RESUMEN
Photoacoustic (PA) imaging has emerged as a powerful technique for the high resolution visualization of biological processes within deep tissue. Through the development and application of exogenous targeted contrast agents and activatable probes that can respond to a given cancer biomarker, researchers can image molecular events in vivo during cancer progression. This information can provide valuable details that can facilitate cancer diagnosis and therapy monitoring. In this tutorial review, we provide a step-by-step guide to select a cancer biomarker and subsequent approaches to design imaging agents for in vivo use. We envision this information will be a useful summary to those in the field, new members to the community, and graduate students taking advanced imaging coursework. We also highlight notable examples from the recent literature, with emphasis on the molecular designs and their in vivo PA imaging performance. To conclude, we provide our outlook and future perspective in this exciting field.
Asunto(s)
Neoplasias , Técnicas Fotoacústicas , Medios de Contraste , Humanos , Imagen Molecular , Sondas Moleculares , Neoplasias/diagnóstico por imagenRESUMEN
Shortwave infrared (SWIR) dyes are characterized by their ability to absorb light from 900 to 1400â nm, which is ideal for deep tissue imaging owing to minimized light scattering and interference from endogenous pigments. An approach to access such molecules is to tune the photophysical properties of known near-infrared dyes. Herein, we report the development of a series of easily accessible (three steps) SWIR xanthene dyes based on a dibenzazepine donor conjugated to thiophene (SCR-1), thienothiophene (SCR-2), or bithiophene (SCR-3). We leverage the fact that SCR-1 undergoes a bathochromic shift when aggregated for in vivo studies by developing a ratiometric nanoparticle for NO (rNP-NO), which we employed to successfully visualize pathological levels of nitric oxide in a drug-induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Our work demonstrates how easily this dye series can be utilized as a component in nanosensor designs for imaging studies.
Asunto(s)
Óxido Nítrico , Técnicas Fotoacústicas , Técnicas Fotoacústicas/métodos , Xantenos , Diagnóstico por Imagen/métodos , Colorantes Fluorescentes , Imagen ÓpticaRESUMEN
Nitric oxide (NO) generated within the tumor microenvironment is an established driver of cancer progression and metastasis. Recent efforts have focused on leveraging this feature to target cancer through the development of diagnostic imaging agents and activatable chemotherapeutics. In this context, porphyrins represent an extraordinarily promising class of molecules, owing to their demonstrated use within both modalities. However, the remodeling of a standard porphyrin to afford a responsive chemical that can distinguish elevated NO from physiological levels has remained a significant research challenge. In this study, we employed a photoinduced electron transfer strategy to develop a panel of NO-activatable porphyrin photosensitizers (NOxPorfins) augmented with real-time fluorescence monitoring capabilities. The lead compound, NOxPorfin-1, features an o-phenylenediamine trigger that can effectively capture NO (via N2O3) to yield a triazole product that exhibits a 7.5-fold enhancement and a 70-fold turn-on response in the singlet oxygen quantum yield and fluorescence signal, respectively. Beyond demonstrating excellent in vitro responsiveness and selectivity toward NO, we showcase the potent photodynamic therapy (PDT) effect of NOxPorfin-1 in murine breast cancer and human non-small cellular lung cancer cells. Further, to highlight the in vivo efficacy, two key studies were executed. First, we utilized NOxPorfin-1 to ablate murine breast tumors in a site-selective manner without causing substantial collateral damage to healthy tissue. Second, we established a nascent human lung cancer model to demonstrate the unprecedented ability of NOxPorfin-1 to halt tumor growth and progression completely. The results of the latter study have tremendous implications for applying PDT to target metastatic lesions.
Asunto(s)
Neoplasias Pulmonares , Fotoquimioterapia , Porfirinas , Humanos , Animales , Ratones , Óxido Nítrico , Porfirinas/farmacología , Porfirinas/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Neoplasias Pulmonares/tratamiento farmacológico , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Metal ions are indispensable to all living systems owing to their diverse roles. Perturbation of metal homeostasis have been linked to many pathological conditions. As such, visualizing metal ions in these complex environments are of utmost importance. Photoacoustic imaging is a promising modality that combines the sensitivity of fluorescence to the superior resolution of ultrasound, through a light-in sound-out process, making it an appealing modality for metal ion detection in vivo. In this review, we highlight recent advances in the development of photoacoustic imaging probes for in vivo detection of metal ions, such as potassium, copper, zinc, and palladium. In addition, we provide our perspective and outlook on the exciting field.
Asunto(s)
Técnicas Fotoacústicas , Técnicas Fotoacústicas/métodos , Metales , Cobre , Zinc , IonesRESUMEN
Background: In 1948, the synthesis and Plasmodium lophurae activity of 2-hydroxy-1,4-naphthoquinones containing 3-alkyldiarylether side chains was reported. Method/results: The synthesis of five related compounds, designed to be more metabolically stable, was pursued. The compounds were synthesized using a radical alkylation reaction with naphthoquinones. One compound had a lower IC50 value against various strains of Plasmodium falciparum and assay data indicate that it binds to the Qo site of cytochrome bc1. With a low yield for the radical alkylation of the most active compound, a reductive alkylation method with used to improve reaction yields. Conclusion: Further synthetic knowledge was obtained, and the assay data indicate that there are sensitivity differences between avian and human malarial parasites for these molecules.
Malaria is a disease caused by a parasite that affects millions of people each year and results in many deaths. In 1948, 300 structurally related compounds were made and tested for antimalarial activity with the goal of finding a drug to treat the disease. From this work, promising compounds were identified and this work has served as a starting point for further investigations. Based on recent discoveries, this study made variations of promising 1948 compounds to investigate whether antimalarial activity could be improved. These compounds were made using two different methods. One derivative was found to be more potent than the original compound but was not the one expected based on the 1948 work.