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.

Fluorescent J-aggregates of cyanine dyes: basic research and applications review

“…In this way, by modification of nanoparticles surface, their targeted accumulation in cancer tissues can be achieved [277]. The J-aggregates forming bacteriopheophorbidelipid dye complexes were embedded within the membrane of saturated phospholipid nanovesicles and this allowed their use as fluorescent nanoparticles for intraoperative imaging of potentially metastatic drainage lymph nodes near primary buccal tumors in a rabbit model of head and neck cancers [177]. More efforts are needed for making the nanoscale emitters with incorporation of different cyanine dyes that can absorb and emit light of different colors.…”

“…J-aggregates can be formed on lipid vesicle surface even if they do not possess long alkyl chains [176]. Such vesicles are prospective for bioimaging applications [177].…”

Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications

“…Compared to dye monomer, J -aggregate shows red-shifted absorption wavelength and higher absorption coefficient 143. Therefore, the use of a self-assembly nanostructure is another strategy to amplify the PA signals of organic dyes 144-146. For example, Chen et al reported an in situ tumor-specific supramolecular self-assembly (ICG doped nanofiber) for enhanced PAI 147.…”

Stable J‐Aggregation of an aza‐BODIPY‐Lipid in a Liposome for Optical Cancer Imaging

“…[1,2] However,e fforts to transform the liposome from asingular drug delivery vehicle into am ultimodal theranostics nanoplatform have centered around an "all-in-one" approach, wherein different functional moieties are combined for multifunctional utility.T his inherent complexity led to significant challenges in their clinical translation. [4] Previously developed porphyrin and porphyrin analog-based lipids such as bacteriochlorophylllipid [5,6] and texaphyrin-lipid [7,8] have shown unique stimuliresponsive properties and versatile metal-chelation capabilities,r espectively,f or cancer imaging.W ee nvision that it is possible for an on-porphyrin-based dye-lipid building block, such as aza-BODIPY,t oassemble into aliposomal structure that introduces novel nanoscale optical properties and broadens the purview of "one-for-all" lipid nanoparticles. [4] Previously developed porphyrin and porphyrin analog-based lipids such as bacteriochlorophylllipid [5,6] and texaphyrin-lipid [7,8] have shown unique stimuliresponsive properties and versatile metal-chelation capabilities,r espectively,f or cancer imaging.W ee nvision that it is possible for an on-porphyrin-based dye-lipid building block, such as aza-BODIPY,t oassemble into aliposomal structure that introduces novel nanoscale optical properties and broadens the purview of "one-for-all" lipid nanoparticles.…”