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

Research output: Indexed journal article › Article › peer-review

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 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.

Original language	English
Pages (from-to)	570-580
Number of pages	11
Journal	Photochemistry and Photobiology
Volume	96
Issue number	3
DOIs	https://doi.org/10.1111/php.13238
Publication status	Published - 1 May 2020

Keywords

Plga-peg nanoparticles
Cyclic rgd
In-vitro
Alpha(v)beta(3) integrin
Prodrug nanoparticles
Peptide
Paclitaxel
Glioblastoma
Micelles
Delivery

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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.",

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AU - Mora, Margarita

AU - Sagristá, M. Lluïsa

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AU - Lange, Norbert

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

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