Differentiating Aggressive from Nonaggressive Prostate Cancer Using Unconjugated Contrast Agents

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Oncology

Background:

• Prostate cancer assessment requires accurate tumor aggressiveness evaluation for treatment decisions.
• Multimodal imaging combining optical, ultrasound, and photoacoustic methods is gaining clinical interest.
• Developing effective contrast agents is crucial for advanced cancer detection.

Purpose of the Study:

• To investigate the cellular uptake of indocyanine green (ICG), ICG-loaded nanobubbles (ICG-NBs), and ICG-loaded microbubbles (ICG-MBs) in prostate cancer cell lines.
• To determine if these agents can differentiate cancer cell aggressiveness based on uptake.
• To identify the cellular internalization pathways for ICG-NBs.

Main Methods:

• Systematic investigation of cellular uptake across prostate cancer cell lines with varying aggressiveness (PC-3M > PC-3 > DU-145 > LNCaP).
• Concentration- and time-dependent assays for ICG, ICG-NBs, and ICG-MBs.
• Validation in breast, colorectal, and pancreatic cancer cells.
• Mechanistic studies to identify internalization pathways.

Main Results:

• ICG-NBs showed significantly higher uptake (5-fold) in highly metastatic PC-3M cells compared to less aggressive lines after 1 hour.
• ICG-MBs had minimal uptake, detectable only after 12 hours in aggressive cell lines.
• Free ICG showed negligible uptake initially but increased over time in all cell lines.
• ICG-NB uptake correlated positively with cancer cell metastatic potential across different cancer types.
• Macropinocytosis was identified as the primary uptake pathway for ICG-NBs.

Conclusions:

• Unconjugated ICG-NBs can selectively differentiate aggressive from indolent cancer phenotypes.
• ICG-NBs demonstrate potential as a multimodal contrast agent for cancer theranostics.
• The differential uptake highlights the utility of ICG-NBs in guiding personalized cancer treatment strategies.