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

Authors Narsireddy A, Vijayashree K, Adimoolam MG, Manorama SV, Rao NM

Received 29 May 2015

Accepted for publication 13 August 2015

Published 3 November 2015 Volume 2015:10(1) Pages 6865—6878

DOI https://doi.org/10.2147/IJN.S89474

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Zhengjian Lv

Peer reviewer comments 5

Editor who approved publication: Dr Lei Yang

Amreddy Narsireddy,1 Kurra Vijayashree,2 Mahesh G Adimoolam,1 Sunkara V Manorama,1 Nalam M Rao2

1CSIR – Indian Institute of Chemical Technology, 2CSIR – Centre for Cellular and Molecular Biology, Hyderabad, India

Abstract: 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

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