The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.

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Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

Biophotonics as a highly interdisciplinary frontier often requires the assistance of optical agents to control the light pathways in cells, tissues and living organisms for specific biomedical applications. Organic semiconducting materials (OSMs) composed of π-conjugated building blocks as the optically active components have recently emerged as a promising category of biophotonic agents. OSMs possess common features including excellent optical properties, good photostability and biologically benign composition. This review summarizes the recent progress in the development of OSMs based on small-molecule fluorophores, aggregation-induced emission (AIE) dyes and semiconducting oligomer/polymer nanoparticles (SONs/SPNs) for advanced biophotonic applications. OSMs have been exploited as imaging agents to transduce biomolecular interactions into second near-infrared fluorescence, chemiluminescence, afterglow or photoacoustic signals, enabling deep-tissue ultrasensitive imaging of biological tissues, disease biomarkers and physiological indexes. By fine-tuning the molecular structures, OSMs can also convert light energy into cytotoxic free radicals or heat, allowing for effective cancer phototherapy. Due to their instant light response and efficient light-harvesting properties, precise regulation of biological activities using OSMs as remote transducers has been demonstrated for protein ion channels, gene transcription and protein activation. In addition to highlighting OSMs as a multifunctional platform for a wide range of biomedical applications, current challenges and perspectives of OSMs in biophotonics are discussed.

Development of organic semiconducting materials for deep-tissue optical imaging, phototherapy and photoactivation

Vibrational spectroscopy has been extensively applied to the study of molecules in gas phase, in condensed phase, and at interfaces. The transition from spectroscopy to spectroscopic imaging of living systems, which allows the spectrum of biomolecules to act as natural contrast, is opening new opportunities to reveal cellular machinery and to enable molecule-based diagnosis. Such a transition, however, involves more than a simple combination of spectrometry and microscopy. We review recent efforts that have pushed the boundary of the vibrational spectroscopic imaging field in terms of spectral acquisition speed, detection sensitivity, spatial resolution, and imaging depth. We further highlight recent applications in functional analysis of single cells and in label-free detection of diseases.

https://science.sciencemag.org/content/sci/350/6264/aaa8870.full.pdf

Vibrational spectroscopic imaging of living systems: An emerging platform for biology and medicine

Exploring and understanding biological and pathological changes are of great significance for early diagnosis and therapy of diseases. Optical sensing and imaging approaches have experienced major progress in this field. Particularly, an emergence of various functional optical nanoprobes has provided enhanced sensitivity, specificity, targeting ability, as well as multiplexing and multimodal capabilities due to improvements in their intrinsic physicochemical and optical properties. However, one of the biggest challenges of conventional optical nanoprobes is their absolute intensity-dependent signal readout, which causes inaccurate sensing and imaging results due to the presence of various analyte-independent factors that can cause fluctuations in their absolute signal intensity. Ratiometric measurements provide built-in self-calibration for signal correction, enabling more sensitive and reliable detection. Optimizing nanoprobe designs with ratiometric strategies can surmount many of the limitations encountered by traditional optical nanoprobes. This review first elaborates upon existing optical nanoprobes that exploit ratiometric measurements for improved sensing and imaging, including fluorescence, surface enhanced Raman scattering (SERS), and photoacoustic nanoprobes. Next, a thorough discussion is provided on design strategies for these nanoprobes, and their potential biomedical applications for targeting specific biomolecule populations (e.g. cancer biomarkers and small molecules with physiological relevance), for imaging the tumor microenvironment (e.g. pH, reactive oxygen species, hypoxia, enzyme and metal ions), as well as for intraoperative image guidance of tumor-resection procedures.

Ratiometric optical nanoprobes enable accurate molecular detection and imaging

The near-infrared window between 1000 and 1700 nm, commonly termed the "second near-infrared (NIR-II) window," has quickly emerged as a highly attractive optical region for biological imaging. In contrast to conventional imaging in the visible region between 400 and 700 nm, as well as in the first NIR (NIR-I) window between 700 and 900 nm, NIR-II biological imaging offers numerous merits, including higher spatial resolution, deeper penetration depth, and lower optical absorption and scattering from biological substrates with minimal tissue autofluorescence. Noninvasive imaging techniques, specifically NIR-II fluorescence and photoacoustic (PA) imaging, have embodied the attractiveness of NIR-II optical imaging, with several NIR-II contrast agents demonstrating superior performance to the clinically approved NIR-I agents. Consequently, NIR-II biological imaging has been increasingly explored due to its tremendous potential for preclinical studies and clinical utility. Herein, the progress of optical imaging in the NIR-II window is reported. Starting with highlighting the importance of biological imaging in the NIR-II spectral region, the emergence and latest development of various NIR-II fluorescence and PA imaging probes and their applications are then discussed. Perspectives on the promises and challenges facing this nascent yet exciting field are then given.

