Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES

Fu, Zhenxiang; Du, Hongliang; Meng, Siyu; Yao, Mengjiao; Zhao, Pan; Li, Xiang; Zheng, Xin; Yuan, Zhengqiu; Yang, Hui; Cai, Kaiyong; Dai, Liangliang

doi:10.1016/j.mtbio.2022.100449

Cited by 3 publications

(3 citation statements)

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“…To the best of our knowledge, this report represents the first investigation into the pharmacokinetics of BPTES in living animals. Recent studies have reported that the antitumor and senolytic effects of BPTES and its analogs and NPs are rapidly increasing [ 14 , 21 , 22 , 23 , 24 , 25 ]; however, their in vivo mechanisms are not yet fully understood, partly due to the poor bioavailability of BPTES. PET with [ 11 C]BPTES could serve as a tool to better understand the tissue distribution, kinetics of uptake and clearance, and differential effects related to treatment, such as single-dose versus pre-loading.…”

Section: Discussionmentioning

confidence: 99%

“…To improve the bioavailability of BPTES, many BPTES analogs have been synthesized [ 19 , 20 , 21 , 22 ]. Further, BPTES nanoparticles (BPTES-NPs) were developed to considerably attenuate tumor growth in certain models [ 18 , 23 , 24 , 25 ]. Therefore, accurately measuring the concentration of BPTES itself as a lead compound in targeted sites or organs and determining its pharmacokinetics in vivo helps evaluate the pharmacological effects of BPTES and its analogs and NPs.…”

Section: Introductionmentioning

confidence: 99%

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The Glutaminase-1 Inhibitor [11C-carbony]BPTES: Synthesis and Positron Emission Tomography Study in Mice

et al. 2023

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Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a selective inhibitor of glutaminase-1 (GLS1), consequently inhibiting glutaminolysis. BPTES is known for its potent antitumor activity and plays a significant role in senescent cell removal. In this study, we synthesized [11C-carbonyl]BPTES ([11C]BPTES) as a positron emission tomography (PET) probe for the first time and assessed its biodistribution in mice using PET. [11C]BPTES was synthesized by the reaction of an amine precursor () with [11C-carbonyl]phenylacetyl acid anhydride ([11C]2), which was prepared from [11C]CO2 and benzyl magnesium chloride, followed by in situ treatment with isobutyl chloroformate. The decay-corrected isolated radiochemical yield of [11C]BPTES was 9.5% (based on [11C]CO2) during a synthesis time of 40 min. A PET study with [11C]BPTES showed high uptake levels of radioactivity in the liver, kidney, and small intestine of mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Glutaminase-1 Inhibitor [11C-carbony]BPTES: Synthesis and Positron Emission Tomography Study in Mice

et al. 2023

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“…15 The strategy of starving therapy can be categorized into three modes of action: (1) effective reduction of nutrient supply to tumor tissues by inhibiting the formation of tumor blood vessels, which serve as channels for nutrient uptake and blood metastasis; 15 (2) utilization of microspheres and hydrogels as embolic agents to block blood supply arteries, preventing the transport of nutrients and oxygen; 16 and (3) employing drugs or enzymes, such as lornidamine or glucose oxidase (GOx), to disrupt the energy metabolism pathways of cancer cells, proving to be an effective strategy for starving therapy in cancer treatment. 17 Based on previous research, the specific catalytic action of GOx on substrates can rapidly reduce glucose concentrations in cancer cells, leading to cell death. 18 Consequently, the intracellular glucose consumption caused by GOx is expected to hinder the primary energy supply of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Glutathione-Responsive Organosilica Hybrid Nanosystems for Targeted Dual-Starvation Therapy in Luminal Breast Cancer

Ding,

Liu,

Liu

et al. 2023

Mol. Pharmaceutics

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Starvation therapy is an innovative approach in cancer treatment aimed at depriving cancer cells of necessary resources by impeding tumor angiogenesis or blocking the energy supply. In addition to the commonly observed anaerobic glycolysis energy supply mode, adipocyte-rich tumor tissue triggers the fatty acid energy supply pathway, which fuels the proliferation and metastasis of cancer cells. To completely disrupt these dual-energysupply pathways, we developed an exceptional nanoreactor. This nanoreactor consisted of yolk−shell mesoporous organosilica nanoparticles (YSMONs) loaded with a fatty acid transport inhibitor (Dox), conjugated with a luminal breast-cancer-specific targeting aptamer, and integrated with a glucose oxidation catalyst (GOx). Upon reaching cancer cells with the assistance of the aptamer, the nanoreactor underwent a structural collapse of the shell triggered by the high concentration of glutathione within cancer cells. This collapse led to the release of GOx and Dox, achieving targeted delivery and exhibiting significant efficacy in starving therapy. Additionally, the byproducts of glucose metabolism, gluconic acid and H 2 O 2 , enhanced the acidity and reactive oxygen species levels of the intracellular microenvironment, inducing oxidative damage to cancer cells. Simultaneously, released Dox acted as a potent broad-spectrum anticancer drug, inhibiting the activity of carnitine palmitoyltransferase 1A and exerting marked effects. Combining these effects ensures high anticancer efficiency, and the "dual-starvation" nanoreactor has the potential to establish a novel synergistic therapy paradigm with considerable clinical significance. Furthermore, this approach minimizes damage to normal organs, making it highly valuable in the field of cancer treatment.

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A Multichannel Metabolic Pathway Interference Strategy for Complete Energy Depletion‐Mediated Cancer Therapy

Ding,

Wei,

Fang

et al. 2024

Adv Funct Materials

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Hydrogen sulfide (H2S) is being progressively integrated as an emerging inhibitor of the electron transport chain in energy interference‐based tumor therapy. However, metabolic reprogramming in cancer cells causes both oxidative phosphorylation (OXPHOS) and glycolysis to occur simultaneously, which contributes to the ineffective therapeutic effect of blocking a single pathway. To achieve complete suppression of energy production, an inorganic H2S donor ZnS@ZIF‐8@CaP nanoparticle (ZSZC NP) carrying Ca and Zn is constructed for achieving simultaneous interference of OXPHOS and glycolysis. The core–shell ZSZC nanoparticles can break down in the tumor microenvironment. This leads to a sustained H2S release and calcium overload to disrupt the normal functioning of mitochondria by inhibiting the expression of cytochrome c and causing damage to mitochondrial membrane potential. Meanwhile, the presence of Zn2+ hinders the typical process of glycolysis by impeding the functioning of lactate dehydrogenase and glyceraldehyde‐3‐phosphate dehydrogenase. The synchronous interference of OXPHOS and glycolysis hampers the energy supply to cancer cells. Additionally, H2S and calcium overload can expedite tumor necrosis in vivo by inducing cellular acidification and calcification. Therefore, this energy‐blocking strategy will completely deplete the energy reserves of cancer cells and provide new insights for exploring bioenergetic inhibition as a treatment approach.

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Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES

Cited by 3 publications

References 50 publications

The Glutaminase-1 Inhibitor [11C-carbony]BPTES: Synthesis and Positron Emission Tomography Study in Mice

The Glutaminase-1 Inhibitor [11C-carbony]BPTES: Synthesis and Positron Emission Tomography Study in Mice

Glutathione-Responsive Organosilica Hybrid Nanosystems for Targeted Dual-Starvation Therapy in Luminal Breast Cancer

A Multichannel Metabolic Pathway Interference Strategy for Complete Energy Depletion‐Mediated Cancer Therapy

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