Porphyrin-Loaded TyroSpheres for the Intracellular Delivery of Drugs and Photoinduced Oxidant Species

Autor(es)

Tsubone, Tayana Mazin ^[1] ; Zhang, Zheng ^[2] ; Goyal, Ritu ^[2] ; Santacruz, Carolina ^[1] ; Martins, Waleska Kerllen ^[3] ; Kohn, Joachim ^[2] ; Baptista, Mauricio S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508900 Sao Paulo - Brazil

^[2] Rutgers State Univ, New Jersey Ctr Biomat, Piscataway, NJ 08854 - USA

^[3] Anhanguera Univ Sao Paulo, BR-05145200 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR PHARMACEUTICS; v. 17, n. 8, p. 2911-2924, AUG 3 2020.
• Citações Web of Science: 0

Resumo

In order to understand the intracellular delivery of drugs and to improve the cell killing efficiency of photosensitizers (PSs) used in photodynamic therapy (PDT), we prepared TyroSphere nanoparticles, which are triblock polymer {[}poly(ethylene glycol)-block-oligo(desaminotyrosyltyrosine octyl ester suberate)-block-poly(ethylene glycol)] aggregates, loaded with amphiphilic porphyrins with either positive (CisDiMPyP) or negative (TPPS2a) charges. Their physicochemical and photochemical properties were investigated, as well as the efficiency and mechanism of PDT death in a cervical cancer cell line (HeLa). The photophysical properties of both PSs were improved when loaded in the nanocarrier, with a decrease in aggregation as well as an increase in the yield of singlet oxygen generation. The physical and chemical stability of TyroSphere nanoparticles allows them to enter cells and to promote the slow intracellular delivery of part of the PSs. Confocal steady-state and lifetime-resolved fluorescence imaging microscopy data showed that the released PSs are free to target their natural intracellular targets, which are mitochondria and lysosomes for CisDiMPyP and TPPS2a, respectively. The photodynamic efficiency of cell killing was increased considerably compared with the free PSs (similar to 3x), but the mechanism of cell death was the same as that of the free PSs, which are acute necro-apoptosis for CisDiMPyP and autophagy malfunction for TPPS 2.1, reflecting the specific damage in mitochondria and lysosomes, respectively. We are confident that TyroSpheres provide a novel and efficient platform to administrate PDT photosensitizers, as well as other drugs with intracellular targets. (AU)

• Processo FAPESP: 13/16532-1 - Mecanismo da internalização fotoquímica
• Beneficiário: Tayana Mazin Tsubone
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs