The integration of high-performance fluorescent agents with advanced imaging modalities has revolutionized the landscape of cancer diagnostics and surgical intervention. This study presents a comprehensive investigation into thienothiadiazole-based nanoparticles (TTDT-TF NPs) as a potent platform for image-guided cancer surgery and theranostic applications in the second near-infrared window (NIR-II, 1000–1700 nm). By incorporating a novel electron-deficient core—4,6-di(2-thienyl)thieno[3,4-c][1,2,5]thiadiazole (TTDT)—into a donor-acceptor-donor (D-A-D) architecture, two organic dyes were synthesized: TTDT-TF and TTDT-TSF. Among these, TTDT-TF demonstrated superior optical properties, including NIR-II emission at 1011 nm, high fluorescence quantum yield (0.712%), and strong molar absorption coefficient (10.20 L·g⁻¹·cm⁻¹), making it ideal for deep-tissue visualization.
To enable systemic administration and enhance biocompatibility, TTDT-TF was formulated into water-dispersible nanoparticles using amphiphilic mPEG-DSPE via nanoprecipitation. The resulting nanoparticles exhibited a hydrodynamic diameter of approximately 120 nm, spherical morphology, and excellent colloidal stability in physiological buffers. These NPs maintained intense fluorescence emission at 1051 nm under 808 nm laser excitation, with a signal intensity nearly 1.5 times higher than that of TTDT-TSF NPs, attributed to reduced aggregation-induced quenching (ACQ) and optimized molecular packing.CD57 Antibody MedChemExpress
In vivo imaging revealed exceptional performance across multiple anatomical regions. After intravenous injection in healthy rats, clear visualization of brain, abdominal, and hind limb vasculature was achieved with high signal-to-background ratios (SBR > 8.MYL9 Antibody MedChemExpress 33).PMID:35147477 Cross-sectional analysis confirmed sub-millimeter spatial resolution, with full width at half-maximum values below 0.15 mm. Notably, the maximum penetration depth reached up to 8 mm, demonstrating the capability of NIR-II imaging to visualize structures beyond the reach of conventional techniques.
The tumor-targeting potential was evaluated in a 4T1 breast cancer mouse model. Within 5 hours post-injection, a significant increase in fluorescence signal was observed at the tumor site, peaking at 36 hours due to the enhanced permeability and retention (EPR) effect. Ex vivo imaging at 48 hours confirmed strong tumor-specific accumulation, with minimal signal in normal organs such as liver, spleen, and kidney, indicating favorable biodistribution and potential for renal clearance.
Most importantly, TTDT-TF NPs enabled precise delineation of tumor margins during real-time imaging, providing surgeons with a clear visual guide for complete resection while sparing healthy tissue. The high contrast and sharp edge definition significantly reduce the risk of residual tumor cells, enhancing surgical outcomes. Furthermore, the robust photostability of TTDT-TF NPs—retaining over 90% of initial fluorescence after prolonged irradiation—ensures reliable signal maintenance throughout extended procedures.
These findings establish TTDT-TF NPs as a highly effective theranostic agent combining diagnostic imaging with therapeutic guidance. Their ability to deliver bright, stable, and tumor-selective signals positions them as an ideal candidate for intraoperative imaging, enabling real-time decision-making and improving the accuracy and safety of cancer surgery. As a result, this work not only advances the field of NIR-II bioimaging but also paves the way for next-generation platforms that seamlessly integrate diagnosis and intervention in precision oncology.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com