,et al.  Optical coding of mammalian cells using semiconductor quantum dots. , 2004, Analytical biochemistry.

[30]  T. Yamane,et al.  Protein Overexpression and Gene Amplification of c-erbB-2 in Pulmonary Carcinomas: A Comparative Immunohistochemical and Fluorescence In Situ Hybridization Study , 2001, Modern Pathology.

[31]  Hari Singh Nalwa,et al.  Medical applications of nanoparticles in biological imaging, cell labeling, antimicrobial agents, and anticancer nanodrugs. , 2011, Journal of biomedical nanotechnology.

[32]  Igor L. Medintz,et al.  Luminescent quantum dots in immunoassays , 2006, Analytical and bioanalytical chemistry.

[33]  W. Scheithauer,et al.  HER 2/neu protein expression in colorectal cancer , 2006, BMC Cancer.

[34]  Kan Wang,et al.  BRCAA1 monoclonal antibody conjugated fluorescent magnetic nanoparticles for in vivo targeted magnetofluorescent imaging of gastric cancer , 2011, Journal of nanobiotechnology.

[35]  Jeffrey I. Zink,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery , 2010, BiOS.

[36]  Daxiang Cui,et al.  Dual Phase‐Controlled Synthesis of Uniform Lanthanide‐Doped NaGdF4 Upconversion Nanocrystals Via an OA/Ionic Liquid Two‐Phase System for In Vivo Dual‐Modality Imaging , 2011 .

[37]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[38]  Jing Lin,et al.  Photosensitizer-conjugated magnetic nanoparticles for in vivo simultaneous magnetofluorescent imaging and targeting therapy. , 2011, Biomaterials.

[39]  D. Newton,et al.  Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase: evidence for cytotoxic mechanisms different from inhibition of protein synthesis. , 2000, Cancer research.

[40]  Marc D Feldman,et al.  Small multifunctional nanoclusters (nanoroses) for targeted cellular imaging and therapy. , 2009, ACS nano.

[41]  Kan Wang,et al.  Biocompatibility of hydrophilic silica-coated CdTe quantum dots and magnetic nanoparticles , 2011, Nanoscale research letters.

[42]  D. Cui,et al.  Gene Expression Profiles of Rodent Atrophic Gastritis Induced By Hot and Salt Water , 2011 .

[43]  F. Bray,et al.  Cancer burden in the year 2000. The global picture. , 2001, European journal of cancer.

[44]  R. Hoffman,et al.  Nude mouse metastatic models of human stomach cancer constructed using orthotopic implantation of histologically intact tissue. , 1993, Cancer research.

[45]  Jin Wu,et al.  The photoluminescence, drug delivery and imaging properties of multifunctional Eu3+/Gd3+ dual-doped hydroxyapatite nanorods. , 2011, Biomaterials.

[46]  Y. Yarden The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. , 2001, European journal of cancer.

[47]  G. Molema,et al.  Preparation and Functional Evaluation of RGD-Modified Proteins as r v â 3 Integrin Directed Therapeutics , 2022 .

[48]  Ick Chan Kwon,et al.  New Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy , 2009 .

[49]  S. Nie,et al.  Nanotechnology applications in cancer. , 2007, Annual review of biomedical engineering.

[50]  A. Jimeno,et al.  HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[51]  Grietje Molema,et al.  Preparation and functional evaluation of RGD-modified proteins as alpha(v)beta(3) integrin directed therapeutics. , 2002, Bioconjugate chemistry.

[52]  Igor L. Medintz,et al.  Fluorescence resonance energy transfer between quantum dot donors and dye-labeled protein acceptors. , 2003, Journal of the American Chemical Society.

[53]  S. Nie,et al.  Luminescent quantum dots for multiplexed biological detection and imaging. , 2002, Current opinion in biotechnology.

[54]  Dale M. Willard,et al.  CdSe−ZnS Quantum Dots as Resonance Energy Transfer Donors in a Model Protein−Protein Binding Assay , 2001 .

[55]  Adela C. Bonoiu,et al.  Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons , 2009, Proceedings of the National Academy of Sciences.

[56]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.