Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao21CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, IndiaAbstract: Challenges in photodynamic therapy (PDT) include developmen...

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Autores principales:	Narsireddy A, Vijayashree K, Adimoolam MG, Manorama SV, Rao NM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f3efce58317340ebae7f1a0a3945b41e
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spelling	oai:doaj.org-article:f3efce58317340ebae7f1a0a3945b41e2021-12-02T01:08:05ZPhotosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy1178-2013https://doaj.org/article/f3efce58317340ebae7f1a0a3945b41e2015-11-01T00:00:00Zhttps://www.dovepress.com/photosensitizer-and-peptide-conjugated-pamam-dendrimer-for-targeted-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao21CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, IndiaAbstract: Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.Keywords: photodynamic therapy, dendrimers, nanoparticle, targeted delivery, Affibody, xenograft animal modelNarsireddy AVijayashree KAdimoolam MGManorama SVRao NMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6865-6878 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Narsireddy A Vijayashree K Adimoolam MG Manorama SV Rao NM Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy
description	Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao21CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, IndiaAbstract: Challenges in photodynamic therapy (PDT) include development of efficient near infrared-sensitive photosensitizers (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine [PS]) and targeted delivery of PS to the tumor tissue. In this study, a dual functional dendrimer was synthesized for targeted PDT. For targeting, a poly(amidoamine) dendrimer (G4) was conjugated with a PS and a nitrilotriacetic acid (NTA) group. A peptide specific to human epidermal growth factor 2 was expressed in Escherichia coli with a His-tag and was specifically bound to the NTA group on the dendrimer. Reaction conditions were optimized to result in dendrimers with PS and the NTA at a fractional occupancy of 50% and 15%, respectively. The dendrimers were characterized by nuclear magnetic resonance, matrix-assisted laser desorption/ionization, absorbance, and fluorescence spectroscopy. Using PS fluorescence, cell uptake of these particles was confirmed by confocal microscopy and fluorescence-activated cell sorting. PS-dendrimers are more efficient than free PS in PDT-mediated cell death assays in HER2 positive cells, SK-OV-3. Similar effects were absent in HER2 negative cell line, MCF-7. Compared to free PS, the PS-dendrimers have shown significant tumor suppression in a xenograft animal tumor model. Conjugation of a PS with dendrimers and with a targeting agent has enhanced photodynamic therapeutic effects of the PS.Keywords: photodynamic therapy, dendrimers, nanoparticle, targeted delivery, Affibody, xenograft animal model
format	article
author	Narsireddy A Vijayashree K Adimoolam MG Manorama SV Rao NM
author_facet	Narsireddy A Vijayashree K Adimoolam MG Manorama SV Rao NM
author_sort	Narsireddy A
title	Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy
title_short	Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy
title_full	Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy
title_fullStr	Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy
title_full_unstemmed	Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy
title_sort	photosensitizer and peptide-conjugated pamam dendrimer for targeted in vivo photodynamic therapy
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/f3efce58317340ebae7f1a0a3945b41e
work_keys_str_mv	AT narsireddya photosensitizerandpeptideconjugatedpamamdendrimerfortargetedinvivophotodynamictherapy AT vijayashreek photosensitizerandpeptideconjugatedpamamdendrimerfortargetedinvivophotodynamictherapy AT adimoolammg photosensitizerandpeptideconjugatedpamamdendrimerfortargetedinvivophotodynamictherapy AT manoramasv photosensitizerandpeptideconjugatedpamamdendrimerfortargetedinvivophotodynamictherapy AT raonm photosensitizerandpeptideconjugatedpamamdendrimerfortargetedinvivophotodynamictherapy
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Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy

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