Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells
<b>Background:</b> Thyroid cancer (TC) is the most prevalent endocrine malignancy, and is categorized into well-differentiated and aggressive anaplastic types. Novel therapeutic modalities are needed for TC. Nanomedicine is a promising strategy for the development of precision medicine....
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2025-02-01
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| Online Access: | https://www.mdpi.com/1999-4923/17/2/263 |
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| author | Enrico Gallo Giovanni Smaldone Luca Cimmino Mariantonia Braile Francesca Maria Orlandella Neila Luciano Antonella Accardo Giuliana Salvatore |
| author_facet | Enrico Gallo Giovanni Smaldone Luca Cimmino Mariantonia Braile Francesca Maria Orlandella Neila Luciano Antonella Accardo Giuliana Salvatore |
| author_sort | Enrico Gallo |
| collection | DOAJ |
| description | <b>Background:</b> Thyroid cancer (TC) is the most prevalent endocrine malignancy, and is categorized into well-differentiated and aggressive anaplastic types. Novel therapeutic modalities are needed for TC. Nanomedicine is a promising strategy for the development of precision medicine. In this context, we investigated the use of nanogels (NGs) to deliver agents with different physicochemical properties, specifically the hydrophilic agent doxorubicin (DOX) and the hydrophobic compound curcumin (CUR), in TC cell lines. <b>Methods:</b> Nα-9-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) peptide-based NGs loaded with DOX and CUR were formulated using the solvent-switch method. DOX-loaded NGs were previously characterized. CUR-loaded NGs were characterized through rheology, scanning electron microscopy (SEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and Fourier transform infrared (FT-IR) spectroscopy. Confocal microscopy, q-RT-PCR, and ATP lite assays were performed to evaluate the uptake and delivery of DOX- and CUR-loaded NGs on TC cell lines. <b>Results:</b> CUR-loaded NGs exhibited a mean diameter of approximately 204.3 nm and a zeta potential of −34.6 mV, indicative of a good stability. In vitro release studies revealed a sustained release profile of CUR over 72 h. Functional analyses demonstrated that Fmoc-FF-loaded NGs were internalized into TC cell lines. They were primarily localized in the cytoplasm rather than in early endosomes, thereby ensuring intracellular stability. Furthermore, Fmoc-FF NGs reduced the nuclear uptake kinetics of DOX in TC cells, suggesting a potential reduction in dose-limiting toxicity. Comparative studies with CUR-loaded NGs revealed similar internalization and delayed nuclear uptake, highlighting the efficacy of Fmoc-FF NGs in delivering hydrophobic agents. <b>Conclusions:</b> Overall, the data suggest that Fmoc-FF NGs represent a promising strategy for delivering agents with diverse physicochemical properties in TC, enhancing their efficacy and safety and warranting further investigation. |
| format | Article |
| id | doaj-art-d83cf2ed30cc40f49b5a9797452f7582 |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Pharmaceutics |
| spelling | doaj-art-d83cf2ed30cc40f49b5a9797452f75822025-08-20T03:12:19ZengMDPI AGPharmaceutics1999-49232025-02-0117226310.3390/pharmaceutics17020263Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer CellsEnrico Gallo0Giovanni Smaldone1Luca Cimmino2Mariantonia Braile3Francesca Maria Orlandella4Neila Luciano5Antonella Accardo6Giuliana Salvatore7IRCCS SYNLAB SDN, 80146 Naples, ItalyIRCCS SYNLAB SDN, 80146 Naples, ItalyIRCCS SYNLAB SDN, 80146 Naples, ItalyIRCCS SYNLAB SDN, 80146 Naples, ItalyDipartimento delle Scienze Mediche, Motorie e del Benessere, Università degli Studi di Napoli “Parthenope”, 80133 Naples, ItalyDipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli “Federico II”, 80131 Naples, ItalyDipartimento di Farmacia, Università degli Studi di Napoli “Federico II”, 80131 Naples, ItalyDipartimento delle Scienze Mediche, Motorie e del Benessere, Università degli Studi di Napoli “Parthenope”, 80133 Naples, Italy<b>Background:</b> Thyroid cancer (TC) is the most prevalent endocrine malignancy, and is categorized into well-differentiated and aggressive anaplastic types. Novel therapeutic modalities are needed for TC. Nanomedicine is a promising strategy for the development of precision medicine. In this context, we investigated the use of nanogels (NGs) to deliver agents with different physicochemical properties, specifically the hydrophilic agent doxorubicin (DOX) and the hydrophobic compound curcumin (CUR), in TC cell lines. <b>Methods:</b> Nα-9-fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) peptide-based NGs loaded with DOX and CUR were formulated using the solvent-switch method. DOX-loaded NGs were previously characterized. CUR-loaded NGs were characterized through rheology, scanning electron microscopy (SEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and Fourier transform infrared (FT-IR) spectroscopy. Confocal microscopy, q-RT-PCR, and ATP lite assays were performed to evaluate the uptake and delivery of DOX- and CUR-loaded NGs on TC cell lines. <b>Results:</b> CUR-loaded NGs exhibited a mean diameter of approximately 204.3 nm and a zeta potential of −34.6 mV, indicative of a good stability. In vitro release studies revealed a sustained release profile of CUR over 72 h. Functional analyses demonstrated that Fmoc-FF-loaded NGs were internalized into TC cell lines. They were primarily localized in the cytoplasm rather than in early endosomes, thereby ensuring intracellular stability. Furthermore, Fmoc-FF NGs reduced the nuclear uptake kinetics of DOX in TC cells, suggesting a potential reduction in dose-limiting toxicity. Comparative studies with CUR-loaded NGs revealed similar internalization and delayed nuclear uptake, highlighting the efficacy of Fmoc-FF NGs in delivering hydrophobic agents. <b>Conclusions:</b> Overall, the data suggest that Fmoc-FF NGs represent a promising strategy for delivering agents with diverse physicochemical properties in TC, enhancing their efficacy and safety and warranting further investigation.https://www.mdpi.com/1999-4923/17/2/263thyroid cancernanogeldoxorubicincurcuminnanodelivery |
| spellingShingle | Enrico Gallo Giovanni Smaldone Luca Cimmino Mariantonia Braile Francesca Maria Orlandella Neila Luciano Antonella Accardo Giuliana Salvatore Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells Pharmaceutics thyroid cancer nanogel doxorubicin curcumin nanodelivery |
| title | Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells |
| title_full | Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells |
| title_fullStr | Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells |
| title_full_unstemmed | Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells |
| title_short | Fmoc-FF Nanogel-Mediated Delivery of Doxorubicin and Curcumin in Thyroid Cancer Cells |
| title_sort | fmoc ff nanogel mediated delivery of doxorubicin and curcumin in thyroid cancer cells |
| topic | thyroid cancer nanogel doxorubicin curcumin nanodelivery |
| url | https://www.mdpi.com/1999-4923/17/2/263 |
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