Listening for the therapeutic window: Advances in drug delivery utilizing photoacoustic imaging

Abstract

The preclinical landscape of photoacoustic imaging has experienced tremendous growth in the past decade. This non-invasive imaging modality augments the spatiotemporal capabilities of ultrasound with optical contrast. While it has principally been investigated for diagnostic applications, many recent reports have described theranostic delivery systems and drug monitoring strategies using photoacoustics. Here, we provide an overview of the of the progress to date while highlighting work in three specific areas: theranostic nanoparticles, real-time drug monitoring, and stem cell ("living drug") tracking. Additionally, we discuss the challenges that remain to be addressed in this burgeoning field.

Photoacoustic monitoring of angiogenesis predicts response to therapy in healing wounds

“…Hand‐held scans using the LED‐based PA system allows easy mapping of wounds on contoured surfaces such as the ankle, thus making it ideal to visualise angiogenesis in complex wounds. The 850‐nm excitation used in this study falls within the biological optical window and maximises depth penetration while maintaining a relatively high signal‐to‐noise ratio (~35 dB) 50 . Limitations of this LED‐based system include a small cache: The system acquires 500–1500 frames per scan but the processing software only exports 180 representative frames per scan (one exported frame for every eight acquired frames).…”

“…The 850-nm excitation used in this study falls within the biological optical window and maximises depth penetration while maintaining a relatively high signal-to-noise ratio ($35 dB). 50 Limitations of this LED-based system include a small cache: The system acquires 500-1500 frames per scan but the processing software only exports 180 representative frames per scan (one exported frame for every eight acquired frames). Hence, there is a large loss of data unless one scans multiple small areas separately.…”

Optothermal properties of plasmonic inorganic nanoparticles for photoacoustic applications

“…The use of sensitive probes has been particularly beneficial for the advancement of photoacoustic microscopy. In fact, several kinds of photoacoustic microscopy techniques already exist [ 20 ], that are being explored for an increasing number of medical applications [ 21 ], which vary from two-dimensional imaging to computer-aided tomography [ 22 ]. As photoacoustic signal generation occurs upon absorption of the excitation radiation, high absorption coefficients at the excitation wavelength are a favourable feature for PNPs when they are used as contrast agents in living organisms [ [23] , [24] , [25] , [26] ].…”

“…Nevertheless, the efficiency of the photophysical processes involved in heat generation can be conveniently evaluated – often in a quantitative way – by the use of photoacoustics as a spectroscopic tool. Finally, PAI and light-based therapeutic methods (PTT, photodynamic therapy, and more) can be combined in a fruitful manner [ 22 , 27 ], especially when suitable contrast agents are employed [ [28] , [29] , [30] ].…”

H2S-activatable near-infrared afterglow luminescent probes for sensitive molecular imaging in vivo

“…luorescence imaging probes are indispensable in biomedical research and clinical diagnosis owing to their low cost, simple operation, and noninvasiveness; these characteristics enable real-time detection of physiological and pathological processes at the molecular and cellular levels [1][2][3][4] . However, because fluorescence imaging requires real-time light excitation, the inevitable light absorption, scattering, and autofluorescence of biological tissues can limit penetration depth and elicit a low signal-to-background ratio (SBR), compromising the sensitivity for in vivo imaging [5][6][7] . Afterglow luminescent probes (also called persistent luminescent probes), which can trap excitation energy in defects and slowly release photons after cessation of light excitation, have recently emerged as promising tools for overcoming the limitations of fluorescence probes in biosensing and molecular imaging [8][9][10][11] .…”