Yang Li,Jianfeng Gao,Shuping Wang,Mingxia Du,Xiaowen Hou,Tian Tian,Xue Qiao,Zhiquan Tian,Peter J. Stang,Shijun Li,Xuechuan Hong,Yuling Xiao
Complete excision of the last remaining 1–2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEGnk (n = 1, 2, 5) as new-generation NIR-II (1000–1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window (48–144 h). This study highlights the potential of using L6-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.
Pancreatic cancer, a highly aggressive solid tumor, presents multiple challenges in treatment. Although surgical resection is the primary treatment for early-stage non-metastatic cases, the deep abdominal location of the pancreas complicates precise intraoperative localization, adversely affecting surgical outcomes and patient prognosis. To address these clinical challenges, we aim to develop an innovative intraoperative navigation platform for precision tumor-targeted delivery. We systematically evaluated the tumor-targeting specificity and tissue-penetrating capacity of three hydrosoluble polymers, i.e., dextran, PEG, and HA, in pancreatic carcinoma models. The uptake kinetics of these materials in cancer cells and their penetration dynamics across complex tumor matrices were quantitatively evaluated via in vitro assays and three-dimensional tumor spheroid models. Complementary in vivo validation involved the use of PNAC-1 cell subcutaneous xenograft models to map the spatiotemporal distribution and tumoral accumulation of the lead candidates. Results demonstrated that dextran-FITC had a superior tumor-targeting performance, showing a significantly higher fluorescence intensity than PEG-FITC and HA-FITC. These preliminary data reveal significant heterogeneity in the intertumoral localization efficiency among the polymer carriers, establishing a mechanistic foundation for intraoperative navigation. Through rational optimization of carrier selection and delivery modalities, this platform aims to enhance surgical precision, minimize off-target effects, and ultimately improve clinical outcomes.
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