Organic single molecule based nano-platform for NIR-II imaging and chemo-photothermal synergistic treatment of tumor.

Integrating multiple functionalities of near-infrared second window fluorescence imaging (NIR-Ⅱ FLI), chemotherapy, and photothermal treatment (PTT) into a single molecule is desirable but still a highly challenging task. Herein, inspired by the results that hyperthermia can enhance the cytotoxicity of some alkylating agents, we designed and synthesized the novel compound NM. By introducing nitrogen mustard's active moiety bis(2-chlorethyl)amino into Donor-Acceptor-Donor (D-A-D) electronic structure, the unimolecular system not only behaviored as a chemotherapeutic agent but also exhibited good PTT and NIR-Ⅱ FLI abilities. The hydrophobic agent NM was encapsulated by DSPE-PEG2000 to generate the nano-platform NM-NPs. The current study on in vitro and in vivo experiments indicated that NM-NPs make vessels visualize clearly in the NIR-II zone and achieve complete tumor elimination through chemo-photothermal synergistic treatment. Overall, this study provides a new innovative strategy for developing superior, versatile phototheranostics for cancer theranostics.

Acceptor engineering for NIR-II dyes with high photochemical and biomedical performance.

It is highly important and challenging to develop donor-acceptor-donor structured small-molecule second near-infrared window (NIR-II) dyes with excellent properties such as water-solubility and chem/photostability. Here, we discovery an electron acceptor, 6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline (TQT) with highest stability in alkaline conditions, compared with conventional NIR-II building block benzobisthiadiazole (BBT) and 6,7-diphenyl-[1,2,5] thiadiazolo[3,4-g]quinoxaline (PTQ). The sulfonated hydrophilic dye, FT-TQT, is further synthesized with 2.13-fold increased quantum yield than its counterpart FT-BBT with BBT as acceptor. FT-TQT complexed with FBS is also prepared and displays a 16-fold increase in fluorescence intensity compared to FT-TQT alone. It demonstrates real-time cerebral and tumor vessel imaging capability with µm-scale resolution. Dynamic monitoring of tumor vascular disruption after drug treatment is achieved by NIR-II fluorescent imaging. Overall, TQT is an efficient electron acceptor for designing innovative NIR-II dyes. The acceptor engineering strategy provides a promising approach to design next generation of NIR-II fluorophores which open new biomedical applications.

Liver injury long-term monitoring and fluorescent image-guided tumor surgery using self-assembly amphiphilic donor-acceptor NIR-II dyes.

Real-time monitoring of liver dysfunction represents a significant unmet demand in clinical and preclinical research. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescent imaging is an attractive method for biomedical imaging and may be a promising approach for liver dysfunction monitoring. Herein, we designed and synthesized a small-molecule NIR-II dye TQT 1009 with an asymmetric donor-acceptor (D-A) core. By introducing four kinds of polyethylene glycol (PEG) with different length and molecular weights (nK, n = 0.5, 2, 5, 10) to TQT1009, the dye was self-assembled into different nanoparticles named as TQP nK with regulated size and controllable circulation lifetime in vivo. In general, TQP nK showed a super high contrast ratio for blood vessels, bones, intestines, lymph, and tumor imaging. The best-selected probe, TQP 10K, exhibited ultralong in vivo circulation time (>96 h) which was suitable for long-term quantitative monitoring of liver and vessel function at a single dose, implying the excellent prospects compared with ICG, which was quickly eliminated in blood within a few minutes. Meanwhile, TQP 10K also achieved NIR-II surgical navigation of tumor in an extended time window (>7 d). Overall, our results demonstrate the self-assembly PEGylated amphiphilic TQP nK provide a new probe design strategy for liver function monitoring and image-guided tumor surgery in a prolonged time window.