An ATP-Responsive Codelivery System of Doxorubicin and MiR-34a To Synergistically Inhibit Cell Proliferation and Migration

Wang, Yudi; Chen, Jiawen; Liang, Xiao; Han, Haobo; Wang, Hao; Yang, Yan; Li, Quanshun

doi:10.1021/acs.molpharmaceut.7b00184

Cited by 35 publications

(23 citation statements)

References 48 publications

(65 reference statements)

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“…The migration ability of C6 cells in vitro was assessed by a 24-well transwell V R [28]. Briefly, C6 cells were resuspended and added into the upper chamber of a transwell chamber containing 180 lL of serum-free F10 medium at a density of 5 Â 10 4 cells.…”

Section: Inhibitory Effects On Vm Channels and Blocking Effects On Tumentioning

confidence: 99%

Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma

Xiao

Cheng

Xie

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Glioma is the most common primary malignant brain tumor with a poor prognosis. The application of chemotherapeutic drugs is limited due to the existence of blood-brain barrier and serious side effects. Liposomes have been proven to be a stable and useful drug delivery system for tumors. In this paper, WGA (wheat germ agglutinin) modified vinorelbine cationic liposomes had been successfully constructed for treating glioma. In the liposomes, WGA was modified on the liposomal surface for crossing the blood-brain barrier and increasing the targeting effects, 3-(N-(N 0 , N 0-dimethylaminoethane) carbamoyl) cholesterol (DC-Chol) was used as cationic material and vinorelbine was encapsulated in the aqueous core of liposomes to inhibit tumor metastasis and kill tumor cells. Studies were performed on C6 cells in vitro and were verified in brain glioma-bearing mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce C6 cells apoptosis, promote drugs across the blood-brain barrier, inhibit the metastasis of tumor cells and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate PI3K, MMP-2, MMP-9 and FAK to inhibit tumor metastasis. Results in vivo exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and exhibited low toxicity to blood system and major organs. Hence, WGA modified vinorelbine cationic liposomes might provide a safe and efficient therapy strategy for glioma.

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Section: Inhibitory Effects On Vm Channels and Blocking Effects On Tumentioning

confidence: 99%

Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma

Xiao

Cheng

Xie

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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“…DOX is a broad-spectrum antitumor drug that intercalates into DNA and prevents the process of transcription. The main effect of DOX is suppression of cell proliferation and migration, especially in cancer cells (12,13). It exhibits a potent cytotoxic effect, which can kill the tumor cells of various growth cycles (14).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Huang

Tan

et al. 2018

Oncol Rep

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Non-small cell lung cancer (NSCLC) is one of the mostly deadly malignancies in the world. Nucleolin is a multifunctional protein that mainly regulates ribosome biogenesis but also has other functions including modulating the transcription of mRNAs and repressing RNA polymerase II. Nucleolin is overexpressed in various cancer cells, including NSCLC cells. It can confer resistance to apoptosis and promote cell migration and blood vessel formation by directly taking part in various tumor signal transduction pathways. The activities of nucleolin are regulated mainly by intracellular localization and post-translational modifications, including phosphorylation, glycosylation, methylation, and ADP-ribosylation. Phosphorylation of nucleolin (P-nucleolin) in NSCLC cells is still not well characterized. In the present study, the levels of nucleolin and P-nucleolin were examined in lung tissue and cells and it was demonstrated that levels of the two forms of nucleolin were significantly increased in NSCLC compared with non-cancerous tissues and cells. In addition, it was demonstrated that high expression levels of nucleolin and P-nucleolin were significantly associated with poor overall survival of NSCLC patients. Doxorubicin (DOX) is a type of anthracycline that has been used in the treatment of various types of cancer, including NSCLC. Upregulation of nucleolin through exogenous expression of nucleolin promoted A549 cell proliferation and migration, while downregulation of nucleolin through expression of small interfering RNA-nucleolin attenuated A549 cell proliferation and migration. Following stimulation with DOX, A549 cell proliferation and migration decreased and the expression of P-nucleolin also decreased. In order to investigate whether P-nucleolin is indispensable to the proliferation and migration of NSCLC cells, a plasmid encoding mutant nucleolin, in which the phosphorylation site at threonine-76 was mutated to alanine, was constructed. Compared with the A549 cells transfected with wild-type nucleolin, P-nucleolin expression and cell proliferation and migration were significantly decreased in A549 cells transfected with mutant nucleolin. These results indicate that targeting P-nucleolin may be a promising strategy for treating NSCLC patients.

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“…Apoptosis has been reported to be one of the primary mechanisms of action of DOX (Wang et al, 2017 ). Incubated with HepG-2 cells at a equivalent concentration of 10 μg/mL DOX for 48 h (Yang et al, 2016 ), the effect of free DOX, DOX loaded PLA-PEG-PLA-18K, and PEG-DiHyd-PLA-18K micelles on apoptosis was shown in Figure 10 , the total apoptosis ratio of DOX-loaded PLA-PEG-PLA-18K micelles was about 38% (a sum of the early apoptosis ratio of 26.89% and the late apoptosis ratio of 10.62%).…”

Section: Resultsmentioning

confidence: 99%

Hydrazone-Containing Triblock Copolymeric Micelles for pH-Controlled Drug Delivery

Liu

et al. 2018

Front. Pharmacol.

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In this study, the structure–activity relationship of amphiphilic block copolymer micelles as nanosized drug delivery system was revealed. Firstly, a biodegradable triblock polymers PEG-DiHyd-PLA containing hydrazone bond was synthesized through the ring-opening polymerization. In this method, PEG-DiHyd-Phenol was used as the initiator and L-lactide as the monomer. Then, the polymeric micelles were formed and used as nano-drug carriers with pH sensitivity. The structure and composition of the polymer were characterized by infrared (IR), nuclear magnetic resonance (1H-NMR), and gel permeation chromatography (GPC), we characterized the self-assembling process of the triblock polymers and the pH sensitivity of the micelles by the means of transmission electron microscopy (TEM), dynamic light scattering method (DLS). Doxorubicin (DOX) acts as the model drug, and we researched the capacities of drug loading and release in vitro of the micelles. MTT experiments showed that the blank micelles of PEG-DiHyd-PLA were not cytotoxic to tumor cells (HepG-2, MCF-7) and normal cell (L-02 cells), but the DOX loaded ones displayed more toxicity than the ones without hydrazone, which was consistent to the further confocal laser scanning microscopy and flow cytometry study.

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An ATP-Responsive Codelivery System of Doxorubicin and MiR-34a To Synergistically Inhibit Cell Proliferation and Migration

Cited by 35 publications

References 48 publications

Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma

Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Hydrazone-Containing Triblock Copolymeric Micelles for pH-Controlled Drug Delivery

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