Recent Advances of Optical Imaging in the Second Near-Infrared Window

Thienoisoindigo-based semiconducting polymer with a strong near-infrared absorbance is synthesized and its water-dispersed nanoparticles (TSPNs) are investigated as a contrast agent for photoacoustic (PA) imaging in the second near-infrared (NIR-II) window (1000-1350 nm). The TSPNs generate a strong PA signal in the NIR-II optical window, where background signals from endogenous contrast agents, including blood and lipid, are at the local minima. By embedding a TSPN-containing tube in chicken-breast tissue, an imaging depth of more than 5 cm at 1064 nm excitation is achieved with a contrast-agent concentration as low as 40 µg mL-1 . The TSPNs under the skin or in the tumor are clearly visualized at 1100 and 1300 nm, with negligible interference from the tissue background. TSPN as a PA contrast in the NIR-II window opens new opportunities for biomedical imaging of deep tissues with improved contrast.

Semiconducting Polymer Nanoparticles for Centimeters-Deep Photoacoustic Imaging in the Second Near-Infrared Window.

Transformation optics has made a major contribution to the advancement of modern electromagnetism and related research assisted by the development of metamaterials. In this work, we applied this concept to the thermodynamics using the coordinate transformation to the time-dependent heat diffusion equation to manipulate the heat flux by predefined diffusion paths. Experimentally, we demonstrated a transient thermal cloaking device engineered with effective thermal materials and successfully hid a centimeter-sized vacuum cavity. A rescaled heat equation accounting for all the pertinent parameters of various ingredient materials was proposed to greatly facilitate the fabrication. Our results unambiguously demonstrate the practical possibility of implementing complex transformed thermal media with high accuracy and acquiring several unprecedented thermodynamic functions, which we believe will help to broaden the current research and pave a new path to manipulate heat for novel device applications. In this work, transformation optics technique was applied to the thermodynamic area by using the coordinate transformation to the time-dependent heat diffusion equation, which enables the manipulation of the heat flux by predefined diffusion paths. A transient thermal cloaking device engineered with effective thermal materials was experimentally demonstrated by hiding a centimeter-sized vacuum cavity. To facilitate the fabrication a rescaled heat equation taking into account of all the pertinent parameters of various ingredient materials was proposed to guide the practical design of complex transformed thermal devices. Metamaterials are complex materials carefully devised to exhibit specific properties that do not typically occur in nature. For example, in transformation optics, they can guide light along predefined paths to produce effects such as invisibility cloaking. In a Chinese-Swedish collaboration, Sailing He and co-workers have applied this same approach to thermodynamics to fabricate a thermal cloaking device. The researchers assembled constituent materials in a precise manner to form a centimeter-sized thermal cloak that successfully guided a heat flux along predefined diffusion paths. Such devices have previously been investigated but the calculations of these studies were based on the heat conduction equation, and the resulting heat manipulation could only be applied to materials in a thermostatic state. Instead, He and co-workers have taken into account the time-dependent rescaled heat diffusion equation, which uses anisotropic thermal diffusivity as the main factor, so that their multi-layered device can be implemented with high accuracy and works in a transient state.

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A transient thermal cloak experimentally realized through a rescaled diffusion equation with anisotropic thermal diffusivity

An unmet need exists in high-speed and highly-sensitive intraoperative assessment of breast cancer margin during conservation surgical procedures. Here, we demonstrate a multispectral photoacoustic tomography system for breast tumor margin assessment using fat and hemoglobin as contrasts. This system provides ~3 mm tissue depth and ~125 μm axial resolution. The results agreed with the histological findings. A high sensitivity in margin assessment was accomplished, which opens a compelling way to intraoperative margin assessment.

Assessing breast tumor margin by multispectral photoacoustic tomography

Infrared (IR) imaging has become a viable tool for visualizing various chemical bonds in a specimen. The performance, however, is limited in terms of spatial resolution and imaging speed. Here, instead of measuring the loss of the IR beam, we use a pulsed visible light for high-throughput, widefield sensing of the transient photothermal effect induced by absorption of single mid-IR pulses. To extract these transient signals, we built a virtual lock-in camera synchronized to the visible probe and IR light pulses with precisely controlled delays, allowing submicrosecond temporal resolution determined by the probe pulse width. Our widefield photothermal sensing microscope enabled chemical imaging at a speed up to 1250 frames/s, with high spectral fidelity, while offering submicrometer spatial resolution. With the capability of imaging living cells and nanometer-scale polymer films, widefield photothermal microscopy opens a new way for high-throughput characterization of biological and material specimens.

https://advances.sciencemag.org/content/advances/5/7/eaav7127.full.pdf

Lu Lan

Papers

Semiconducting Polymer Nanoparticles for Centimeters-Deep Photoacoustic Imaging in the Second Near-Infrared Window.

A transient thermal cloak experimentally realized through a rescaled diffusion equation with anisotropic thermal diffusivity

Assessing breast tumor margin by multispectral photoacoustic tomography

Assessing breast tumor margin by multispectral photoacoustic tomography

Ultrafast chemical imaging by widefield photothermal sensing of infrared absorption.