title: Indocyanine green-containing nanostructure as near infrared dual-functional targeting probes for optical imaging and photothermal therapy.
abstract: Indocyanine green (ICG) is a near-infrared (NIR) imaging agent and is also an ideal light absorber for laser-mediated photothermal therapy. This NIR dye could serve as a basis of a dual-functional probe with integrated optical imaging and photothermal therapy capabilities. However, applications of ICG remain limited by its concentration-dependent aggregation, poor aqueous stability, nonspecific binding to proteins and lack of target specificity. To overcome these limitations, a novel ICG-containing nanostructure is designed utilizing the noncovalent self-assembly chemistry between phospholipid-polyethylene glycol (PL-PEG) and ICG. The interactions between both amphiphilic ICG and PL-PEG were studied using absorption and fluorescence spectroscopy. The properties of ICG-PL-PEG nanoprobe, such as absorption and fluorescence spectra, stability, morphology and size distribution, were also investigated. Two representative targeting molecules, namely, a small molecule, folic acid (FA), and a large protein, integrin α(v)β₃ monoclonal antibody (mAb), were conjugated to the surface of ICG-PL-PEG nanoprobe, displaying the diversity of ligand conjugation. The target specificity was confirmed using three cell lines with different levels of available folate receptors (FRs) or integrin α(v)β₃ expression via laser scanning confocal microscope and flow cytometry. This targeting ICG-PL-PEG nanoprobe could be internalized into targeted cells via ligand-receptor mediated endocytosis pathway. Our in vitro experiments showed that internalized ICG-PL-PEG could be used for cell imaging and selective photothermal cell destruction. These results represent the first demonstration of the dual functionality of ICG-containing nanostructure for targeted optical imaging and photothermal therapy of cancerous cells. This novel ICG-PL-PEG nanostructure, when conjugated with other therapeutic and imaging agents, could become a multifunctional probe for cancer diagnosis and treatment.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng
authors.forename: Da
authors.initials: D
authors.lastname: Xing
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wu
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004396:Coloring Agents; D003952:Diagnostic Imaging; D005456:Fluorescent Dyes; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007208:Indocyanine Green; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000378:metabolism; D053685:Laser Therapy; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D010778:Photochemotherapy; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared
chemical_list: D000911:Antibodies, Monoclonal; D004396:Coloring Agents; D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D010743:Phospholipids; D011092:Polyethylene Glycols; D005492:Folic Acid; D007208:Indocyanine Green