Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery
Self-assembling amphiphilic polymers represent highly promising materials with emerging applications across various fields. In these polymers, the presence of hydrophilic and hydrophobic segments within their structure drives the self-assembly process in aqueous environments, leading to organized st...
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/1420-3049/30/6/1349 |
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| author | Beatrice Zurletti Ilaria Andreana Iris Chiara Salaroglio Valeria Bincoletto Maela Manzoli Barbara Rolando Paola Milla Chiara Riganti Barbara Stella Silvia Arpicco |
| author_facet | Beatrice Zurletti Ilaria Andreana Iris Chiara Salaroglio Valeria Bincoletto Maela Manzoli Barbara Rolando Paola Milla Chiara Riganti Barbara Stella Silvia Arpicco |
| author_sort | Beatrice Zurletti |
| collection | DOAJ |
| description | Self-assembling amphiphilic polymers represent highly promising materials with emerging applications across various fields. In these polymers, the presence of hydrophilic and hydrophobic segments within their structure drives the self-assembly process in aqueous environments, leading to organized structures capable of incorporating lipophilic drugs. Their high chemical versatility enables the design of tailored structures to meet specific requirements, such as the active targeting ability, thereby broadening their potential applications. In this work, a polyethylene glycol-phospholipid conjugate was employed to form nanocarriers loaded with a lipophilic derivative of gemcitabine. To achieve nano-assemblies actively targeted towards cancer cells overexpressing the hyaluronic acid (HA) receptor CD44, a HA-phospholipid conjugate was co-formulated in various molar ratios (1%, 10%, and 20%). All formulations exhibited a mean diameter below 130 nm, a negative zeta potential (approximately −30 mV), and a high encapsulation efficiency (above 90%). These nano-assemblies demonstrated stability during storage and effectively released the encapsulated drug in a cell culture medium. Upon incubation with cancer cells, the nano-assemblies were internalized via a CD44 endocytosis-mediated mechanism, with the extent of internalization depending on the HA conjugate content. Consistently, cell viability studies revealed that the nanocarriers decorated with higher amounts of HA exerted a higher cytotoxicity, enabling a fine tuning of the nano-assembly properties. |
| format | Article |
| id | doaj-art-2b92ae32ca944c618a8e896512b44769 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-2b92ae32ca944c618a8e896512b447692025-08-20T01:49:05ZengMDPI AGMolecules1420-30492025-03-01306134910.3390/molecules30061349Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug DeliveryBeatrice Zurletti0Ilaria Andreana1Iris Chiara Salaroglio2Valeria Bincoletto3Maela Manzoli4Barbara Rolando5Paola Milla6Chiara Riganti7Barbara Stella8Silvia Arpicco9Department of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Oncology, Interdepartmental Center of Molecular Biotechnology “Guido Tarone”, University of Turin, Via Nizza 44, 10126 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Oncology, Interdepartmental Center of Molecular Biotechnology “Guido Tarone”, University of Turin, Via Nizza 44, 10126 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Turin, ItalySelf-assembling amphiphilic polymers represent highly promising materials with emerging applications across various fields. In these polymers, the presence of hydrophilic and hydrophobic segments within their structure drives the self-assembly process in aqueous environments, leading to organized structures capable of incorporating lipophilic drugs. Their high chemical versatility enables the design of tailored structures to meet specific requirements, such as the active targeting ability, thereby broadening their potential applications. In this work, a polyethylene glycol-phospholipid conjugate was employed to form nanocarriers loaded with a lipophilic derivative of gemcitabine. To achieve nano-assemblies actively targeted towards cancer cells overexpressing the hyaluronic acid (HA) receptor CD44, a HA-phospholipid conjugate was co-formulated in various molar ratios (1%, 10%, and 20%). All formulations exhibited a mean diameter below 130 nm, a negative zeta potential (approximately −30 mV), and a high encapsulation efficiency (above 90%). These nano-assemblies demonstrated stability during storage and effectively released the encapsulated drug in a cell culture medium. Upon incubation with cancer cells, the nano-assemblies were internalized via a CD44 endocytosis-mediated mechanism, with the extent of internalization depending on the HA conjugate content. Consistently, cell viability studies revealed that the nanocarriers decorated with higher amounts of HA exerted a higher cytotoxicity, enabling a fine tuning of the nano-assembly properties.https://www.mdpi.com/1420-3049/30/6/1349hyaluronic acid conjugatenano-assembliesCD44 receptortargeted drug delivery |
| spellingShingle | Beatrice Zurletti Ilaria Andreana Iris Chiara Salaroglio Valeria Bincoletto Maela Manzoli Barbara Rolando Paola Milla Chiara Riganti Barbara Stella Silvia Arpicco Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery Molecules hyaluronic acid conjugate nano-assemblies CD44 receptor targeted drug delivery |
| title | Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery |
| title_full | Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery |
| title_fullStr | Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery |
| title_full_unstemmed | Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery |
| title_short | Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery |
| title_sort | tailoring the composition of ha peg mixed nano assemblies for anticancer drug delivery |
| topic | hyaluronic acid conjugate nano-assemblies CD44 receptor targeted drug delivery |
| url | https://www.mdpi.com/1420-3049/30/6/1349 |
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