Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery
Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/312 |
| _version_ | 1797358650339098624 |
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| author | Sara Gimondi Helena Ferreira Rui L. Reis Nuno M. Neves |
| author_facet | Sara Gimondi Helena Ferreira Rui L. Reis Nuno M. Neves |
| author_sort | Sara Gimondi |
| collection | DOAJ |
| description | Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPs’ uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect. |
| first_indexed | 2024-03-08T15:05:06Z |
| format | Article |
| id | doaj.art-31573dbe55f3453a9ad3f7429a760ec3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:06Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-31573dbe55f3453a9ad3f7429a760ec32024-01-10T14:58:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125131210.3390/ijms25010312Intracellular Trafficking of Size-Tuned Nanoparticles for Drug DeliverySara Gimondi0Helena Ferreira1Rui L. Reis2Nuno M. Neves33B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Guimarães, PortugalPolymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPs’ uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect.https://www.mdpi.com/1422-0067/25/1/312polymeric nanoparticlessize-controlled nanoparticlesPEGylationinternalizationintracellular trafficking |
| spellingShingle | Sara Gimondi Helena Ferreira Rui L. Reis Nuno M. Neves Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery International Journal of Molecular Sciences polymeric nanoparticles size-controlled nanoparticles PEGylation internalization intracellular trafficking |
| title | Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery |
| title_full | Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery |
| title_fullStr | Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery |
| title_full_unstemmed | Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery |
| title_short | Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery |
| title_sort | intracellular trafficking of size tuned nanoparticles for drug delivery |
| topic | polymeric nanoparticles size-controlled nanoparticles PEGylation internalization intracellular trafficking |
| url | https://www.mdpi.com/1422-0067/25/1/312 |
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