پديدآورندگان :
Abrishami Amir Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran , Bahrami Ahmad Reza Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran , Nekooei Sirous Department of Radiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran , Sh. Saljooghi Amir Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran, Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran , M. Matin Maryam matin@um.ac.ir Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran, Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran . saljooghi@um.ac.ir
كليدواژه :
colorectal cancer , Targeted therapy , Theranostic , pH , sensitive gatekeeper , Magnetic Quantum dots
چكيده فارسي :
Aim and Background: Quantum dots (QDs) known as novel semiconductor nanocrystals with excellent fluorescence properties can be combined with Gd3+ paramagnetic ion as T1 MR contrast agent and used as dual-modal imaging probe. Designing theranostic drug delivery systems (DDSs) with QD core and mesoporous silica shell (QD@MSN) that could carry chemotherapeutic drugs presents great potential for simultaneous cancer therapy and imaging. By controlled drug release at tumor region via pH responsive gatekeepers such as gold nanoparticles (AuNPs), active targeted nanocarriers armed with aptamers could significantly optimize delivery performance to cancer cells. Methods: Synthesis of QDs containing Gd3+ was accomplished in organic phase followed by mesoporous silica coating for transferring to aqueous phase. The backbone (QD@MSNs) was used as epirubicin (EPI) carrier. After AuNPs capping and polyethylene glycol (PEG) incorporation, epithelial cell adhesion molecule (EpCAM) aptamers were conjugated for active targeting to colorectal cancer (CRC) cells. Hemolysis and MTT assays were performed to assess biocompatibility and cytotoxicity, respectively. Afterwards, anti-tumor efficiency as well as biosafety of prepared nanocarriers were evaluated in vivo. Three imaging modalities based on fluorescence, magnetic resonance and computed tomography were employed to track accumulation of targeted nanoparticles in tumor. Results and discussion: Higher drug release from prepared nanocarriers (size 70 nm) in acidic pH confirmed the controlled release. Hemolysis assay showed biocompatibility enhancement after PEGylation, and MTT results confirmed significant higher cytotoxicity of QD@MSNs-EPI-Au-PEG-Apt on HT-29 cells compared to CHO EpCAM negative cells. In vivo experiments indicated targeted delivery and nanoparticle traceability by various imaging modalities. Conclusion: Consequently, the QD@MSNs-EPI-Au-PEG-Apt could serve as a theranostic system which carried EPI selectively to CRC cells.
