Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy
Photodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.679128/full |
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| author | Letícia B. Silva Kelly A. D. F. Castro Caroline E. A. Botteon Cristiano L. P. Oliveira Roberto S. da Silva Priscyla D. Marcato |
| author_facet | Letícia B. Silva Kelly A. D. F. Castro Caroline E. A. Botteon Cristiano L. P. Oliveira Roberto S. da Silva Priscyla D. Marcato |
| author_sort | Letícia B. Silva |
| collection | DOAJ |
| description | Photodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells. In this context, porphyrins are interesting PS because they are robust, have high chemical, photo, thermal, and oxidative stability, and can generate singlet oxygen (1O2). However, porphyrins exhibit low solubility and a strong tendency to aggregate in a biological environment which limits their clinical application. To overcome these challenges, we developed hybrid nanostructures to immobilize 5,10,15,20-tetrakis[(4-carboxyphenyl) thio-2,3,5,6-tetrafluorophenyl] (P), a new third-generation PS. The biological effect of this system was evaluated against bladder cancer (BC) cells with or without light exposition. The nanostructure composed of lipid carriers coated by porphyrin-chitosan (P-HNP), presented a size of ca. 130 nm and low polydispersity (ca. 0.25). The presence of the porphyrin-chitosan (P-chitosan) on lipid nanoparticle surfaces increased the nanoparticle size, changed the zeta potential to positive, decreased the recrystallization index, and increased the thermal stability of nanoparticles. Furthermore, P-chitosan incorporation on nanoparticles increased the stability and enhanced the self-organization of the system and the formation of spherical structures, as observed by small-angle X-ray scattering (SAXS) analysis. Furthermore, the immobilization process maintained the P photoactivity and improved the photophysical properties of PS, minimizing its aggregation in the cell culture medium. In the photoinduction assays, the P-HNP displayed high phototoxicity with IC50 3.2-folds lower than free porphyrin. This higher cytotoxic effect can be correlated to the high cellular uptake of porphyrin immobilized, as observed by confocal images. Moreover, the coated nanoparticles showed mucoadhesive properties interesting to its application in vivo. Therefore, the physical and chemical properties of nanoparticles may be relevant to improve the porphyrin photodynamic activity in BC cells. |
| first_indexed | 2024-12-17T00:00:01Z |
| format | Article |
| id | doaj.art-b66b5993dfe249168172c6593d94a180 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-17T00:00:01Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-b66b5993dfe249168172c6593d94a1802022-12-21T22:11:06ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-09-01910.3389/fbioe.2021.679128679128Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic TherapyLetícia B. Silva0Kelly A. D. F. Castro1Caroline E. A. Botteon2Cristiano L. P. Oliveira3Roberto S. da Silva4Priscyla D. Marcato5Department of Pharmaceutical Science, GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Pharmaceutical Science, GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilInstitute of Physics, University of São Paulo, São Paulo, BrazilDepartment of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilDepartment of Pharmaceutical Science, GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, BrazilPhotodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells. In this context, porphyrins are interesting PS because they are robust, have high chemical, photo, thermal, and oxidative stability, and can generate singlet oxygen (1O2). However, porphyrins exhibit low solubility and a strong tendency to aggregate in a biological environment which limits their clinical application. To overcome these challenges, we developed hybrid nanostructures to immobilize 5,10,15,20-tetrakis[(4-carboxyphenyl) thio-2,3,5,6-tetrafluorophenyl] (P), a new third-generation PS. The biological effect of this system was evaluated against bladder cancer (BC) cells with or without light exposition. The nanostructure composed of lipid carriers coated by porphyrin-chitosan (P-HNP), presented a size of ca. 130 nm and low polydispersity (ca. 0.25). The presence of the porphyrin-chitosan (P-chitosan) on lipid nanoparticle surfaces increased the nanoparticle size, changed the zeta potential to positive, decreased the recrystallization index, and increased the thermal stability of nanoparticles. Furthermore, P-chitosan incorporation on nanoparticles increased the stability and enhanced the self-organization of the system and the formation of spherical structures, as observed by small-angle X-ray scattering (SAXS) analysis. Furthermore, the immobilization process maintained the P photoactivity and improved the photophysical properties of PS, minimizing its aggregation in the cell culture medium. In the photoinduction assays, the P-HNP displayed high phototoxicity with IC50 3.2-folds lower than free porphyrin. This higher cytotoxic effect can be correlated to the high cellular uptake of porphyrin immobilized, as observed by confocal images. Moreover, the coated nanoparticles showed mucoadhesive properties interesting to its application in vivo. Therefore, the physical and chemical properties of nanoparticles may be relevant to improve the porphyrin photodynamic activity in BC cells.https://www.frontiersin.org/articles/10.3389/fbioe.2021.679128/fullhybrid nanoparticleschitosanporphyrinPDT-photodynamic therapybladder cancer cells |
| spellingShingle | Letícia B. Silva Kelly A. D. F. Castro Caroline E. A. Botteon Cristiano L. P. Oliveira Roberto S. da Silva Priscyla D. Marcato Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy Frontiers in Bioengineering and Biotechnology hybrid nanoparticles chitosan porphyrin PDT-photodynamic therapy bladder cancer cells |
| title | Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy |
| title_full | Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy |
| title_fullStr | Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy |
| title_full_unstemmed | Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy |
| title_short | Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy |
| title_sort | hybrid nanoparticles as an efficient porphyrin delivery system for cancer cells to enhance photodynamic therapy |
| topic | hybrid nanoparticles chitosan porphyrin PDT-photodynamic therapy bladder cancer cells |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.679128/full |
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