A novel dual-targeted rosiglitazone-loaded nanoparticle for the prevention of diet-induced obesity via the browning of white adipose tissue

Hiradate, Ryu; Khalil, Ikramy A.; Matsuda, Aya; Sasaki, Mika; Hida, Kyoko; Harashima, Hideyoshi

doi:10.1016/j.jconrel.2020.10.002

Cited by 32 publications

(21 citation statements)

References 49 publications

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“…2 The currently available strategies for treating obesity mostly focus on pharmacological therapy, reducing energy intake, and promoting energy expenditure via physical exercise as well as bariatric surgery and liposuction. 3,4 However, these therapeutics usually have unpleasant side effects that can jeopardize organs, including the intestines, liver, and kidneys. Therefore, alternative strategies for targeting energy-expenditure pathways are in urgent need.…”

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confidence: 99%

“…Mounting evidence indicates that the obesity-induced alteration of white adipose tissue (WAT) function facilitates the development of obesity-related comorbidities, such as type II diabetes and cardiovascular disease, threatening patient health, which results in a tremendous burden on the public healthcare system . The currently available strategies for treating obesity mostly focus on pharmacological therapy, reducing energy intake, and promoting energy expenditure via physical exercise as well as bariatric surgery and liposuction. , However, these therapeutics usually have unpleasant side effects that can jeopardize organs, including the intestines, liver, and kidneys. Therefore, alternative strategies for targeting energy-expenditure pathways are in urgent need …”

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confidence: 99%

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Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy

Chen

Gao

et al. 2021

ACS Nano

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The targeted delivery of phytochemicals that promote energy expenditure for obesity therapy remains a challenge. This study assembled a functionalized adipo-8 aptamer loaded with allicin using isothermal rolling-circle techniques to form a synergistic adipocyte-targeted binarydrug delivery system for treating obesity. The functionalized adipo-8 aptamer efficiently protected allicin from adsorption, showing significant potential to encapsulate, transport, and release molecular cargos into white adipose tissue. Introducing the negatively charged allicin, a phytochemical able to induce adipose tissue browning, reduced the diameters of DNAnanoflower from 770 to 380 nm and increased cellular uptake efficiency up to 118.7%. The intracellular distribution observed via confocal microscopy confirmed the successful receptor recognition mediated by aptamers in the DNA-nanoflower-allicin (NFA) framework as well as its excellent stability to escape from lysosomes. In vivo results demonstrated that subcutaneous administration of NFA effectively promoted adipocyte browning and systematic energy expenditure with minimal side effects. Furthermore, the G-quadruplex in the mitochondrial uncoupling protein-1 promoter was found to be an interactive allicin target for regulating thermogenesis to combat obesity.

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confidence: 99%

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confidence: 99%

Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy

Chen

Gao

et al. 2021

ACS Nano

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“…Taking WAT as an anti-obesity target transforming it into brown-like adipocytes (browning) and increasing human energy consumption is considered to be a very promising way to achieve anti-obesity [ 171 , 172 , 173 ]. It has been proved that several substances can promote browning to increase thermogenesis, such as β3-adrenoceptor agonist, thyroid hormone T3, rosiglitazone (ROSI), bile acid, fucoxanthin, curcumin, and so on [ 165 , 174 , 175 , 176 ]. Gelatin, gold nanoparticles, and caffeine can promote fat decomposition [ 177 , 178 , 179 ].…”

Section: The Main Delivery Methods Of Anti-obesity Drugs and Development Of New Anti-obesity Agentsmentioning

confidence: 99%

“…ROSI is a kind of PPARγ activator, which can enhance the sensitivity of skeletal muscle, liver, and AT to insulin, and it has been used to treat diabetics [ 187 ]. Recent studies have shown that it also has the effect of browning [ 175 ]. However, taking ROSI also has a potential risk of cardiovascular disease [ 203 ].…”

Section: Tdds For Anti-obesity Agentsmentioning

confidence: 99%

Transdermal Drug Delivery Systems and Their Use in Obesity Treatment

Fang

2021

IJMS

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Transdermal drug delivery (TDD) has recently emerged as an effective alternative to oral and injection administration because of its less invasiveness, low rejection rate, and excellent ease of administration. TDD has made an important contribution to medical practice such as diabetes, hemorrhoids, arthritis, migraine, and schizophrenia treatment, but has yet to fully achieve its potential in the treatment of obesity. Obesity has reached epidemic proportions globally and posed a significant threat to human health. Various approaches, including oral and injection administration have widely been used in clinical setting for obesity treatment. However, these traditional options remain ineffective and inconvenient, and carry risks of adverse effects. Therefore, alternative and advanced drug delivery strategies with higher efficacy and less toxicity such as TDD are urgently required for obesity treatment. This review summarizes current TDD technology, and the main anti-obesity drug delivery system. This review also provides insights into various anti-obesity drugs under study with a focus on the recent developments of TDD system for enhanced anti-obesity drug delivery. Although most of presented studies stay in animal stage, the application of TDD in anti-obesity drugs would have a significant impact on bringing safe and effective therapies to obese patients in the future.

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“…This improved ATS9R complex showed robust uptake by prohibitin in mouse adipocytes, delivering a short hairpin RNA for the fatty acid binding protein 4, all while avoiding liver uptake. Other publications support the use of an ATS/ATS9R NP in mice [ 32 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Divergence of Chemerin Reduction by an ATS9R Nanoparticle Targeting Adipose Tissue In Vitro vs. In Vivo in the Rat

et al. 2022

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Nanoparticles (NPs) can enable delivery of a drug to a targeted tissue. Previous studies have shown that an NP utilizing an adipose targeting sequence (ATS) peptide in conjunction with a drug can selectively deliver the drug to mouse adipose tissues, using the prohibitin protein expressed in adipose tissue as the target of the ATS. Adipose tissue is a major source of the adipokine chemerin, a prohypertensive protein. Liver-derived chemerin, the largest source of circulating chemerin, is biologically inactive in blood pressure regulation. Our goal is to understand if chemerin produced in adipose tissue contributes to blood pressure/hypertension. We hypothesize the ATS drug delivery system could be used specifically to reduce the levels of adipose tissue-derived chemerin. We created an NP consisting of an antisense oligonucleotide (ASO) against chemerin and a FITC-labeled ATS with a nine arginine sequence (ATS9R). In vitro studies showed that the ASO is functional when incorporated into an NP with ATS9R as it reduced chemerin mRNA expression in isolated epidydimal (Epi) and retroperitoneal (RP) fat adipocytes from Dahl SS rats. This same NP reduced chemerin in isolated whole fats. However, this NP was unable to selectively deliver the ASO to adipose tissue in vivo; liver delivery was dominant. Varying NP doses, administration route, and the concentration of components constituting the NP showed no improvement in ASO delivery to fats vs. the liver. Further studies are therefore needed to develop the ATS9R system to deliver an ASO to adipose beds in rats.

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A novel dual-targeted rosiglitazone-loaded nanoparticle for the prevention of diet-induced obesity via the browning of white adipose tissue

Cited by 32 publications

References 49 publications

Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy

Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy

Transdermal Drug Delivery Systems and Their Use in Obesity Treatment

Divergence of Chemerin Reduction by an ATS9R Nanoparticle Targeting Adipose Tissue In Vitro vs. In Vivo in the Rat

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