POMs are a class of inorganic metal-oxygen cluster compounds with broad-spectrum antitumor potential. However, their strong hydrophilicity and poor lipophilicity result in insufficient cell membrane permeability, and high doses are required to achieve therapeutic effects, which severely limits their clinical application. To address this challenge, the research team proposes a covalent modification strategy: the construction of an amphipathic drug molecule PPT-POM-PPT by linking the hydrophobic anti-tumor drug Podophyllotoxin (PPT) with hydrophilic POMs. This molecule can self-assemble into nanoscale vesicles, serving dual functions as both a drug delivery carrier and an active component, significantly enhancing the lipophilicity and bioavailability of POMs.
By modifying the antitumor drug PPT with POMs, the amphiphilic drug molecule PPT-POM-PPT was successfully prepared, which exhibits the property of self-assembling into vesicles. These vesicles can effectively deliver the drug without the need for additional carrier materials, significantly enhancing the drug's stability and biocompatibility. Cytotoxicity experiments demonstrated that PPT-POM-PPT vesicles exhibit excellent anticancer activity against various tumor cells while showing low toxicity to normal cells. PPT-POM-PPT combined the dual antitumor advantages of PPT and POMs, achieving stronger tumor suppression. Its unique self-assembly capability allowed the vesicles to form spontaneously, avoiding potential risks associated with external carriers while ensuring efficient and accurate drug delivery.
The team published their research in Polyoxometalates on March 19, 2025.
"The newly synthesized amphiphilic drug, PPT-POM-PPT, demonstrated the ability to self-assemble into vesicles in aqueous solutions. Through transmission electron microscopy (TEM) and zeta potential analysis, it was found that these vesicles formed hollow spherical structures with negative charge. The vesicles featured a hydrophilic POMs terminal on the periphery and a hydrophobic PPT terminal on the interior, contributing to their unique properties." said Dejin Zang and Teng Liu, senior authors of the research paper, associate professors in the Shandong First Medical University & Shandong Academy of Medical Sciences.
The MTT assay revealed that the PPT-POM-PPT vesicles exhibited potent anti-cancer activity against H1299, A549, and Hep-G2 tumor cells. Notably, the vesicles demonstrated lower toxicity toward HEK293 normal cells, highlighting their potential for selective tumor targeting. The research team concluded that these vesicles significantly enhance cancer cell inhibition while ensuring safety for normal cells, achieving a synergistic therapeutic effect.
The research team emphasized that the PPT-POM-PPT vesicles offer a unique advantage by delivering drugs without the need for additional carrier materials, thereby improving drug stability and biocompatibility. Moreover, the vesicles integrate the anti-tumor effects of both PPT and POMs, enabling effective uptake by tumor cells and subsequent growth inhibition. This dual mechanism of action makes POMs a promising candidate for tumor therapy, laying a theoretical foundation for future clinical applications and opening up new avenues for cancer treatment.
Other contributors include Lingmei Li, Yixiang Song, Jinyu Liu, Quanfu Wang, Jiacheng Wu, Xiaochuan Lu, Dejin Zang, and Teng Liu from the School of Pharmaceutical Sciences & Institute of Materia Medica of Shandong First Medical University & Shandong Academy of Medical Sciences.
This work was supported by the Natural Science Foundation of China (No. 21801153), Natural Science Foundation of Shandong Province (No. ZR2023MB065), the Shandong Province Chinese Medicine Science and Technology Development Project (No. M-2022258), Young Scientist Development Foundation of Shandong First Medical University (No. 202201-002), and the Academic Promotion Program of Shandong First Medical University (No. 2019LJ003).
About the Authors
Dejin Zang obtained his PhD degree from University of Strasbourg in 2017. He is working as an associate professor at Shandong First Medical University & Shandong Academy of Medical Sciences, China. He is exploring the preparation of polyoxometalate complexes and their application in electrocatalytic organocatalytic reactions. His related achievements have been published in over 40 SCI papers in journals such as Appl. Catal. B Environ., Adv. Energy Mater., Nano Res., Angew. Chem. Int. Ed., Sensor Actuat B-Chem., ACS Appl. Mater. Interfaces, and Chinese Chem. Lett.
Teng Liu obtained her PhD degree from Shandong University in China in 2013. She has been working at Shandong First Medical University & Shandong Academy of Medical Sciences, China. Her research interests are the structural design and mechanism of polyoxometalates, the design of functional drug molecules of polyoxometalates. Her related achievements have been published in over 30 SCI papers in journals such as Rare Met., J. Colloid Interface Sci., Carbohydr. Polym., Nanoscale Adv., Colloids and Surfaces B, Langmuir, and Acta Phys-Chim. Sin.
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 Scoups and DOAJ.
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