Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo

Sun, Qi; Wang, Xiaoli; Cui, Chunying; Li, Jing; Wang, Yifan

doi:10.2147/ijn.s162939

Cited by 52 publications

(34 citation statements)

References 52 publications

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“…33 GO has been considered an ideal vector for gene delivery. 34,35 In this study, we demonstrated that GO-PEI was an effective nonviral carrier for miRNA delivery to suppress osteosarcoma cancer progression. GO bonded to PEI by electrostatic interactions and formed GO-PEI complexes with a positive charge (Figure 2).…”

Section: Discussionmentioning

confidence: 73%

<p>Efficient miRNA Inhibitor with GO-PEI Nanosheets for Osteosarcoma Suppression by Targeting PTEN</p>

Ou¹,

Lin²,

Song³

et al. 2020

IJN

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Background: Gene therapy is considered a novel way to treat osteosarcoma, and microRNAs are potential therapeutic targets for osteosarcoma. miR-214 has been found to promote osteosarcoma aggression and metastasis. Graphene oxide (GO) is widely used for gene delivery for the distinct physiochemical properties and minimal cytotoxicity. Methods: Polyethyleneimine (PEI)-functionalized GO complex was well-prepared and loaded with miR-214 inhibitor at different concentrations. The load efficacy was tested by gel retardation assay and the cy3-labeled fluorescence of cellular uptake. The experiments of wound healing, immunofluorescence staining, Western blot, qRT-PCR and immunohistochemical staining were performed to measure the inhibitory effect of the miR-214 inhibitor systematically released from the complexes against MG63, U2OS cells and xenograft tumors. Results: The systematic mechanistic elucidation of the efficient delivery of the miR-214 inhibitor by GO-PEI indicated that the inhibition of cellular miR-214 caused a decrease in osteosarcoma cell invasion and migration and an increase in apoptosis by targeting phosphatase and tensin homolog (PTEN). The synergistic combination of the GO-PEI-miR-214 inhibitor and CDDP chemotherapy showed significant cell death. In a xenograft mouse model, the GO-PEI-miR-214 inhibitor significantly inhibited tumor volume growth. Conclusion: This study indicates the potential of functionalized GO-PEI as a vehicle for miRNA inhibitor delivery to treat osteosarcoma with low toxicity and miR-214 can be a good target for osteosarcoma therapy.

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Section: Discussionmentioning

confidence: 73%

<p>Efficient miRNA Inhibitor with GO-PEI Nanosheets for Osteosarcoma Suppression by Targeting PTEN</p>

Ou¹,

Lin²,

Song³

et al. 2020

IJN

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“…The polyethylene glycol-diamine/R8-functionalized GO has been shown to effectively down-regulate c-Myc protein and EGFP expression [29]. The treatment with GO-poly-l-lysine hydrobromide/folic acid (GPF)/DOX/siRNA was able to silence gene expression and inhibit tumors by about 70% without exhibiting testable cytotoxicity; moreover, there was a decrease of 50% in vascular endothelial growth factor (VEGF), mRNA, and protein levels [30]. GO nanohybrids, used for the delivery of chemotherapeutic agent fluorouracil (FU) against breast cancer MCF7 cells, increased the protein levels of p53 and cleaved PARP proteins [31].…”

Section: Discussionmentioning

confidence: 99%

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

Caccamo¹,

Currò²,

Ientile³

et al. 2020

IJMS

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The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field.

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“…The samples were electrophoresed in 1% (w/v) agarose gel containing ethidium bromide (2 mg/ml) at a constant voltage of 120 V for 20 min. The results was observed under the UV transilluminator [17].…”

Section: Confirmation Of Sirna Encapsulation In Chnp's By Agarose Gelmentioning

confidence: 99%

DEVELOPMENT AND CHARACTERIZATION OF DOXORUBICIN AND siRNA ENCAPSULATED CHITOSAN NANOPARTICLES

Momin¹,

Gulbake²

2020

Int J App Pharm

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Objective: Chitosan nanoparticles (ChNP’s) have been widely studied for drug and gene delivery. In this study, we prepared ChNP’s for co-delivery of doxorubicin (DOX) and siRNA for cancer treatment. Methods: The ionic gelation method was used to develop ChNP’s. The positively charged DOX and negatively charged siRNA encapsulated into ChNP’s. The particle size and zeta potential of the developed ChNP’s were studied by particle size analyzer and morphology was examined by TEM. Encapsulation of DOX in ChNP’s was confirmed by FTIR spectroscopy. The encapsulation efficiency and in vitro release of DOX were studied by UV-Vis spectrophotometry. The siRNA loading into ChNP’s was confirmed by gel retardation assay. Results: The developed ChNP’s showed particle size ranged from 127±6.5 to 215±8.5 nm with zeta potential ranged from 16.5±0.3 to 25.8±0.3. Transmission Electron Micrograph showed DOX and siRNA encapsulated ChNP’s are polydisperse and spherical in nature. FTIR study confirmed the binding of DOX with ChNP’s with absorption peaks at 1016 cm-1,1316 cm-1, 1412 cm-1, 1645 cm-1 and 3370 cm-1. The TPP:Ch ratio 0.1:0.5 showed the highest encapsulation efficiency 69±3.24%, with initial burst release and then sustained or slow release of DOX. Agarose gel retardation study confirmed the encapsulation of siRNA in ChNP’s by retarded migration of siRNA-ChNP’s in comparison with naked siRNA. Conclusion: The developed ChNP’s successfully encapsulated the DOX and siRNA and showed the sustain release of DOX. In conclusion, our study shown that ChNP’s is having a potential of co-loading of DOX-siRNA as an efficient drug delivery system for the treatment of various cancers such as colorectal cancer, breast cancer etc.

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Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo

Cited by 52 publications

References 52 publications

<p>Efficient miRNA Inhibitor with GO-PEI Nanosheets for Osteosarcoma Suppression by Targeting PTEN</p>

<p>Efficient miRNA Inhibitor with GO-PEI Nanosheets for Osteosarcoma Suppression by Targeting PTEN</p>

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

DEVELOPMENT AND CHARACTERIZATION OF DOXORUBICIN AND siRNA ENCAPSULATED CHITOSAN NANOPARTICLES

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