This work presents the establishment of novel bright-emission small-molecule NIR-II fluorophores for in vivo tumor imaging and NIR-II image-guided sentinel lymph node surgery.

Novel biocompatible NIR-II aggregation-induced emission dots are facilely assembled and used for NIR-II biomedical fluorescence imaging.

NIR-II fluorophores have shown great promise for biomedical applications with superior in vivo optical properties. To date, few small-molecule NIR-II fluorophores have been discovered with donor-acceptor-donor (D-A-D) or symmetrical structures, and upconversion-mitochondria-targeted NIR-II dyes have not been reported. Herein, we report development of D-A type thiopyrylium-based NIR-II fluorophores with frequency upconversion luminescence (FUCL) at ~580 nm upon excitation at ~850 nm. H4-PEG-PT can not only quickly and effectively image mitochondria in live or fixed osteosarcoma cells with subcellular resolution at 1 nM, but also efficiently convert optical energy into heat, achieving mitochondria-targeted photothermal cancer therapy without ROS effects. H4-PEG-PT has been further evaluated in vivo and exhibited strong tumor uptake, specific NIR-II signals with high spatial and temporal resolution, and remarkable NIR-II image-guided photothermal therapy. This report presents the first D-A type thiopyrylium NIR-II theranostics for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and excellent photothermal efficiency.

The first small-molecule based αvβ3-targeted NIR-II/PET dual-modal probes via base-catalyzed thiol-addition chemistry were concisely assembled and evaluated.

The development of novel biodegradable and nontoxic fluorophores that integrate diagnosis and therapy for effective cancer treatment has obtained tremendous attention in the past decades. In this report, water-soluble and biocompatible small-molecule near-infrared II (NIR-II) fluorescent dye H2a-4T complexed with fetal bovine serum (FBS) and Cetuximab proteins with excellent optical properties and targeting ability is prepared. High spatial and temporal resolution imaging of hind limb vasculature and the lymphatic system of living mice using H2a-4T@FBS complex is demonstrated in precise NIR-II imaging-guided sentinel lymph node surgery. More importantly, H2a-4T@Cetuximab complex not only exhibits a remarkable cell-killing ability but also achieves highly active tumor targeting efficiency for epidermal growth factor receptor, overexpressing colorectal cancer which is beneficial to in vivo NIR-II fluorescent imaging-guided photothermal therapy of colon tumors. To the best of our knowledge, it is the first time that the concept of light-harvesting complex is exploited for enhancing the NIR-II signals and photothermal energy conversion in molecule-protein complex theranostic agent, making them a promising candidate for future clinical applications in cancer theranostics.

Traditional luminescent materials including fluorescent probes suffer from notorious aggregation‐caused quenching in aqueous solutions. Although several approaches such as the aggregation‐induced emission effect have been developed, it remains a significant challenge to identify an effective and efficient strategy to resolve this issue. Herein, quaternary ammonium salts Q8PBn and Q8PNap as a novel class of bright near infrared window II (NIR‐II, 1000–1700 nm) probes are designed and synthesized, and the twisted intramolecular charge transfer formation at the excited state can be effectively suppressed for the newly designed probes. Furthermore, Q8PNap complexation with fetal bovine serum (Q8PNap/FBS) significantly increases the quantum yield by ≈32‐fold compared with PEGylated tertiary amine Q8P, and Q8PNap/FBS is successfully used to achieve high spatial and temporal resolution imaging of hind limb vasculature, lymphatic system, and small tumor metastasis, as well as precise NIR‐II imaging‐guided tumor and lymph node surgery in small animal models for the first time.

A novel NIR-II small-molecule fluorophore HQL2 for in vivo NIR-IIa and NIR-IIb vascular and tumor vessel imaging.

Immunotherapy with immune checkpoint blockade (ICB) has shown limited benefits in hepatocellular carcinoma (HCC) and other cancers, mediated in part by the immunosuppressive tumor microenvironment (TME). As p53 loss of function may play a role in immunosuppression, we herein examine the effects of restoring p53 expression on the immune TME and ICB efficacy. We develop and optimize a CXCR4-targeted mRNA nanoparticle platform to effectively induce p53 expression in HCC models. Using p53-null orthotopic and ectopic models of murine HCC, we find that combining CXCR4-targeted p53 mRNA nanoparticles with anti-PD-1 therapy effectively induces global reprogramming of cellular and molecular components of the immune TME. This effect results in improved anti-tumor effects compared to anti-PD-1 therapy or therapeutic p53 expression alone. Thus, our findings demonstrate the reversal of immunosuppression in HCC by a p53 mRNA nanomedicine when combined with ICB and support the implementation of this strategy for cancer treatment.