Advanced PAI contrast agents for early cancer detection

This technology involves creating biodegradable nanoparticles (nanocapsules) that selectively target diseased cells, such as cancer cells, for imaging and treatment. These nanocapsules contain indocyanine green (ICG) dye aggregates, which are stable and offer high contrast when using near-infrared photoacoustic imaging, enabling the detection of few cancer cells.

Background

Early detection via medical imaging remains a critical factor in surviving various diseases like cancer. Photoacoustic imaging (PAI) is a promising technique for molecular and functional tissue imaging. It uses the photoacoustic effect where pulsed laser irradiation generates acoustic waves in optically absorbing tissues. Endogenous biomolecules like hemoglobin and melanin can serve as contrast agents, but the need for exogenous agents is critical to enhance imaging capabilities. Current exogenous agents, particularly inorganic nanoparticles, face significant limitations due to their non-degradability and potential long-term toxicity, hindering their clinical translation.

Organic nanoparticles, such as those based on indocyanine green (ICG), offer a safer alternative. However, ICG monomers suffer from rapid clearance and poor stability in biological environments, limiting their efficacy. Its aggregates, ICG J-aggregates, with their sharp near-infrared (NIR) absorption peak and improved photostability, present a potential solution but are prone to dissociation in serum. And so, strategies for encapsulation, stabilizing these aggregates within a biocompatible and biodegradable matrix, can enhance their stability and imaging performance.

Technology description

UT Austin researchers have devised special nanoparticles (nanocapsules) to encapsulate (ICG) J-aggregates for their effective use as PAI contrast agents. These nanocapsules are made from FDA-approved, biodegradable materials and are designed to be stable in biological environments, addressing the issue of rapid dissociation seen in previous attempts. They are ~70 nm in size, optimal for cellular uptake. They can also be conjugated with targeting domains such as monoclonal antibodies specific to biomarkers like the epidermal growth factor receptor (EGFR), allowing for molecular-specific imaging. The encapsulated dye aggregates provide high contrast and sensitivity in imaging, enabling the detection of even single-digit numbers of cancer cells.

This technology is differentiated by its successful use of ICG J-aggregates, enhancing the effectiveness of PAI. The encapsulation of these dye aggregates within a biodegradable polymer shell addresses the stability issues that have plagued previous attempts at using J-aggregates for imaging. The use of PEG-PLGA polymersomes provides additional benefits, such as resistance to protein opsonization and improved body clearance. Furthermore, the ability to conjugate these nanocapsules with targeting antibodies like anti-EGFR allows for highly specific targeting of cancer cells, improving the accuracy of imaging and the effectiveness of treatments.

The technology also demonstrates significant stability in biological environments, maintaining its properties for extended periods, which is crucial for practical clinical applications. The combination of these features makes this technology a promising tool for early detection and treatment of cancer, potentially improving patient outcomes through more precise and effective interventions.

Benefits

Uses FDA-approved and biodegradable materials
Enhanced photothermal stability and sharp near-infrared (NIR) absorption peaks. Photoacoustic imaging (PAI)-friendly with high specificity and sensitivity
Optimal size (~70 nm) for cellular uptake
Conjugation with targeting domains like monoclonal antibodies for molecular-specific imaging. Selective targeting of diseased cells, such as cancer cells
Demonstrated stability in serum for up to 24 hours, allowing ample imaging time and efficient clearance
High contrast and sensitivity in imaging, enabling detection of single-digit numbers of cancer cells