{"title":"Facile One-Pot Preparation of Self-Assembled Hyaluronate/Doxorubicin Nanoaggregates for Cancer Therapy.","authors":"Yong Geun Lim, Hyung Geun Park, Kyeongsoon Park","doi":"10.3390/biomimetics10020091","DOIUrl":null,"url":null,"abstract":"<p><p>Hyaluronic acid (HA)-based delivery systems for doxorubicin (DOX) have been developed to selectively target cancer cells and enhance their therapeutic effects while reducing systemic side effects. However, conventional methods for preparing HA-based drug delivery systems are often limited by multistep synthetic processes, time-consuming purification, and the use of crosslinkers or surfactants, which can cause undesired toxicities. To resolve these issues, we developed a facile one-pot method to prepare self-assembled sodium hyaluronate/doxorubicin (HA/DOX) nanoaggregates by mixing HA and DOX. The self-assembled HA/DOX nanoaggregates were formed via cation-π interactions between the aromatic moiety of DOX and Na<sup>+</sup> ions in HA as well as electrostatic interactions between HA and DOX. The optimized HA/DOX nanoaggregates with a [DOX]/[HA] molar ratio of 5 had an average particle size of approximately 250 nm and a sphere-like shape. In vitro studies revealed that HA/DOX nanoaggregates effectively targeted CD44-overexpressing cancer cells, selectively delivering DOX into the cell nuclei more efficiently than free DOX and resulting in enhanced cytotoxic effects. Annexin V and transferase dUTP nick-end labeling assays confirmed that HA/DOX nanoaggregates induced apoptosis via DNA fragmentation more effectively than free DOX.</p>","PeriodicalId":8907,"journal":{"name":"Biomimetics","volume":"10 2","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853142/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomimetics","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3390/biomimetics10020091","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Hyaluronic acid (HA)-based delivery systems for doxorubicin (DOX) have been developed to selectively target cancer cells and enhance their therapeutic effects while reducing systemic side effects. However, conventional methods for preparing HA-based drug delivery systems are often limited by multistep synthetic processes, time-consuming purification, and the use of crosslinkers or surfactants, which can cause undesired toxicities. To resolve these issues, we developed a facile one-pot method to prepare self-assembled sodium hyaluronate/doxorubicin (HA/DOX) nanoaggregates by mixing HA and DOX. The self-assembled HA/DOX nanoaggregates were formed via cation-π interactions between the aromatic moiety of DOX and Na+ ions in HA as well as electrostatic interactions between HA and DOX. The optimized HA/DOX nanoaggregates with a [DOX]/[HA] molar ratio of 5 had an average particle size of approximately 250 nm and a sphere-like shape. In vitro studies revealed that HA/DOX nanoaggregates effectively targeted CD44-overexpressing cancer cells, selectively delivering DOX into the cell nuclei more efficiently than free DOX and resulting in enhanced cytotoxic effects. Annexin V and transferase dUTP nick-end labeling assays confirmed that HA/DOX nanoaggregates induced apoptosis via DNA fragmentation more effectively than free DOX.