Nanotech for enhanced diagnostic imaging and therapeutic applications

Liposomal J-aggregates of Indocyanine Green are nanoparticles designed for enhanced photoacoustic imaging and photothermal therapy. They offer improved photostability, longer circulation, and efficient heating, hence their promise for diagnostic and therapeutic applications.

Background

Photoacoustic imaging (PAI) is a promising non-invasive clinical imaging technique that combines the high contrast of optical absorption with the low attenuation of ultrasound waves. This method leverages the photoacoustic effect, where acoustic waves are generated following the absorption of electromagnetic energy, typically using non-ionizing pulsed lasers in the near-infrared (NIR) window.

Despite its potential, the clinical translation of PAI is hindered by the limitations of existing contrast agents. Commonly used agents, such as metallic and polymer-based nanoparticles, often suffer from poor photostability and questionable biocompatibility, which restricts their use in clinical settings.

Indocyanine Green (IcG), a small organic molecule, has been explored as a potential contrast agent due to its broad absorption profile and bio­compatibility. However, IcG’s rapid clearance from the body and its broad spectral profile limit its effectiveness for deep tissue imaging and accurate blood oxygen saturation (sO2) estimation.

Additionally, while IcG J‑aggregates (IcG‑JA) offer improved photostability and a redshifted absorption peak, their uncontrolled growth and size variability pose challenges for in vivo applications. Thus, there is a need for a more stable, biocompatible, and effective contrast agent that can overcome these limitations and enhance the diagnostic and therapeutic capabilities of PAI.

Technology description

This technology focuses on a method for synthesizing Liposomal J‑Aggregates of Indocyanine Green (L‑JA), which are nanoparticles designed for use in diagnostic and therapeutic applications, particularly in photoacoustic imaging and photothermal therapy. The process involves encapsulating Indocyanine Green (IcG) within liposomes using high-transition temperature lipids, which facilitates the formation of J-aggregates directly inside the liposomes at elevated temperatures. This method ensures uniform particle size and enhances the photostability and circulation time of the L‑JA particles.

The nanoparticles exhibit improved photoacoustic signal generation and superior photothermal heating efficiency at longer wavelengths, specifically with an 852nm laser. The encapsulation process is efficient, reducing synthesis time to about three days, and results in biocompatible and bio­degradable particles suitable for clinical applications.

The technology is differentiated by its ability to produce consistent and uniform L‑JA particles with enhanced properties over conventional monomeric IcG. The use of high-transition temperature lipids allows for the rapid formation of J‑aggregates within liposomes, significantly reducing synthesis time and improving batch-to-batch consistency. The redshifted absorption peak of the L‑JA particles allows for more effective imaging and therapy at greater depths, while their enhanced photostability makes them suitable for prolonged imaging sessions.

Additionally, the liposomal encapsulation extends the circulation time of the particles, providing significant contrast enhancement in photoacoustic images for up to 24 hours post-injection. This makes L‑JA a promising candidate for multimodal imaging and therapy, offering a safe, biodegradable, and effective alternative to metallic nanoparticles typically used in these applications.

Benefits

  • Enhanced photostability and longer circulation time compared to monomeric Indocyanine Green (IcG)
  • Improved photoacoustic signal generation and photothermal heating efficiency
  • Biocompatible, biodegradable, and suitable for clinical applications
  • Efficient synthesis process, reducing time to about three days
  • Uniform particle size and control over J-aggregate size
  • Potential for multimodal imaging and therapy applications
  • Effective at longer wavelengths, enhancing imaging depth and therapeutic potential
  • Safe and non-toxic at physiologically relevant concentrations
  • Potential for further modification for targeted therapeutic or diagnostic applications

Commercial applications

  • Photoacoustic imaging enhancement
  • Photothermal therapy efficiency
  • Biocompatible contrast agent
  • Longer circulation time

Patent link

https://onlinelibrary.wiley.com/doi/10.1002/adtp.202400042

 

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date
IRRADIATION AMENABLE LIPOSOMAL DYE AGGREGATES AND METHODS OF SYNTHESIS ANDUSE THEREOF Utility (Conversion) United States 18/665,948   5/16/2024