Neovasculature and circulating tumor cells dual-targeting nanoparticles for the treatment of the highly-invasive breast cancer

Autor: Dan Wei, Jun Chen, Tianze Jiang, Qianqian Zhu, Xunbin Wei, Ting Kang, Jingxian Feng, Xiaoling Gao, Jianhui Yao
Rok vydání: 2017
Předmět:
Pathology
Lung Neoplasms
Cell
02 engineering and technology
Metastasis
Rats
Sprague-Dawley
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Circulating tumor cell
Breast
Lung
Drug Carriers
Mice
Inbred BALB C
Neovascularization
Pathologic
medicine.diagnostic_test
Epithelial cell adhesion molecule
Aptamers
Nucleotide
Epithelial Cell Adhesion Molecule
Neoplastic Cells
Circulating
021001 nanoscience & nanotechnology
Primary tumor
medicine.anatomical_structure
Paclitaxel
Mechanics of Materials
030220 oncology & carcinogenesis
Drug delivery
Female
0210 nano-technology
Oligopeptides
medicine.medical_specialty
Biophysics
Mice
Nude
Breast Neoplasms
Bioengineering
Flow cytometry
Biomaterials
03 medical and health sciences
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Neoplasm Invasiveness
business.industry
medicine.disease
Antineoplastic Agents
Phytogenic
chemistry
Ceramics and Composites
Cancer research
Nanoparticles
business
Zdroj: Biomaterials. 113:1-17
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2016.10.033
Popis: Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as ‘seeds’. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect. Enhanced cellular uptake, cell apoptosis-induction and cell-viability inhibition efficiency of the peptide and aptamer dual-functionalized nanoparticles (dTNP) were observed in both human umbilical vein endothelial cells (HUVEC) and 4T1 cells in vitro . Using cone-and-plate viscometer to create venous flow velocity, dTNP was also found to be able to capture CTCs under shear stress. The CTC-targeting and neutralization effect of dTNP in bloodstream and 4T1-GFP cell-derived lung metastasis mice model was confirmed via in vivo flow cytometry (IVFC), intravital imaging and confocal microscopy analysis. As a result, the orthotropic breast tumor-bearing mice administrated with PTX-loaded dTNP exhibited the optimal therapeutic effect. Taken together, the findings here provided direct evidence that the tumor neovasculature and CTCs dual-targeting drug delivery system could provide a novel modality for the treatment of highly-invasive breast cancer.
Databáze: OpenAIRE
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