Tumor accumulation in polyethylene glycol-modified dendrimers with enhanced hydration
Hydration of materials affects their antifouling properties, and polyethylene glycol (PEG) is highly hydrated and biocompatible. PEGylated dendrimers have been studied as drug carriers that passively accumulate in tumors owing to their enhanced permeability and retention effect. In this study, we synthesized various PEGylated dendrimers with different PEG molecular weights, bound numbers, and dendrimer generations, and analyzed their hydration properties using differential scanning calorimetry and Fourier transform infrared spectroscopy. Intermediate water is defined as water molecules loosely bound to a material, the amount of which has been reported to be a useful index of bioinert properties. The amount of intermediate water was estimated from enthalpy change in melting peaks below 0 °C, considering a PEG-water eutectic system. Our results indicate that intermediate water was richer in PEGylated dendrimers with longer and more PEG chains. These PEGylated dendrimers, with longer and more PEG chains, also showed enhanced tumor accumulation after intravenous injection. The tumor-to-liver ratio correlated with the intermediate water content in the PEGylated dendrimers. This suggests that hydration is an important factor influencing dendrimer biodistribution, which is a possible criterion in designing nanocarriers for drug delivery systems. Researchers are exploring ways to improve drug delivery systems (DDS) to make cancer treatments more effective and reduce side effects. This study investigates how the structure of these nanoparticles affects their ability to deliver to tumor tissues. Researchers focused on PEGylated dendrimers, which are nanoparticles coated with polyethylene glycol (PEG). They created different versions of these dendrimers by varying the length and number of PEG chains. They then studied how these changes affected the nanoparticles’ hydration and distribution in the body. Using techniques like differential scanning calorimetry (DSC) and infrared spectroscopy, they measured how much water the dendrimers could hold. They found that longer PEG chains and higher PEG densities increased the intermediate water moderately interacted with materials, which improved the nanoparticles’ ability to reach tumors. The study concludes that hydration is an important factor in biodistribution, which is a possible criterion in designing nanocarriers. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author. In this study, polyethylene glycol (PEG)-modified dendrimers with different PEG molecular weights and PEG bound ratios were synthesized. Because the amount of intermediate water, which moderately interacts with materials, is known to be related to biocompatibility, we investigated the hydration and biodistribution of PEG-modified dendrimers with different structures. Dendrimers modified with longer and denser PEG chains had higher intermediate water content (WIM) and showed an increased tumor/liver ratio after the intravenous injection. These findings highlight hydration as a key physicochemical factor governing biodistribution, which is useful for optimizing nanocarriers in drug delivery systems.
Authors
- Junjie Yao (ORCID: https://orcid.org/0000-0002-2381-706X)
- Ayako Tsujimoto
- Akikazu Matsumoto (ORCID: https://orcid.org/0000-0002-4363-1393)
- Hao He (ORCID: https://orcid.org/0000-0001-9673-1331)
- Yuka Ikemoto (ORCID: https://orcid.org/0000-0001-6266-0977)
- Akiko Kubo (ORCID: https://orcid.org/0000-0002-6003-227X)
- Chie Kojima (ORCID: https://orcid.org/0000-0002-2208-5784)
Institutions
- Tokyo Institute of Technology (JP)
- Japan Synchrotron Radiation Research Institute (JP)
- Osaka Metropolitan University (JP)
Publication Details
- Journal
- NPG Asia Materials
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1038/s41427-025-00628-1
- Primary Topic
- Dendrimers and Hyperbranched Polymers
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Japan Society for the Promotion of Science