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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Tsubone, Tayana Mazin [1] ; Zhang, Zheng [2] ; Goyal, Ritu [2] ; Santacruz, Carolina [1] ; Martins, Waleska Kerllen [3] ; Kohn, Joachim [2] ; Baptista, Mauricio S. [1]
Total Authors: 7
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: MOLECULAR PHARMACEUTICS; v. 17, n. 8, p. 2911-2924, AUG 3 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 13/16532-1 - Mechanism of photochemical internalization
Grantee:Tayana Mazin Tsubone
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC