c(RGDfK)- and ZnTriMPyP-Bound Polymeric Nanocarriers for Tumor-Targeted Photodynamic Therapy

Elena de las Heras; Ester Boix-Garriga; Francesca Bryden; Montserrat Agut; Margarita Mora; M. Lluïsa Sagristá; Ross W. Boyle; Norbert Lange; Santi Nonell

doi:10.1111/php.13238

c(RGDfK)- and ZnTriMPyP-Bound Polymeric Nanocarriers for Tumor-Targeted Photodynamic Therapy

Elena de las Heras, Ester Boix-Garriga, Francesca Bryden, Montserrat Agut, Margarita Mora, M. Lluïsa Sagristá, Ross W. Boyle, Norbert Lange, Santi Nonell

Producció científica: Article en revista indexada › Article › Avaluat per experts

Resum

Active targeting strategies are currently being extensively investigated in order to enhance the selectivity of photodynamic therapy. The aim of the present research was to evaluate whether the external decoration of nanopolymeric carriers with targeting peptides could add more value to a photosensitizer formulation and increase antitumor therapeutic efficacy and selectivity. To this end, we assessed PLGA-PLA-PEG nanoparticles (NPs) covalently attached to a hydrophilic photosensitizer 5-[4-azidophenyl]-10,15,20-tri-(N-methyl-4-pyridinium)porphyrinato zinc (II) trichloride (ZnTriMPyP) and also to c(RGDfK) peptides, in order to target α_vβ₃ integrin-expressing cells. In vitro phototoxicity investigations showed that the ZnTriMPyP-PLGA-PLA-PEG-c(RGDfK) nanosystem is effective at submicromolar concentrations, is devoid of dark toxicity, successfully targets α_vβ₃ integrin-expressing cells and is 10-fold more potent than related nanosystems where the PS is occluded instead of covalently bound.

Idioma original	Anglès
Pàgines (de-a)	570-580
Nombre de pàgines	11
Revista	Photochemistry and Photobiology
Volum	96
Número	3
DOIs	https://doi.org/10.1111/php.13238
Estat de la publicació	Publicada - 1 de maig 2020

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10.1111/php.13238

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title = "c(RGDfK)- and ZnTriMPyP-Bound Polymeric Nanocarriers for Tumor-Targeted Photodynamic Therapy",

abstract = "Active targeting strategies are currently being extensively investigated in order to enhance the selectivity of photodynamic therapy. The aim of the present research was to evaluate whether the external decoration of nanopolymeric carriers with targeting peptides could add more value to a photosensitizer formulation and increase antitumor therapeutic efficacy and selectivity. To this end, we assessed PLGA-PLA-PEG nanoparticles (NPs) covalently attached to a hydrophilic photosensitizer 5-[4-azidophenyl]-10,15,20-tri-(N-methyl-4-pyridinium)porphyrinato zinc (II) trichloride (ZnTriMPyP) and also to c(RGDfK) peptides, in order to target αvβ3 integrin-expressing cells. In vitro phototoxicity investigations showed that the ZnTriMPyP-PLGA-PLA-PEG-c(RGDfK) nanosystem is effective at submicromolar concentrations, is devoid of dark toxicity, successfully targets αvβ3 integrin-expressing cells and is 10-fold more potent than related nanosystems where the PS is occluded instead of covalently bound.",

author = "{de las Heras}, Elena and Ester Boix-Garriga and Francesca Bryden and Montserrat Agut and Margarita Mora and Sagrist{\'a}, {M. Llu{\"i}sa} and Boyle, {Ross W.} and Norbert Lange and Santi Nonell",

note = "Funding Information: This research was funded by Ministerio de Econom{\'i}a y Competitividad (grant numbers CTQ2013‐48767‐C3‐1‐R and CTQ2016‐78454‐C2‐1‐R). EBG thank predoctoral fellowship BES‐2011‐044125. Publisher Copyright: {\textcopyright} 2020 American Society for Photobiology",

year = "2020",

month = may,

day = "1",

doi = "10.1111/php.13238",

language = "English",

volume = "96",

pages = "570--580",

journal = "Photochemistry and Photobiology",

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AU - de las Heras, Elena

AU - Boix-Garriga, Ester

AU - Bryden, Francesca

AU - Agut, Montserrat

AU - Mora, Margarita

AU - Sagristá, M. Lluïsa

AU - Boyle, Ross W.

AU - Lange, Norbert

AU - Nonell, Santi

N1 - Funding Information: This research was funded by Ministerio de Economía y Competitividad (grant numbers CTQ2013‐48767‐C3‐1‐R and CTQ2016‐78454‐C2‐1‐R). EBG thank predoctoral fellowship BES‐2011‐044125. Publisher Copyright: © 2020 American Society for Photobiology

PY - 2020/5/1

Y1 - 2020/5/1

N2 - Active targeting strategies are currently being extensively investigated in order to enhance the selectivity of photodynamic therapy. The aim of the present research was to evaluate whether the external decoration of nanopolymeric carriers with targeting peptides could add more value to a photosensitizer formulation and increase antitumor therapeutic efficacy and selectivity. To this end, we assessed PLGA-PLA-PEG nanoparticles (NPs) covalently attached to a hydrophilic photosensitizer 5-[4-azidophenyl]-10,15,20-tri-(N-methyl-4-pyridinium)porphyrinato zinc (II) trichloride (ZnTriMPyP) and also to c(RGDfK) peptides, in order to target αvβ3 integrin-expressing cells. In vitro phototoxicity investigations showed that the ZnTriMPyP-PLGA-PLA-PEG-c(RGDfK) nanosystem is effective at submicromolar concentrations, is devoid of dark toxicity, successfully targets αvβ3 integrin-expressing cells and is 10-fold more potent than related nanosystems where the PS is occluded instead of covalently bound.

AB - Active targeting strategies are currently being extensively investigated in order to enhance the selectivity of photodynamic therapy. The aim of the present research was to evaluate whether the external decoration of nanopolymeric carriers with targeting peptides could add more value to a photosensitizer formulation and increase antitumor therapeutic efficacy and selectivity. To this end, we assessed PLGA-PLA-PEG nanoparticles (NPs) covalently attached to a hydrophilic photosensitizer 5-[4-azidophenyl]-10,15,20-tri-(N-methyl-4-pyridinium)porphyrinato zinc (II) trichloride (ZnTriMPyP) and also to c(RGDfK) peptides, in order to target αvβ3 integrin-expressing cells. In vitro phototoxicity investigations showed that the ZnTriMPyP-PLGA-PLA-PEG-c(RGDfK) nanosystem is effective at submicromolar concentrations, is devoid of dark toxicity, successfully targets αvβ3 integrin-expressing cells and is 10-fold more potent than related nanosystems where the PS is occluded instead of covalently bound.

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c(RGDfK)- and ZnTriMPyP-Bound Polymeric Nanocarriers for Tumor-Targeted Photodynamic Therapy

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