Photodynamic therapy is a promising alternative treatment modality that uses a photosensitizer to kill cancer cells through oxidative damage. However, many tumors contain regions of hypoxia, limiting the overall effectiveness of the technique. Therefore, an image-guided approach to improve tumor oxygenation during photodynamic therapy could result in better, more-reliable outcomes.
We have developed nanoparticles that act as ultrasound/photoacoustic imaging contrast agents while also delivering oxygen to these hypoxic tumor sites. The particles contain a perfluorocarbon (PFC) core which, when vaporized, creates an acoustic impedance difference between the particles and surround tissues, allowing the particles to be visualized with ultrasound imaging. In addition to its contrast enhancement, the PFC core is also a great carrier of oxygen, capable of delivering the payload to tumors. Hydrophobically modified indocyanine green dye (IGC) is added as the photosensitizer to absorb the optical energy from the nanosecond pulsed laser that is used to activate the particles and nucleate vaporization. Upon activation of the particles, a bolus of oxygen is released into the surrounding tissue. The release of oxygen can be quantified by imaging the tumor with spectroscopic photoacoustic imaging in real time. Finally, the encapsulated ICG dye can be leveraged to act as a photosensitizer for photodynamic therapy. Experiments show that physiologically relevant payloads of oxygen can be released from the particles on demand. Furthermore, we are able to visualize the vaporized particles with single-particle sensitivity. These results pave the way for improved image-guided photodynamic therapy.
Sidhartha Jandhyala, Austin C. Van Namen, and Geoffrey P. Luke, "Optically activated oxygen-loaded perfluorocarbon nanoparticles for ultrasound-guided photodynamic therapy (Conference Presentation)," Proc. SPIE 10476, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVII, 1047605 (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2288452.5751468301001.
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