Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways

Li, Nan; Zhang, Cheng-Xiang; Wang, Xiaoxing; Zhang, Liang; Ma, Xu; Zhou, Jia; Ju, Rui-Jun; Li, Xiuying; Zhao, Weiliang; Lü, Wan-Liang

doi:10.1016/j.biomaterials.2013.01.055

Cited by 90 publications

(56 citation statements)

References 34 publications

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“…An enhanced antioxidant capacity allows cancer cells to not a universal finding, and mitochondrial respiration impairment is not a fixed feature of cancer cells [41] . Although the glycolytic inhibitors targeting the Warburg effect have been investigated in various cancer types, the glycolytic inhibitors with the exception of 3-BP (a lactate analog) [18,19, , 3-BrOP (a 3-bromopyruvate derivative) [71][72][73][74] , and dichloroacetate (DCA) have demonstrated low efficacy in arresting tumor growth when used alone [99] ; these inhibitors include 2-deoxy-D-glucose (a glucose analog) [70,[100][101][102][103][104][105][106][107][108][109][110][111][112] , lonidamine (a derivative of indazole-3-carboxylic acid) [113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] , methyl jasmonate on HK , 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one on PFK [162]…”

Section: Initiation Of Metastasismentioning

confidence: 99%

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Lee¹

2015

WJBC

125

115

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Aerobic glycolysis, i.e. , the Warburg effect, may contribute to the aggressive phenotype of hepatocellular carcinoma. However, increasing evidence highlights the limitations of the Warburg effect, such as high mitochondrial respiration and low glycolysis rates in cancer cells. To explain such contradictory phenomena with regard to the Warburg effect, a metabolic interplay between glycolytic and oxidative cells was proposed, i.e. , the "reverse Warburg effect". Aerobic glycolysis may also occur in the stromal compartment that surrounds the tumor; thus, the stromal cells feed the cancer cells with lactate and this interaction prevents the creation of an acidic condition in the tumor microenvironment. This concept provides great heterogeneity in tumors, which makes the disease difficult to cure using a single agent. Understanding metabolic flexibility by lactate shuttles offers new perspectives to develop treatments that target the hypoxic tumor microenvironment and overcome the limitations of glycolytic inhibitors.

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Section: Initiation Of Metastasismentioning

confidence: 99%

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Lee¹

2015

WJBC

125

115

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“…To evaluate targeting effects in mice, multifunctional targeting DiR liposomes were used as a fluorescent probe [41]. Briefly, 18 male ICR mice were inoculated with GSCs as above.…”

Section: Methodsmentioning

confidence: 99%

Multifunctional targeting daunorubicin plus quinacrine liposomes, modified by wheat germ agglutinin and tamoxifen, for treating brain glioma and glioma stem cells

et al. 2014

Oncotarget

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Most anticancer drugs are not able to cross the blood-brain barrier (BBB) effectively while surgery and radiation therapy cannot eradicate brain glioma cells and glioma stem cells (GSCs), hence resulting in poor prognosis with high recurrence rates. In the present study, a kind of multifunctional targeting daunorubicin plus quinacrine liposomes was developed for treating brain glioma and GSCs. Evaluations were performed on in-vitro BBB model, murine glioma cells, GSCs, and GSCs bearing mice. Results showed that the multifunctional targeting daunorubicin plus quinacrine liposomes exhibited evident capabilities in crossing the BBB, in killing glioma cells and GSCs and in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced efficacy of the multifunctional targeting drugs-loaded liposomes could be due to the following aspects: evading the rapid elimination from blood circulation; crossing the BBB effectively; improving drug uptake by glioma cells and GSCs; down-regulating the overexpressed ABC transporters; inducing apoptosis of GSCs via up-regulating apoptotic receptor/ligand (Fas/Fasl), activating apoptotic enzymes (caspases 8, 9 and 3), activating pro-apoptotic proteins (Bax and Bok), activating tumor suppressor protein (P53) and suppressing anti-apoptotic proteins (Bcl-2 and Mcl-1). In conclusion, the multifunctional targeting daunorubicin plus quinacrine liposomes could be used as a potential therapy for treating brain glioma and GSCs.

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“…The conjugation between dequalinium and PEG 2000 -DSPE allowed dequalinium to present at the surface of the liposomes without being sterically hindered by PEG 2000 . DQA-PEG 2000 -DSPE was used in two separate studies involving mitochondria-targeting liposomes carrying either resveratrol [44] or lonidamine [45] in an effort to overcome multidrug resistance in a lung cancer model. Resveratrol, a polyphenol found in many plant species, has anticancer effects on various cancer cells in vitro and in vivo [46].…”

Section: Sub-micron Particlesmentioning

confidence: 99%

“…Lonidamine, an antitumor agent that has been used in clinical trials for a variety of cancers, can preferentially induce apoptosis in cancer cells by reducing cellular ATP. In this study, Lu’s group prepared targeting liposomes loaded with either lonidamine or epirubicin [45]. The targeting liposomes contained DQA-PEG 2000 -DSPE for mitochondrial targeting and TPGS 1000 for drug efflux inhibition.…”

Section: Sub-micron Particlesmentioning

confidence: 99%

Mitochondria-Targeting Particles

Wongrakpanich

Geary

Joiner

et al. 2014

Nanomedicine (Lond.)

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Mitochondria are a promising therapeutic target for the detection, prevention and treatment of various human diseases such as cancer, neurodegenerative diseases, ischemia-reperfusion injury, diabetes and obesity. To reach mitochondria, therapeutic molecules need to not only gain access to specific organs, but also to overcome multiple barriers such as the cell membrane and the outer and inner mitochondrial membranes. Cellular and mitochondrial barriers can be potentially overcome through the design of mitochondriotropic particulate carriers capable of transporting drug molecules selectively to mitochondria. These particulate carriers or vectors can be made from lipids (liposomes), biodegradable polymers, or metals, protecting the drug cargo from rapid elimination and degradation in vivo. Many formulations can be tailored to target mitochondria by the incorporation of mitochondriotropic agents onto the surface and can be manufactured to desired sizes and molecular charge. Here, we summarize recently reported strategies for delivering therapeutic molecules to mitochondria using various particle-based formulations.

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Development of targeting lonidamine liposomes that circumvent drug-resistant cancer by acting on mitochondrial signaling pathways

Cited by 90 publications

References 34 publications

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication

Multifunctional targeting daunorubicin plus quinacrine liposomes, modified by wheat germ agglutinin and tamoxifen, for treating brain glioma and glioma stem cells

Mitochondria-Targeting Particles

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