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Photosensitizer and Peptide-Conjugated PAMAM Dendrimer for Targeted in Vivo Photodynamic Therapy

Photosensitizer and Peptide-Conjugated PAMAM Dendrimer for Targeted in Vivo Photodynamic Therapy

Amreddy Narsireddy, Kurra Vijayashree, Mahesh G Adimoolam, Sunkara V Manorama, Nalam M Rao

Int J Nanomedicine. 2015 Nov 3;10:6865-78.

PMID: 26604753

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP51094178	5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine		51094-17-8	Price

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