image: Self-assembled SA-V6/PAHSA nanovesicles traverse the intestinal barrier to target metabolic tissues. Structural visualization showing stearic acid tails and PAHSAs stabilizing hexavanadate clusters. Dual therapeutic actions, PTP1B inhibition enhances insulin receptor phosphorylation and GPR120 activation in adipose tissue suppresses proinflammatory factor secretion. Restored metabolic homeostasis in HFD mice evidenced by normalized glucose curves and lipid profiles.
Credit: Polyoxometalates, Tsinghua University Press
Obesity-driven metabolic dysfunction and chronic inflammation present major therapeutic hurdles, exacerbated by the limited bioavailability and rapid degradation of endogenous lipid mediators like anti-inflammatory fatty acid esters, such as palmitic acid hydroxystearic acids (PAHSAs). Polyoxometalate-based nanoplatforms offer a promising strategy to overcome these delivery barriers and synergistically target multiple pathways.
A research team led by Kun Chen from the South China University of Technology developed stearic acid-modified hexavanadate vesicles (SA-V6) loaded with PAHSA lipids (SA-V6/PAHSA) to simultaneously combat insulin resistance and inflammation in obesity. Their study demonstrates how this hybrid nanocarrier enhances therapeutic efficacy by stabilizing fragile bioactive compounds and enabling tissue-specific delivery.
The team published their study in Polyoxometalates on July 11, 2025.
“Our SA-V6 platform acts as a molecular shield against enzymatic degradation while facilitating dual activation of GPR40/GPR120 receptors by PAHSA in metabolic tissues,” explained Kun Chen, corresponding author and associate professor at the School of Emerging Soft Matter for Soft Matter Science and Technology. “This approach not only extends PAHSA half-life but also creates synergistic effects unattainable with free compounds.”
In addition, hexavanadate clusters functionalized with stearic acid co-self-assemble with PAHSA into nanovesicles. Hydrophilic vanadate cores exposed on the vesicle surface enable enzyme inhibition, while hydrophobic stearate tails facilitate membrane penetration. The SA-V6/PAHSA platform leveraged polyoxometalate activity to suppress protein tyrosine phosphatase 1B (PTP1B) which plays an important role in the negative regulation of insulin signaling pathway.
The research team outlines the progress made in graphene-based sensors designed to measure a variety of different signals from the body. “The self-assembled SA-V6/PAHSA platform solve two critical problems plaguing obesity treatment. First, their vanadate core inhibits PTP1B, an enzyme that disrupts insulin signaling. Second, they protect and deliver fragile PAHSAs, natural lipids that activate the GPR120 receptor to suppress inflammation. This synergy restores metabolic homeostasis without weight gain—a critical limitation of PPARγ agonists.,” Kun Chen said.
Hexavanadate cores inhibit PTP1B to amplify insulin signaling, overcoming historical vanadium toxicity via lipid stabilization. PAHSA co-delivery activates GPR120 to suppress adipose TNF-α/IL-6 secretion, while boosting GLP-1 production and glucose-dependent insulin secretion. This dual payload generates powerful synergy. When administered orally to obese mice, SA-V6/PAHSA vesicles increased active GLP-1 and insulin secretion, normalized blood glucose, slashed pro-inflammatory cytokines in adipose tissue, and restored cholesterol balance without promoting weight gain. Treatment with SA-V6/PAHSA nanovesicles achieved higher insulin receptor activation through phosphatase blockade compared to vehicle treatment.
Crucially, the nanovesicles resist degradation in the gut, leveraging lipid raft-mediated uptake to accumulate in metabolic tissues. Their pH-stable architecture ensures cargo delivery to inflamed adipocytes where healing occurs at the molecular level. Kun chen said, “Our vesicles unlock both metabolic healing pathways at once through engineered polyoxovanadate-lipid hybrids that actively reshape cellular environments.”
Unlike injectable GLP-1 analogs, this platform resolves inflammation-induced insulin resistance, the core pathology of metabolic syndrome. “Vanadium alone can sensitize cells to insulin but aggravates oxidative stress”, notes Chen. “PAHSAs alone reduce inflammation but degrade rapidly. Together in our nanostructure, they become greater than the sum—calming inflamed tissue while restoring glucose homeostasis.”
This trajectory transforms nanovesicles from drug carriers to intelligent metabolic modulators, potentially rendering daily injections obsolete and addressing obesity’s root causes rather than symptoms. The fusion of polyoxometalate chemistry and lipid biology exemplifies the next frontier in translational nanomedicine – where materials don’t just deliver therapy, they become the therapy.
Other contributors include Pengyu Wu, Pengcheng Cui, and Yingying Wang from South China Advanced Institute for Soft Matter Science and Technology and School of Emergent Soft Matter at South China University of Technology in Guangzhou, China.
This work was supported by National Natural Science Foundation of China (22101086) and Guangzhou Science and Technology Plan Project (2025A04J3974).
About the Authors
Dr. Kun Chen is a key faculty member at the School of Emerging Soft Matter, South China University of Technology. Her research centers on the design, synthesis, and multiscale structural manipulation of soft matter functional materials, with a focus on intelligent responsive mechanisms for applications in biomedicine and advanced devices. She specifically targets fundamental theoretical breakthroughs and practical applications of polyoxometalate- and polymer-based functional and intelligent materials to address core challenges in healthcare and flexible electronics. Until now, she has published more than 60 papers in Polyoxometalates and other journals, presided over 4 national/provincial scientific research projects, owns 10 invention patents. For more information, please pay attention to her research homepage https://www2.scut.edu.cn/aismst/2018/0716/c21554a275805/page.htm.
About Polyoxometalates
Polyoxometalates (POM) is a peer-reviewed, open-access and interdisciplinary journal, published quarterly by Tsinghua University Press, released exclusively on SciOpen. POM publishes original high-quality research papers and significant review articles that focus on cutting-edge advancements in polyoxometalates, and clusters of metals, metal oxides and chalcogenides. It is dedicated to exploring all topical areas, ranging from basic aspects of the science of polyoxometalates, and clusters of metals, metal oxides and chalcogenides to practical applications of such materials. The journal is indexed by Scopus (CiteScore 2024 = 14.7), Ei Compendex, CAS, and DOAJ.
Journal
Polyoxometalates
Article Title
Stearic acid-modified hexavanadate vesicles loaded with hydroxy fatty acid esters synergistically improve obesity-related metabolic disorders and inflammation
Article Publication Date
11-Jul-2025