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Descrição
The research of light’s interaction with a photoactive substance to promote cellular death was initially introduced by Oscar Raab in the late 1800s. (1) Since then, this technique – photodynamic therapy (PDT) – has been proposed to treat a wide range of maladies, from infectious illnesses to noncommunicable diseases, including cancer. Although it can be prescribed to treat precancerous lesions and some types of cancer, inefficient photosensitizer buildup at treatment site hampers PDT’s efficacy. Nanotechnology has been addressing drug delivery problems by the development of distinct nanostructured platforms capable of increasing pharmacological properties of molecules, such as solubility and circulating half-life. (2) The association of nanotechnology’s potential to enhance photosensitizer delivery to target tissues with PDT’s oxidative damage to induce cell death has been rising as prospect to optimize cancer treatment. In this study, we aim to verify and compare the efficiency of PDT using redox-responsive silica-based nanoparticles and membrane fusogenic liposomes (MFLs) carrying protoporphyrin IX (PpIX) in vitro, in both tumor and healthy cells.
Four polysilsesquioxane-PpIX nanoparticles were studied: silica and PpIX (Ctrl-PpIX-SiNps), the previous system containing a redox-responsive linker that can be broken under reducing environments usually found in cancer cells (RR-PpIX-SiNps), a RR-PpIX-SiNps functionalized with polyethylene glycol (PEG, PEG-RR-PpIX-SiNps) and PEG-RR-PpIX functionalized with folic acid (FA- PEG-RR-PpIX-SiNps). MFLs were synthetized with (MFL-PpIX) and without (MFL) the photosensitizer. Cytotoxicity was evaluated in healthy (human fibroblasts – HDFn cell line - and keratinocytes - HaCaT) and tumor cells (MCF-7 – human mammary carcinoma, B16-F10 – murine skin melanoma and A431 – human skin non-melanoma). Dose-response experiments revealed the higher susceptibility of B16-F10 cell line to PDT than HDFn cells: when incubated for 24 h with 50 µg/mL of nanoparticles, the viability of B16-F10 cells was reduced to approximately 20 %, while similar results were obtained in HDFn cultures when solutions over 150 µg/mL were used. The comparison of PDT effectiveness between nanostructured and free PpIX revealed that, when exposed to RR-PpIX-SiNPs, MCF-7 and A431 cells were more prone to PDT cytotoxic effects than the HaCaT cell line. Free PpIX, however, displayed high phototoxicity for MCF-7, A431 and HaCaT cells, inducing more than 90 % of cellular death in both cell lines. When melanoma cells (B16-F10) and fibroblasts (HDFn) are incubated for 24 hours with a final concentration of 1,5-15 µg/mL of MFL-PpIX, it was observed that B16-F10 internalize more PpIX than HDFn however both cell lines display the same viability reduction when irradiated with 50 J/cm² of 630 nm. The increased uptake of PpIX in tumor cells results in higher ROS production. When comparing the MFL-PpIX effect on cell viability to free PpIx, it was observed that, for both cell lines, the nanostructured photosensitizer presented lower cytotoxicity in the dark, but promoted the similar damage to the cells when PDT was performed with 50 J/cm² Further assays will evaluate mitochondrial membrane potential, apoptosis and necrosis rates, and the MFL-mediated PDT in non-melanoma skin cancer.
Referências
1 ABDEL-KADER, M. H. The journey of PDT throughout history: PDT from Pharos to present. In: KOSTRON, H.; HASAN, T. (ed.). Photodynamic medicine: from bench to clinic. Cambridge, UK: Royal Society of Chemistry, 2016. cap. 1. p. 1-21. (Comprehensive Series in Photochemical and Photobiological Sciences)
2 SHI, J. et al. Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Letters, v. 10, n. 9, p. 3223-3230, 2010.
| Subárea | Óptica e Lasers |
|---|---|
| Apresentação do trabalho acadêmico para o público geral | Não |
