Near-infrared Photoacoustic Imaging Research Articles

Laser-Synthesized Germanium Nanoparticles as Biodegradable Material for Near-Infrared Photoacoustic Imaging and Cancer Phototherapy.

Biodegradable nanomaterials can significantly improve the safety profile of nanomedicine. Germanium nanoparticles (Ge NPs) with a safe biodegradation pathway are developed as efficient photothermal converters for biomedical applications. Ge NPs synthesized by femtosecond-laser ablation in liquids rapidly dissolve in physiological-like environment through the oxidation mechanism. The biodegradation of Ge nanoparticles is preserved in tumor cells in vitro and in normal tissues in mice with a half-life as short as 3.5 days. Biocompatibility of Ge NPs is confirmed in vivo by hematological, biochemical, and histological analyses. Strong optical absorption of Ge in the near-infrared spectral range enables photothermal treatment of engrafted tumors in vivo, following intravenous injection of Ge NPs. The photothermal therapy results in a 3.9-fold reduction of the EMT6/P adenocarcinoma tumor growth with significant prolongation of the mice survival. Excellent mass-extinction of Ge NPs (7.9 L g-1 cm-1 at 808nm) enables photoacoustic imaging of bones and tumors, following intravenous and intratumoral administrations of the nanomaterial. As such, strongly absorbing near-infrared-light biodegradable Ge nanomaterial holds promise for advanced theranostics.

Preparation of near-infrared photoacoustic imaging and photothermal treatment agent for cancer using a modifiable acid-triggered molecular platform.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.

The location of metastatic lymph nodes and the evaluation of lymphadenectomy by near-infrared photoacoustic imaging with iridium complex nanoparticles.

Histopathology evaluation and lymphadenectomy of node-positive patients is the usual procedure in clinical therapy. However, it requires days for the histopathology result analysis, which impedes intraoperative decision-making and immediate treatment. Noninvasive real-time imaging of metastatic lymph nodes can overcome these defects and help medical workers evaluate lymph nodes and make the operation decision more efficiently. Herein we developed iridium(III)-cyanine complex/bovine serum albumin (BSA)-based nanoparticles which are conjugated with folic acid (FA) (IrCy-FA NPs). The synthesized IrCy-FA NPs exhibit good biocompatibility, strong near-infrared absorption, and impressive lymph node accumulation and can serve as a photoacoustic (PA) imaging probe for lymph node imaging. Besides, the lymph nodes enriched with IrCy-FA NPs showing green color are easily visible to the naked eye, suggesting their potential as an intraoperative indicator. The real-time PA imaging with excellent contrast and high spatial resolution can promote efficient and reliable quantitative analysis of lymph nodes in vivo. By employing IrCy-FA NPs as the PA agent for lymph node imaging, we achieve effective pre-operative and post-operative evaluations of metastatic lymph nodes in lymphadenectomy. This study may provide helpful information for PA imaging guided colocalization and evaluation of lymph nodes and facilitate this method towards clinical trials.

Size-tunable ICG-based contrast agent platform for targeted near-infrared photoacoustic imaging.

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional information of tissues with high resolution. Although NIR-PAI is promising, its widespread use is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represents an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agents with tunable size down to 230 nm and direct functionalization with targeting moieties. The ICG-JA platform has a detectable PA signal in vitro that is two times stronger than whole blood and high photostability. The targeting ability of ICG-JA was measured in vitro using HeLa cells. The ICG-JA platform was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 min post-injection with a contrast-to-noise ratio of 2.42.

Benzobisthiadiazole and Its Derivative-Based Semiconducting Polymer Nanoparticles for Second Near-Infrared Photoacoustic Imaging.

Photoacoustic (PA) imaging has received more and more attention on disease diagnosis and fundamental scientific research. It is still challenging to amplify their imaging ability and reduce the toxicity of inorganic materials and exogenous contrast agents. Semiconducting polymer nanoparticles (SPNs), as a new type of contrast agent, have the advantages of low toxicity, flexible structure adjustment, good photostability, and excellent photothermal conversion efficiency. SPNs containing benzo(1,2-c;4,5-c′)bis(1,2,5)thiadiazole (BBT) units, as the most classic second near-infrared window (NIR-II, 1,000–1700 nm) PA contrast agents, can achieve light absorption in the NIR-II region, thereby effectively reducing light loss in biological tissues and improving imaging resolution. This mini review summarizes the recent advances in the design strategy of BBT and its derivative-based semiconducting polymer nanoparticles for second near-infrared photoacoustic imaging. The evolution process of BBT blocks provides a unique perspective for the design of high-performance NIR-II PA contrast agents.

Large π-extended donor-acceptor polymers for highly efficient in vivo near-infrared photoacoustic imaging and photothermal tumor therapy

Large π-extended donor-acceptor polymers for highly efficient in vivo near-infrared photoacoustic imaging and photothermal tumor therapy

Apoferritin-Engineered Nanoprobe for Tumor-Targeted Triple-NIR Imaging and Phototherapy.

Considering that pathological hallmarks are directly related to structural and chemical information of tumor, noninvasive, real-time, spatially resolved quantitative chemical imaging is significant for treatment decisions. The discovery of the transparency window of biological tissues and the advancement of near-infrared technology provide exciting prospects for in vivo imaging. Herein, an engineering apoferritin-conjugated cypate nanoprobe is fabricated for near-infrared photoacoustic imaging and fluorescence imaging in the first and second window. As the analogue of indocyanine green, dicarboxylic cypate is directly conjugated with the apoferritin molecules for forming assembly nanoprobes. Resulting from the intrinsic targeting and optical capacity of the nanoprobes, the triple near-infrared imaging can perform multimeasurements of the target analyte in real-time. This imaging methodology not only provides the structural background information of the tumor, each pixel also contains quantitative in situ information of the tumor. In particular, part of the absorbed light energy is released as heat energy in the near-infrared photoacoustic imaging process. The constructed triple near-infrared nanoprobes therefore naturally navigate the photothermal treatment plan of tumor and finally realize the efficient assistance of tumor photothermal ablation. The tumor metabolomics reveal that the nanoprobe-assisted tumor ablation has a potential mechanism toward glutamine- and phenylalanine-related metabolism perturbation and the disordered oxidative stress state. The tumor-specific bioconjugate nanoprobes hold great potential as a versatile theranostic platform for tumor imaging and therapy.

Alkaline phosphatase-triggered self-assembly of near-infrared nanoparticles for the enhanced photoacoustic imaging of tumors.

In this chapter, we discuss the need for the development of enzyme-activatable probes in the field of tumor-targeted photoacoustic (PA) imaging, then we give a brief description of the innovation of designing alkaline phosphatase (ALP)-activatable probes for PA imaging. After that, we provide detailed protocols for the syntheses and characterizations of a near-infrared photoacoustic imaging probe, 1P, developed in our research group. With this tool, 1P could form nanoparticles 1-NPs under the catalysis of ALP and thus could be used to enhance PA imaging both in vitro and in vivo.

Biocompatible ring-deformed indium phthalocyanine label for near-infrared photoacoustic imaging

Photoacoustic imaging of small animals plays an increasingly important role in preclinical studies and is poised to become a valuable diagnostic imaging tool for a large diversity of human diseases. Exogenous contrast agents absorbing in the near-infrared (NIR) window where tissues are most transparent (650–950 nm) may help to increase the resolution and sensitivity of photoacoustic imaging, and may also offer specificity to targeted tissues. We show that a ring-deformed indium phthalocyanine (InPc) with a strong absorption band at ~840 nm is a promising photoacoustic probe, while presents adequate photostability for imaging, very fast and efficient radiationless processes, and negligible cytotoxicity or phototoxicity in vitro up to concentrations of 30 µM. The sensitivity of its photoacoustic detection was demonstrated by following the time-dependence of InPc uptake in a monolayer of 4T1-luc2 cells in vitro. In vivo imaging using a commercial photoacoustic tomography equipment confirmed the ability to detect InPc in 4T1-luc2 tumors orthotopically inoculated in the mammary gland female BALB/c mice (8–12 weeks old) within a few minutes of its intravenous administration. InPc remained in the tumor for hours and proved to be biocompatible.

RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

HighlightsA narrow bandgap electron donor–acceptor (D–A) semiconducting polymer nanoparticle (SPN) coated with red blood cell membrane (RBCM) for photoacoustic imaging and photothermal therapy.The D–A structure endows SPN with excellent near-infrared absorbance, high photothermal conversion ability, and good photothermal stability.The RBCM endows SPN with good biocompatibility, prolonged blood circulation, and improved tumor accumulation, while the small size structure endows SPN with deep tumor penetration and rapid clearance from body.

Indocyanine Green J Aggregates in Polymersomes for Near-Infrared Photoacoustic Imaging

Clinical translation of photoacoustic imaging (PAI) has been limited by the lack of near-infrared (NIR) contrast agents with low toxicity required for regulatory approval. Herein, J aggregates of indocyanine green (ICG) with strong NIR absorbance were encapsulated at high loadings within small 77 nm polymersomes (nanocapsules) composed of poly(lactide-co-glycolide-b-poly(ethylene glycol)) (PLGA-b-PEG) bilayers, thus enabling PAI of of breast and ovarian cancer cells with high specificity and a sensitivity at the level of ∼100 total cells. All of the major components of the polymersomes are FDA approved and used in the clinic. During formation of polymersomes with a water-in-oil-in-water double emulsion process, loss of ICG from the ICG J aggregates was minimized by coating them with a layer of branched polyethylenimine and by providing excess "sacrificial" ICG to adsorb at the oil-water interfaces. The encapsulated J aggregates were protected against dissociation by the polymersome shell for 24 h in 100% fetal bovine serum, after which the polymersomes biodegraded and the J aggregates dissociated to ICG monomers.

Recent Progress on Near-Infrared Photoacoustic Imaging: Imaging Modality and Organic Semiconducting Agents.

Over the past few decades, the photoacoustic (PA) effect has been widely investigated, opening up diverse applications, such as photoacoustic spectroscopy, estimation of chemical energies, or point-of-care detection. Notably, photoacoustic imaging (PAI) has also been developed and has recently received considerable attention in bio-related or clinical imaging fields, as it now facilitates an imaging platform in the near-infrared (NIR) region by taking advantage of the significant advancement of exogenous imaging agents. The NIR PAI platform now paves the way for high-resolution, deep-tissue imaging, which is imperative for contemporary theragnosis, a combination of precise diagnosis and well-timed therapy. This review reports the recent progress on NIR PAI modality, as well as semiconducting contrast agents, and outlines the trend in current NIR imaging and provides further direction for the prospective development of PAI systems.

Enhanced near-infrared photoacoustic imaging of silica-coated rare-earth doped nanoparticles

Near-infrared photoacoustic (PA) imaging is an emerging diagnostic technology that utilizes the tissue transparent window to achieve improved contrast and spatial resolution for deep tissue imaging. In this study, we investigated the enhancement effect of the SiO2 shell on the PA property of our core/shell rare-earth nanoparticles (REs) consisting of an active rare-earth doped core of NaYF4:Yb,Er (REDNPs) and an undoped NaYF4 shell. We observed that the PA signal amplitude increased with SiO2 shell thickness. Although the SiO2 shell caused an observed decrease in the integrated fluorescence intensity due to the dilution effect, fluorescence quenching of the rare earth emitting ions within the REDNPs cores was successfully prevented by the undoped NaYF4 shell. Therefore, our multilayer structure consisting of an active core with successive functional layers was demonstrated to be an effective design for dual-modal fluorescence and PA imaging probes with improved PA property. The result from this work addresses a critical need for the development of dual-modal contrast agent that advances deep tissue imaging with high resolution and signal-to-noise ratio.

Synthesis and characterization of an HSP27-targeted nanoprobe for in vivo photoacoustic imaging of early nerve injury

Abstract Imaging is routinely used for clinical and diagnostic purposes, but techniques capable of high specificity and resolution for the early detection of nerve injury are still limited. In this study, we found that heat shock protein 27 (HSP27) becomes highly upregulated within 3 to 7 days of nerve injury. Taking advantage of this expression pattern, we conjugated gold nanorods (GNRs) to HSP27-specific antibodies to generate a nanoprobe (GNR-HSP27Abs) that could be targeted to the site of nerve injury and detected by near-infrared photoacoustic imaging. Notably, photoacoustic images acquired 12hours after local administration of GNR-HSP27Abs demonstrated that the nanoprobe can distinguish between injured and uninjured nerves in rats. Taken together, these findings expand the application of nanoprobe-targeted photoacoustic imaging to the detection of injured nerves, and prompt further development of this novel imaging platform for clinical application.

Synthesis and characterization of an HSP27-targeted nanoprobe for in vivo photoacoustic imaging of early nerve injury

Imaging is routinely used for clinical and diagnostic purposes, but techniques capable of high specificity and resolution for the early detection of nerve injury are still limited. In this study, we found that heat shock protein 27 (HSP27) becomes highly upregulated within 3 to 7 days of nerve injury. Taking advantage of this expression pattern, we conjugated gold nanorods (GNRs) to HSP27-specific antibodies to generate a nanoprobe (GNR-HSP27Abs) that could be targeted to the site of nerve injury and detected by near-infrared photoacoustic imaging. Notably, photoacoustic images acquired 12hours after local administration of GNR-HSP27Abs demonstrated that the nanoprobe can distinguish between injured and uninjured nerves in rats. Taken together, these findings expand the application of nanoprobe-targeted photoacoustic imaging to the detection of injured nerves, and prompt further development of this novel imaging platform for clinical application.

A dual-functional benzobisthiadiazole derivative as an effective theranostic agent for near-infrared photoacoustic imaging and photothermal therapy.

Nanoparticles (NPs) with integrated functionalities of targeting, therapy, imaging contrast and biocompatibility have shown promise for application in improved disease diagnosis and therapy. Herein, we report a theranostic agent based on a narrow-bandgap small molecule, benzo[1,2-c;4,5-c']bis[1,2,5]thiadiazole-4,7-bis(9,9-dioctyl-9H-fluoren-2-yl)thiophene (denoted as BBT-2FT), with the strong absorption of near-infrared (NIR) light. Colloidal nanoparticles composed of BBT-2FT showed a photoacoustic signal intensity ten times higher than that of blood, and high photothermal conversion efficiency (η = 40%) under the irradiation of 808 nm laser light, which killed over 90% of HeLa cells in 10 min.

Ultrathin Gold Nanowire-Functionalized Carbon Nanotubes for Hybrid Molecular Sensing

Carbon nanotubes (CNTs) have shown great potential as sensing component in the electrochemical field effect transistor and optical sensors, because of their extraordinary one-dimensional electronic structure, thermal conductivity, and tunable and stable near-infrared emission. However, the insolubility of CNTs due to strong van der Waals interactions limits their use in the field of nanotechnology. In this study, we demonstrate that noncovalent ultrathin gold nanowires functionalized multiwalled carbon nanotube (GNW-CNT) hybrid sensing agents show highly efficient and selective immune molecular sensing in electrochemical and near-infrared photoacoustic imaging methods. A detection limit of 0.01 ng/mL for the alpha-fetoprotein (AFP) antigen with high selectivity is shown. The extraordinary optical absorption, thermal, and electric conductivity of hybrid GNW-CNTs presented in this study could be an effective tactic to integrate imaging, sensing, and treatment functionalities.