Polyetherimide-grafted Fe3O4@SiO2 nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging

Li, Tingting; Shen, Xue; Chen, Yin; Zhang, Chengchen; Yan, Jie; Yang, Hong; Wu, Chunhui; Zeng, Hongjun; Liu, Yiyao

doi:10.2147/ijn.s85095

Cited by 45 publications

(20 citation statements)

References 46 publications

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“…Distilled water and isotonic 0.9% NaCl were applied as positive and negative controls, respectively. The supernatant absorbance was measured at 540 nm using ELISA reader (Hiperion, microplate reader MPR4+) (Li et al 2015 ). The hemolysis percentage was calculated using the following equation: …”

Section: Methodsmentioning

confidence: 99%

Magnetic hyperthermia of breast cancer cells and MRI relaxometry with dendrimer-coated iron-oxide nanoparticles

et al. 2018

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BackgroundRecently, some studies have focused on dendrimer nanopolymers as a magnetic resonance imaging (MRI) contrast agent or a vehicle for gene and drug delivery. Considering the suitable properties of these materials, they are appropriate candidates for coating iron-oxide nanoparticles which are applied in magnetic hyperthermia. To the best of our knowledge, the novelty of this study is the investigation of fourth-generation dendrimer-coated iron-oxide nanoparticles (G4@IONPs) in magnetic hyperthermia and MRI.MethodsIONPs were synthesized via co-precipitation and coated with the fourth generation (G4) of polyamidoamine dendrimer. The cytotoxicity of G4@IONPs with different concentrations was assessed in a human breast cancer cell line (MCF7) and human fibroblast cell line (HDF1). Hemolysis and stability of G4@IONPs were investigated, and in addition, the interaction of these particles with MCF7 cells was assessed by Prussian blue staining. Heat generation and specific absorption rate (SAR) were calculated from measurement and simulation results at 200 and 300 kHz. MCF7 and HDF1 cells were incubated with G4@IONPs for 2 h and then put into the magnetic coil for 120 min. Relaxometry experiments were performed with different concentrations of G4@IONPs with T1- and T2-weighted MR images.ResultsThe TEM results showed that G4@IONPs were 10 ± 4 nm. The in vitro toxicity assessments showed that synthesized nanoparticles had low toxicity. The viability of MCF7 cells incubated with G4@IONPs decreased significantly after magnetic hyperthermia. In addition, MR imaging revealed that G4@IONPs improved transverse relaxivity (r2) significantly.ConclusionsOur results encouraged the future application of G4@IONPs in magnetic hyperthermia and MR imaging.

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Section: Methodsmentioning

confidence: 99%

Magnetic hyperthermia of breast cancer cells and MRI relaxometry with dendrimer-coated iron-oxide nanoparticles

et al. 2018

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“…A feasible target for RNAi therapeutics is vascular endothelial growth factor (VEGF), a vital regulatory cytokine secreted by cancer cells during angiogenesis 37,38 and important for tumor survival, growth, migration, and metastasis. [39][40][41] RNAi-mediated silencing of VEGF expression has been validated as a feasible and effective cancer treatment, [42][43][44] especially when combined with chemotherapeutic drugs within the same delivery system. 45 Feng et al 46 designed a core-shell type nanoparticle system embedded by vapreotide-modified polyethylene glycol phospholipid vapreotide to deliver VEGF siRNA and paclitaxel, resulting in enhanced tumor therapy efficacy through tumor-targeted delivery, cytotoxicity of paclitaxel, and VEGF downregulation by siRNA silencing.…”

Section: Introductionmentioning

confidence: 99%

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics

Shen¹,

Li²,

Chen³

et al. 2017

IJN

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Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe 3 O 4 nanocrystals, and doxorubicin (DOX) into biodegradable poly( d,l -lactic- co -glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T 2 -weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual-modality imaging in cancer treatment.

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“…More importantly, because of it negatively charged nature, free siRNA is unable to penetrate the cell membrane (Whitehead et al, 2009). To address this issue, a variety of carriers have been extensively utilized to facilitate the delivery of siRNA into cytoplasm (Shi et al, 2014; Dim et al, 2015; Li et al, 2015; Fitzgerald et al, 2016; Warashina et al, 2016). Among them, fluorescent quantum dots (QDs) have been investigated as potential carriers for the loading of gene molecules owing to their stable chemical properties and large surface area (Jung et al, 2010; Zhao et al, 2013; Wang et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Quantum Dots-siRNA Nanoplexes for Gene Silencing in Central Nervous System Tumor Cells

et al. 2017

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RNA interfering (RNAi) using short interfering RNA (siRNA) is becoming a promising approach for cancer gene therapy. However, owing to the lack of safe and efficient carriers, the application of RNAi for clinical use is still very limited. In this study, we have developed cadmium sulphoselenide/Zinc sulfide quantum dots (CdSSe/ZnS QDs)-based nanocarriers for in vitro gene delivery. These CdSSe/ZnS QDs are functionalized with polyethyleneimine (PEI) to form stable nanoplex (QD-PEI) and subsequently they are used for siRNA loading which specially targets human telomerase reverse transcriptase (TERT). High gene transfection efficiency (>80%) was achieved on two glioblastoma cell lines, U87 and U251. The gene expression level (49.99 ± 10.23% for U87, 43.28 ± 9.66% for U251) and protein expression level (51.58 ± 7.88% for U87, 50.69 ± 7.59% for U251) of TERT is observed to decrease substantially after transfecting the tumor cells for 48 h. More importantly, the silencing of TERT gene expression significantly suppressed the proliferation of glioblastoma cells. No obvious cytotoxicity from these QD-PEI nanoplexes were observed over at 10 times of the transfected doses. Based on these results, we envision that QDs engineered here can be used as a safe and efficient gene nanocarrier for siRNA delivery and a promising tool for future cancer gene therapy applications.

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Polyetherimide-grafted Fe3O4@SiO2 nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging

Cited by 45 publications

References 46 publications

Magnetic hyperthermia of breast cancer cells and MRI relaxometry with dendrimer-coated iron-oxide nanoparticles

Magnetic hyperthermia of breast cancer cells and MRI relaxometry with dendrimer-coated iron-oxide nanoparticles

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics

Quantum Dots-siRNA Nanoplexes for Gene Silencing in Central Nervous System Tumor Cells

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