title: Photosensitizer and peptide-conjugated PAMAM dendrimer for targeted in vivo photodynamic therapy.
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.
authors.affiliation: CSIR - Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Amreddy
authors.initials: A
authors.lastname: Narsireddy
authors.affiliation: CSIR - Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Kurra
authors.initials: K
authors.lastname: Vijayashree
authors.affiliation: CSIR - Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Mahesh G
authors.initials: MG
authors.lastname: Adimoolam
authors.affiliation: CSIR - Indian Institute of Chemical Technology, Hyderabad, India.
authors.forename: Sunkara V
authors.initials: SV
authors.lastname: Manorama
authors.affiliation: CSIR - Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Nalam M
authors.initials: NM
authors.lastname: Rao
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D066244:Proton Magnetic Resonance Spectroscopy; D026082:Singlet Oxygen / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity
chemical_list: D001572:Benzofurans; D050091:Dendrimers; C104700:PAMAM Starburst; D010455:Peptides; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; C011238:1,3-diphenylisobenzofuran
keywords: Affibody; dendrimers; nanoparticle; photodynamic therapy; targeted delivery; xenograft animal model