Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J-Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging

Abstract

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I 895 /I 780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibodyconjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.

In vivo quantitative characterization of nano adjuvant transport in the tracheal layer by photoacoustic imaging

“…Among them, BIA has two characteristic peaks at 730 nm and 810 nm respectively. The peak absorption of ICG is observed around 750-780 nm, whereas the absorption peaks of BIA are around 800-830 nm and show a significant redshift due to the aggregation of ICG [ 42 , 43 ]. In addition, the characteristic peaks of BIA did not shift at different concentrations, and the absorption value increased with increasing concentration, as shown in Fig.…”

Diagnosis and treatment status of inoperable locally advanced breast cancer and the application value of inorganic nanomaterials

“…INPs utilized as imaging elements in PAI significantly boost breast cancer's detection capabilities [ 82 ] and improve the dynamic observation and diagnosis precision of tumors by providing high-contrast signals.…”