Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy

Autor(es)

Silva, Leticia B. ^[1] ; Castro, Kelly A. D. F. ^[2] ; Botteon, Caroline E. A. ^[1] ; Oliveira, Cristiano L. P. ^[3] ; da Silva, Roberto S. ^[2] ; Marcato, Priscyla D. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, GNanoBio, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept BioMol Sci, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Inst Phys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY; v. 9, SEP 17 2021.
• Citações Web of Science: 0

Resumo

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 (O-1(2)). 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.</p> (AU)

• Processo FAPESP: 19/19448-8 - Efeito da fotobiomodulação como adendo sinergístico na foto-citotoxicidade de compostos rutênio-ftalocianinas como produtores de óxido nítrico e oxigênio singleto: avaliação bioquímica in vitro em linhagens tumorais bi- e tridimensional (3D)
• Beneficiário: Roberto Santana da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/13465-5 - Desenvolvimento de nanopartículas poliméricas contendo própolis vermelha brasileira e avaliação antitumoral in vitro e in vivo em cânceres urológicos
• Beneficiário: Priscyla Daniely Marcato Gaspari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/12707-0 - Citotoxicidade e foto-citotoxicidade de compostos rutênio-ftalocianinas como produtores de óxido nítrico e oxigênio singleto em linhagens de células cancerígenas. Proposta para uma nova classe de metalo-drogas
• Beneficiário: Roberto Santana da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular