As renal fibrosis nanotherapeutics, the endogenous biomaterial melanin not only has natural biocompatibility and biodegradability but also has inherent photoacoustic imaging ability and certain anti-inflammatory effects. These properties determine that melanin can not only as a carrier of medication but also track the biodistribution and renal uptake of drugs in vivo by photoacoustic imaging in real-time. Curcumin is a natural compound with biological activity, which has excellent ROS scavenging ability and good anti-inflammatory property. These materials appear more advantages in the development of nanoscale diagnostic and therapeutic platforms for future clinical translation. Herein, this study developed curcumin-loaded melanin nanoparticles (MNP-PEG-CUR NPs) as an efficient medication delivery system for photoacoustic imaging guidance renal fibrosis treatment. The nanoparticles are about 10 nm in size, exhibit good renal clearance efficiency, excellent photoacoustic imaging ability, and good in vitro and in vivo biocompatibility. These preliminary results indicated that MNP-PEG-CUR have clinically applicable potential as a therapeutic nanoplatform for renal fibrosis.
Unravelling the pathophysiology of depression is a unique challenge. Depression is closely associated with reduced norepinephrine (NE) levels; therefore, developing bioimaging probes to visualize NE levels in the brain is a key to elucidating the pathophysiological process of depression. However, because NE is similar in structure and chemical properties to two other catecholamine neurotransmitters, epinephrine and dopamine, designing an NE-specific multimodal bioimaging probe is a difficult task. In this work, we designed and synthesized the first near-infrared fluorescent-photoacoustic (PA) dual-modality imaging probe for NE (FPNE). The β-hydroxyethylamine of NE was shown to react via nucleophilic substitution and intramolecular nucleophilic cyclization, resulting in the cleavage of a carbonic ester bond in the probe molecule and release of a merocyanine molecule (IR-720). This process changed the color of the reaction solution from blue-purple to green, and the absorption peak was red-shifted from 585 to 720 nm. Under light excitation at 720 nm, linear relationships between the concentration of NE and both the PA response and the fluorescence signal intensity were observed. Thus, the use of intracerebral in situ visualization for diagnosis of depression and monitoring of drug interventions was achieved in a mouse model by fluorescence and PA imaging of brain regions after administration of FPNE by tail-vein injection.
Imaging skeletal muscle function and metabolism, as reported by local hemodynamics and oxygen kinetics, can elucidate muscle performance, severity of an underlying disease or outcome of a treatment. Herein, we used multispectral optoacoustic tomography (MSOT) to image hemodynamics and oxygen kinetics within muscle during exercise. Four healthy volunteers underwent three different hand-grip exercise challenges (60-sec isometric, 120-sec intermittent isometric and 60-sec isotonic). During isometric contraction, MSOT showed a decrease of HbO2, Hb and total blood volume (TBV), followed by a prominent increase after the end of contraction. Corresponding hemodynamic behaviors were recorded during the intermittent isometric and isotonic exercises. A more detailed analysis of MSOT readouts revealed insights into arteriovenous oxygen differences and muscle oxygen consumption during all exercise schemes. These results demonstrate an excellent capability of visualizing both circulatory function and oxygen metabolism within skeletal muscle under exercise, with great potential implications for muscle research, including relevant disease diagnostics.
Multispectral optoacoustic tomography (MSOT) holds great promise as a non-invasive diagnostic tool for inflammatory bowel diseases. Yet, reliability and the impact of physiological processes during fasting and after food intake on optoacoustic signals have not been studied. In the present investigator initiated trial (NCT05160077) the intestines of ten healthy subjects were examined by MSOT at eight timepoints on two days, one fasting and one after food intake. While within-timepoint and within-day reproducibility were good for single wavelength 800 nm and total hemoglobin (ICC 0.722-0.956), between-day reproducibility was inferior (ICC -0.137 to 0.438). However, temporal variability was smaller than variation between individuals (coefficients of variation 8.9%-33.7% vs. 17.0%-48.5%). After food intake and consecutive increased intestinal circulation, indicated by reduced resistance index of simultaneous Doppler ultrasound, optoacoustic signals did not alter significantly. In summary, this study demonstrates high reliability and temporal stability of MSOT for imaging the human intestine during fasting and after food intake.
Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.
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.
Tumor-specific targeting and tumor visualization are major obstacles for clinical diagnosis and treatment. Herein, a dual-targeted “all-in-one” nanoplatform (FAA@CM) for trimodal imaging-guided photothermal/chemodynamic synergistic therapy was successfully synthesized by encapsulating Fe3O4, Ag2S, and ascorbic acid with the 4T1 cell membrane. The dual-targeting capability derived from 4T1 cell membrane cloaking and magnetic targeting enables the highly precise tumor-specific delivery of FAA@CM. Fe2+ released from FAA@CM in a weakly acidic tumor microenvironment can trigger the Fenton reaction to achieve chemodynamic therapy (CDT). The photothermal performance of FAA@CM not only enables photothermal therapy but also promotes the CDT effect. In order to relieve H2O2 deficiency, a biosafe H2O2 prodrug, ascorbic acid, was introduced to greatly increase the H2O2 concentration in tumors, promoting the Fenton reaction to produce more •OH to enhance the oxidative damage to tumors. Interestingly, FAA@CM exhibits trimodal imaging capabilities, including second near-infrared (NIR-II, 1000-1700 nm) fluorescence imaging, photoacoustic imaging, and magnetic resonance imaging, which can guide the laser irradiation, achieving complete elimination of 4T1 tumors in BALB/c mice. This work provided a novel dual-targeted, multifunctional theranostic nanoplatform for highly effective tumor therapy.
Objective: To explore the metabolic characteristics of arthritis and enthesitis using multispectral opto-acoustic tomography (MSOT), a technology using near-infrared multispectral laser to stimulate tissues and detect the emitted acoustic energy, enabling non-invasive quantification of tissue components in vivo based on differential absorbance at multiple wavelengths.
Methods: We performed a cross-sectional study in patients with RA or PsA and healthy controls (HCs). Participants underwent clinical, ultrasonographic and MSOT examination of MCP and wrist joints as well as the entheses of the common extensor tendon at the lateral humeral epicondyles and of the patellar, quadriceps and Achilles tendon. MSOT-measured haemoglobin (Hb), oxygen saturation, collagen and lipid levels were quantified and scaled mean differences between affected and unaffected joints and entheses were calculated as defined by clinical examination or ultrasonography using linear mixed effects models.
Results: We obtained 1535 MSOT and 982 ultrasonography scans from 87 participants (34 PsA, 17 RA, 36 HCs). Entheseal tenderness was not associated with significant metabolic changes, whereas enthesitis-related sonographic changes were associated with increased total Hb, oxygen saturation and collagen content. In contrast, the presence of arthritis-related clinical and sonographic findings showed increased Hb levels, reduced oxygen saturation and reduced collagen content. Synovial hypertrophy was associated with increased lipid content in the joints.
Conclusion: MSOT allows determination of distinct metabolic differences between arthritis and enthesitis in a non-invasive setting in humans in vivo.