title: New Peptide-Conjugated Chlorin-Type Photosensitizer Targeting Neuropilin-1 for Anti-Vascular Targeted Photodynamic Therapy.
abstract: Photodynamic therapy (PDT) is a cancer treatment modality that requires three components, namely light, dioxygen and a photosensitizing agent. After light excitation, the photosensitizer (PS) in its excited state transfers its energy to oxygen, which leads to photooxidation reactions. In order to improve the selectivity of the treatment, research has focused on the design of PS covalently attached to a tumor-targeting moiety. In this paper, we describe the synthesis and the physico-chemical and photophysical properties of six new peptide-conjugated photosensitizers designed for targeting the neuropilin-1 (NRP-1) receptor. We chose a TPC (5-(4-carboxyphenyl)-10,15, 20-triphenyl chlorine as photosensitizer, coupled via three different spacers (aminohexanoic acid, 1-amino-3,6-dioxaoctanoic acid, and 1-amino-9-aza-3,6,12,15-tetraoxa-10-on-heptadecanoic acid) to two different peptides (DKPPR and TKPRR). The affinity towards the NRP-1 receptor of the conjugated chlorins was evaluated along with in vitro and in vivo stability levels. The tissue concentration of the TPC-conjugates in animal model shows good distribution, especially for the DKPPR conjugates. The novel peptide-PS conjugates proposed in this study were proven to have potential to be further developed as future NRP-1 targeting photodynamic therapy agent.
authors.affiliation: LCPM UMR 7375, CNRS, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. bibwahab@gmail.com.|LCPM, UMR 7375, Université de Lorraine, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. bibwahab@gmail.com.|School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia. bibwahab@gmail.com.
authors.forename: Ezatul Ezleen
authors.initials: EE
authors.lastname: Kamarulzaman
authors.affiliation: LCPM UMR 7375, CNRS, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. bibwahab@gmail.com.|LCPM, UMR 7375, Université de Lorraine, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. bibwahab@gmail.com.|School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia. bibwahab@gmail.com.
authors.forename: Amirah Mohd
authors.initials: AM
authors.lastname: Gazzali
authors.affiliation: LCPM UMR 7375, CNRS, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. samir.acherar@univ-lorraine.fr.|LCPM, UMR 7375, Université de Lorraine, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. samir.acherar@univ-lorraine.fr.
authors.forename: Samir
authors.initials: S
authors.lastname: Acherar
authors.affiliation: LRGP, UMR 7274, CNRS, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. celine.frochot@univ-lorraine.fr.|LRGP, UMR 7274, Université de Lorraine, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. celine.frochot@univ-lorraine.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Frochot
authors.affiliation: CRAN, UMR 7039, Université de Lorraine, Campus Sciences, BP 70239-54506 Vandoeuvre Cedex, France.|CRAN, UMR 7039, CNRS, Campus Sciences, BP 70239-54506 Vandoeuvre Cedex, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Barberi-Heyob
authors.affiliation: CRAN, UMR 7039, Université de Lorraine, Campus Sciences, BP 70239-54506 Vandoeuvre Cedex, France. cedric.boura@univ-lorraine.fr.|CRAN, UMR 7039, CNRS, Campus Sciences, BP 70239-54506 Vandoeuvre Cedex, France. cedric.boura@univ-lorraine.fr.
authors.forename: Cédric
authors.initials: C
authors.lastname: Boura
authors.affiliation: SRSMC, UMR 7565 ICPM, Université de Lorraine, 1 boulevard Arago, 57078 Metz Cedex 3, France. patrick.chaimbault@univ-lorraine.fr.|SRSMC, UMR 7565 ICPM, CNRS, 1 boulevard Arago, 57078 Metz Cedex 3, France. patrick.chaimbault@univ-lorraine.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chaimbault
authors.affiliation: LCP-A2MC, EA 4632, ICPM, 1 boulevard Arago, 57078 Metz Cedex 3, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Sibille
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia. bibwahab@gmail.com.
authors.forename: Habibah A
authors.initials: HA
authors.lastname: Wahab
authors.affiliation: LCPM UMR 7375, CNRS, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. regis.vanderesse@univ-lorraine.fr.|LCPM, UMR 7375, Université de Lorraine, ENSIC, 1 rue Grandville, BP 20451-54001 Nancy Cedex, France. regis.vanderesse@univ-lorraine.fr.
authors.forename: Régis
authors.initials: R
authors.lastname: Vanderesse
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D039942:Neuropilin-1 / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011485:Protein Binding; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C513508:5-(4-carboxyphenyl)-10,15,20-triphenylchlorin; D010455:Peptides; D017319:Photosensitizing Agents; D011166:Porphyrins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D039942:Neuropilin-1; D011092:Polyethylene Glycols; D010100:Oxygen
keywords: in vivo stability; neuropilin-1; peptide targeted photosensitizer; photodynamic therapy