A Nanoprobe for Diagnosing and Mapping Lymphatic Metastasis of Tumor Using 3D Multispectral Optoacoustic Tomography Owing to Aggregation/Deaggregation Induced Spectral Change

Abstract

Lymphatic metastasis of tumor is one of leading causes of cancer-related death, and diagnosing lymphatic metastasis is of significance in terms of optimal disease management and possible better outcomes for patients. Herein a turn-on optoacoustic nanoprobe is reported for noninvasively diagnosing and locating lymphatic metastasis in vivo. A positively charged tricyanofuran-containing polyene chromophore (TCHM) with high extinction coefficient is designed, synthesized, and allowed to form the nanoprobe with a negatively charged hyaluronan. The TCHMs take an aggregated state within the nanoprobe and exhibit weak absorption at 882 nm, the overexpressed hyaluronidase in cancer cells specifically degrades hyaluronan into small fragments and disaggregates TCHMs, thereby greatly enhancing the absorption at 882 nm and generating prominent optoacoustic signals. For multispectral optoacoustic tomography (MSOT) imaging in vivo, mice models with subcutaneous tumor and orthotopic bladder tumor are imaged first to demonstrate the nanoprobe's capability for detecting HAase-overexpressing tumors. A mouse model of lymphatic metastasis of tumor is then established and the lymphatic metastasis is successfully imaged and tracked optoacoustically. The imaging results were verified using multiple biochemical assays. Moreover, 3D MSOT renderings are obtained for precisely locating and tracking the metastasis of tumor in lymphatic system in a spatiotemporal manner.The rationale for HAase detection is described as follows:The presence of HAase degrades the HA and causes the disintegration of the nanoprobe, thereby releasing the positively charged chromophore molecules and turning their aggregated state into the deaggregated one. Consequently, enhanced optoacoustic signal is achieved owing to the deaggregation-induced

Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

“…At present, the clinical gold standard used to detect SLNs is labelling with blue dye or a radioactive nanocolloid and then performing SLNB. Although various nanoprobes based on different imaging modalities have been developed to map the metastatic status of SLNs [12][13][14][15][34][35][36] , few can distinguish T-MLNs from Inf-LNs. Tumour cell infiltration and proliferation of immune cells due to the induction of inflammatory factors result in the enlargement of SLNs 37 , usually leading to misidentification and unnecessary removal of benign SLNs during surgical resection 38 inflammation should be determined before SLN resection to reduce potential complications caused by unnecessary resection.…”

“…PAM is a rapidly developing imaging technology, and all types of nanoscale agents have been comprehensively explored as PA imaging probes to map SLNs 34 , 47 – 49 . Luke et al introduced EGFR-targeted plasmonic nanosensors (MAPS), which can noninvasively and effectively identify oral squamous cell carcinoma sLN micrometastases from normal LNs by using ultrasound-guided spectroscopic photoacoustic (sPA) imaging 50 .…”

A tumor microenvironment–induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy

“…Photoacoustic (PA) imaging is a novel biomedical imaging technique based on the combination of photoexcitation and ultrasonic detection (1)(2)(3)(4)(5). Because the attenuation of acoustic waves in biological tissues is two to three orders of magnitude lower than that of light waves, PA imaging of biological tissues provides excellent contrast, superspace resolution, high penetration, and high sensitivity (6)(7)(8).…”

Recent Progress in the Development of Multifunctional Nanoplatform for Precise Tumor Phototherapy

“…In addition, the expression of hyaluronidase (HAase) increases in the tumor microenvironment during the premetastatic stage of the tumor, and then promotes the degradation of the tumor matrix and accelerate the metastasis of tumor cells. [89] Liao and co-workers developed a charge-reversed nanosystem with HAase and pH dual response characteristics for tumor cells targeted PA delivery. [90] The preparation of this nanosystem is use of FA and dopamine-modified HA to coat positively charged nanoparticles (<30 nm) formed by self-assembly of amphiphilic peptides.…”