title: Stable J-aggregation enabled dual photoacoustic and fluorescence nanoparticles for intraoperative cancer imaging.
abstract: J-aggregates display nanoscale optical properties which enable their use in fluorescence and photoacoustic imaging applications. However, control over their optical properties in an in vivo setting is hampered by the conformational lability of the J-aggregate structure in complex biological environments. J-aggregating nanoparticles (JNP) formed by self-assembly of bacteriopheophorbide-lipid (Bchl-lipid) in lipid nanovesicles represents a novel strategy to stabilize J-aggregates for in vivo bioimaging applications. We find that 15 mol% Bchl-lipid embedded within a saturated phospholipid bilayer vesicle was optimal in terms of maximizing Bchl-lipid dye loading, while maintaining a spherical nanoparticle morphology and retaining spectral properties characteristic of J-aggregates. The addition of cholesterol maintains the stability of the J-aggregate absorption band for up to 6 hours in the presence of 90% FBS. In a proof-of-concept experiment, we successfully applied JNPs as a fluorescence contrast agent for real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Lymph node metastasis delineation was further verified by visualizing the JNP within the excised lymph node using photoacoustic imaging. Using JNPs, we demonstrate the possibility of using J-aggregates as fluorescence and photoacoustic contrast agents and may potentially spur the development of other nanomaterials that can stably induce J-aggregation for in vivo cancer bioimaging applications.
authors.affiliation: Princess Margaret Cancer Centre and Techna Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Mojdeh
authors.initials: M
authors.lastname: Shakiba
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Ng
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Huynh
authors.forename: Harley
authors.initials: H
authors.lastname: Chan
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Charron
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Nidal
authors.initials: N
authors.lastname: Muhanna
authors.forename: F Stuart
authors.initials: FS
authors.lastname: Foster
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D005453:Fluorescence; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging*; D008051:Lipid Bilayers; D008198:Lymph Nodes / Q000000981:diagnostic imaging; D053758:Nanoparticles; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging*; D010743:Phospholipids; D061088:Photoacoustic Techniques; D011817:Rabbits
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids