Molecular Engineering of NIR‐II/IIb Emitting AIEgen for Multimodal Imaging‐Guided Photo‐Immunotherapy

Abstract

In view of the great challenges related to the complexity and heterogeneity of tumors, efficient combination therapy is an ideal strategy for eliminating primary tumors and inhibiting distant tumors. A novel aggregation‐induced emission (AIE) phototherapeutic agent called T‐TBBTD is developed, which features a donor–acceptor–donor (D–A–D) structure, enhanced twisted molecule conformation, and prolonged second near‐infrared window (NIR‐II) emission. The multimodal imaging function of the molecule has significance for its treatment time window and excellent photothermal/photodynamic performance for multimode therapy. The precise molecular structure and versatility provide prospects for molecular therapy for anti‐tumor applications. Fluorescence imaging in the NIR‐II window offers advantages with enhanced spatial resolution, temporal resolution, and penetration depth. The prepared AIE@R837 NPs also have controllable performance for antitumor photo‐immunotherapy. Following local photo‐irradiation, AIE@R837 NPs generate abundant heat, and 1O2 directly kills tumor cells, induces immunogenic cell death (ICD) as a photo‐therapeutic effect, and releases R837, which enhances the synergistic effect of antigen presentation and contributes to the long‐lasting protective antitumor immunity. A bilateral 4T1 tumor model revealed that this photo‐immunotherapy can eliminate primary tumors. More importantly, it has a significant inhibitory effect on distant tumor growth. Therefore, this method can provide a new strategy for tumor therapy.

Donor–Acceptor–Donor Near-Infrared-II Aggregation-Induced Emission Luminogens (AIEgens) Encapsulated within Nanometer-Sized Exosomes for Tumor Imaging

“…Fluorescence imaging performed in the transparent second near-infrared (NIR-II, 1000–1700 nm) biowindow has recently been a powerful tool to directly visualize dynamic biological processes owing to its noninvasive damage control, real-time visualization, and high sensitivity and imaging resolution as well as deep tissue penetration and high signal-to-background ratio (SBR). − So far, tremendous fluorophores emitting within the NIR-II region, including inorganic and organic NIR-II fluorophores, have been reported for various biological imaging applications. − Notably, remarkable accomplishments have been made by organic NIR-II fluorophores due to their metal-free safety, ease of processability, and clinical translation. − However, when these inherent hydrophobic fluorophores were fabricated into nanoparticles (NPs) with an aggregated state for biological applications, they always suffer from a low NIR-II quantum yield (QY) because of the emission quenching resulting from the strong intermolecular interactions, termed as the aggregation-caused quenching (ACQ) effect. − Fortunately, as an alternative method, aggregation-induced emission (AIE), which was discovered by Tang et al, holds great potential to address the quenching problem. − To drive emission to the NIR-II window, AIE luminogens (AIEgens) are usually designed as donor–acceptor–donor (D–A–D) structures with typical molecular motors to suppresses the strong intermolecular interactions. − However, compared to the systematically well-explored near-infrared-I (NIR-I, 650–900 nm) AIEgens, the research on D–A–D-type NIR-II AIEgens received a snub, by contrast, owing to their lack of diversity and low AIE character (α AIE < 2, a value defined as the ratio of PL intensity at water fraction ( f w ) = 90% to that of f w = 0%), which has become a bottleneck in the bioimaging field. − …”

A high performance AIE-active sonosensitizer for efficient sonodynamic tumor therapy

“…Constructing a donor–acceptor (D–A) structure is the major developing trend to prepare organic sensitizers with proper energy gap for efficient ROS generation. 27 Moreover, the energy gap can be well-modulated by incorporating appropriate acceptor and donor moieties. Even though the detailed mechanism is still not well-defined, it has been demonstrated that the lower excited energy enables the higher ROS generation ability of sonosensitizers.…”

Controlled plasmon-induced nonlinear absorption and optical limiting in Al/PVP composite nanofibers

“…Each of these mechanisms requires a specific excitation wavelength that corresponds to the energy difference between the two energy levels at which the electron transition takes place. In semiconductors, this can be achieved by changing the effective band gap energy by doping due to the Moss Burstein effect 5 or by changing the composition, 6–8 while in molecules, the positions of the energy levels are modified by adding side groups 9 or changing the molecular configuration. 10 However, in all these cases, achieving a wide wavelength range that a NLA application can operate at various wavelengths is a formidable hurdle to overcome.…”