title: Targeted in vivo photodynamic therapy with epidermal growth factor receptor-specific peptide linked nanoparticles.
abstract: In targeted photodynamic therapy (tPDT), photosensitizers (PS) are targeted to disease tissue to reduce the dosage of PS and in addition to reduce the photo damage to the non-target tissue. We synthesized iron oxide nanoparticles (NP) armored with tumor targeting peptide and PS for targeted PDT. Chitosan covered Fe3O4 NPs (30 nm) were deposited with gold NPs to generate two distinct chemical surfaces. To the gold particles PS was attached with a lipoic acid linker. Human epidermal growth factor receptor (hEGFR)-specific peptide was also attached to the same particles via a nickel-nitrilotriacetic acid linker attached to the chitosan. Using these nanoparticles, peptide specific uptake and PDT mediated cell death of the SK-OV-3 cells (Her2(+) positive cells) were demonstrated by confocal microscopy, T2 imaging and viability assays. Peptide mediated preferential distribution of these NPs into tumor tissue was also shown in a xenograft tumor model. After one intravenous injection and one PDT dose, peptide bound NPs retarded tumor growth significantly compared to dark controls or treatments with NPs without peptide. The tumor retardation by targeted NPs was achieved at a PS concentration of 3.9 nmol/animal, whereas similar effect was seen with free PS at 220 nmol/animal. Therapeutic potential of these peptide containing NPs would be a useful in targeted PDT and in imaging the target tissue.
authors.affiliation: CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
authors.forename: Amreddy
authors.initials: A
authors.lastname: Narsireddy
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
authors.forename: Kurra
authors.initials: K
authors.lastname: Vijayashree
authors.affiliation: Agricultural & Biological Engineering, Purdue University, 225 S. University Street West Lafayette, IN 47907-2093, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Irudayaraj
authors.affiliation: CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India. Electronic address: manorama@iict.res.in.
authors.forename: Sunkara V
authors.initials: SV
authors.lastname: Manorama
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India. Electronic address: madhu@ccmb.res.in.
authors.forename: Nalam M
authors.initials: NM
authors.lastname: Rao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D008024:Ligands; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008819:Mice, Nude; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011166:Porphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013499:Surface Properties; D008063:Thioctic Acid / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D048271:Chitosan; D004337:Drug Carriers; D006046:Gold; D008024:Ligands; D058185:Magnetite Nanoparticles; D009571:Nitrilotriacetic Acid; D009942:Organometallic Compounds; D010455:Peptides; D017319:Photosensitizing Agents; D011166:Porphyrins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D008063:Thioctic Acid; C088321:nickel nitrilotriacetic acid; C051232:5,10,15,20-tetra(4-hydroxyphenyl)porphyrin; C508053:ERBB2 protein, human
keywords: Affibody; Nanoparticle; Photodynamic therapy; Targeted delivery; Xenograft Animal model