title: Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer.
abstract: Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications.
authors.affiliation: Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), Singapore.
authors.forename: Ghayathri
authors.initials: G
authors.lastname: Balasundaram
authors.affiliation: Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), Singapore.
authors.forename: Chris Jun Hui
authors.initials: CJ
authors.lastname: Ho
authors.affiliation: Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (ASTAR), Singapore.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: Wouter
authors.initials: W
authors.lastname: Driessen
authors.affiliation: Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), Singapore.
authors.forename: U S
authors.initials: US
authors.lastname: Dinish
authors.affiliation: Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), Singapore.
authors.forename: Chi Lok
authors.initials: CL
authors.lastname: Wong
authors.affiliation: Institute of Biological and Medical Imaging, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (ASTAR), Singapore.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Bio-Optical Imaging Group, Singapore Bioimaging Consortium (SBIC), Singapore ; School of Physics, National University of Ireland, Galway, Ireland.
authors.forename: Malini
authors.initials: M
authors.lastname: Olivo
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D061088:Photoacoustic Techniques / Q000379:methods*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D003287:Contrast Media; D011108:Polymers; D005492:Folic Acid
keywords: breast cancer; conjugated polymers; molecular imaging; photoacoustic tomography