# Liposomal J-Aggregates of Indocyanine Green as a Multifunctional Contrast Agent for Photoacoustic Imaging and Photothermal Therapy

**Authors:** Noah Stern, Binita Shrestha, Susan Burrell, James Tunnell, Tyrone Porter

PMC · DOI: 10.7150/ntno.123184 · 2026-02-11

## TL;DR

This paper introduces liposomal J-aggregates of indocyanine green as a better contrast agent for imaging and therapy, offering improved performance over traditional ICG.

## Contribution

The novel contribution is the development of liposomal J-aggregates of ICG with enhanced optical and therapeutic properties.

## Key findings

- LJA exhibits redshifted peak absorbance and higher photostability compared to ICG.
- LJA shows improved tumor uptake and higher photothermal temperatures in vivo.
- LJA reduces tumor growth more effectively than ICG in photothermal therapy.

## Abstract

One of the major barriers to further clinical adoption of photoacoustic imaging (PAI) and photothermal therapy (PTT) is a lack of versatile and multi-faceted contrast agents. While indocyanine green (IcG) has gained considerable attention as a promising contrast agent, it is severely limited by rapid clearance time, low photostability, and a peak absorbance wavelength that coincides with hemoglobin. Herein, Liposomal J-aggregates of Indocyanine green (LJA) are presented as a superior alternative to generic IcG. They are a facilely produced, biodegradable nanoparticle offering advantageous physiochemical properties. J-aggregation results in a redshifted peak absorbance of increased magnitude and higher photostability compared to IcG. Liposome encapsulation increases circulation time leading to improved tumor uptake. Monte Carlo modeling of light interaction with tissue suggests that these improved optical properties make LJA a better contrast agent for PTT not only at longer wavelengths like 852nm and 890nm, but also at the commonly available and widely used 808nm. In vitro and in vivo testing support first approximations from modelling as LJA provide significantly higher photoacoustic signal, show increased tumor uptake, reach significantly higher temperatures under photothermal irradiation, and have the capacity to reduce tumor growth following therapy.

## Linked entities

- **Chemicals:** indocyanine green (PubChem CID 5282412), IcG (PubChem CID 5282412), LJA (PubChem CID 828139)

## Full-text entities

- **Diseases:** necrosis (MESH:D009336), Liposome (MESH:D015223), Toxicity (MESH:D064420), KPC (MESH:C565455), deoxygenated hemoglobin (MESH:D006445), burns (MESH:D002056), oxygenated (MESH:D000860), IcG (OMIM:614156), Tumor (MESH:D009369)
- **Chemicals:** argon (MESH:D001128), glucose (MESH:D005947), sO2 (MESH:D013458), APS (MESH:C031276), J (MESH:C000608249), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (MESH:C519184), PBS (MESH:D007854), melanin (MESH:D008543), Chloroform (MESH:D002725), Lipids (MESH:D008055), CO2 (MESH:D002245), TiO2 (MESH:C009495), N,N,N',N'-Tetramethylethylenediamine (MESH:C005798), polystyrene (MESH:D011137), PC (MESH:C053518), ICG (MESH:D007208), penicillin (MESH:D010406), bisacrylamide (MESH:C021221), DOTAP (MESH:C070046), CEM43 (-), porphyrin (MESH:D011166), acrylamide (MESH:D020106), Ethanol (MESH:D000431), cholesterol (MESH:D002784), polyethylene (MESH:D020959), India ink (MESH:C028433), phthalocyanine (MESH:C013647), isoflurane (MESH:D007530), DCP (MESH:C580746), methylene blue (MESH:D008751), copper sulfide (MESH:C017846), CCK-8 (MESH:D012844), Water (MESH:D014867), streptomycin (MESH:D013307), polyacrylamide (MESH:C016679), oxygen (MESH:D010100), gold (MESH:D006046), PA (MESH:D011478), Calcein AM (MESH:C085925)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** CEM43 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0219), KPC — Mus musculus (Mouse), Mouse pancreatic neoplasm, Cancer cell line (CVCL_A9ZK), IcG — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_DF41), mT4-2D — Homo sapiens (Human), Mitochondrial diabetes, Induced pluripotent stem cell (CVCL_A4RX)

## Figures

14 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12923309/full.md

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Source: https://tomesphere.com/paper/PMC12923309