Multimodality imaging is highly desirable for accurate diagnosis by achieving high sensitivity, spatial–temporal resolution, and penetration depth with a single structural unit. However, it is still challenging to integrate fluorescent (FL) and plasmonic modalities into a single structure, as they are naturally incompatible because of significant FL quenching by plasmonic noble-metal nanoparticles. We developed a new class of silver@AIEgen (aggregation-induced emission luminogen) core–shell nanoparticles for multimodality imaging in living cells and animals. In addition to the excellent FL property of the AIEgen shell, dark-field microscopy (DFM) and computed tomography (CT) imaging modalities were successfully integrated into the probe via an AgNP core. It resolved the challenges of in...[ Read more ]

Multimodality imaging is highly desirable for accurate diagnosis by achieving high sensitivity, spatial–temporal resolution, and penetration depth with a single structural unit. However, it is still challenging to integrate fluorescent (FL) and plasmonic modalities into a single structure, as they are naturally incompatible because of significant FL quenching by plasmonic noble-metal nanoparticles. We developed a new class of silver@AIEgen (aggregation-induced emission luminogen) core–shell nanoparticles for multimodality imaging in living cells and animals. In addition to the excellent FL property of the AIEgen shell, dark-field microscopy (DFM) and computed tomography (CT) imaging modalities were successfully integrated into the probe via an AgNP core. It resolved the challenges of integrating FL and plasmonic materials in a single structure with preserved properties. The superior AIE fluorescence together with the high signal-to-noise ratio of DFM and the deep penetration depth of CT modalities offer great promise for advanced diagnostic applications. Nanomaterials with integrated multiple imaging and therapeutic modalities possess great potentials in accurate cancer diagnostics and enhanced therapeutic efficacy. Traditional strategies for achieving multimodality nanoplatform through one by one combination of different modalities are challenged by the complicated structural design and fabrication as well as inherent incompatibility between different modalities. Herein, a novel strategy is presented to realize multimodal imaging and synergistic therapy using this simple silver core/AIEgen shell nanoparticles. In addition to the intrinsic FL and metal-based CT and radiation therapy (RT) properties, an extra functionality at the core/shell interface was identified to enable excellent photothermal (PT) and photoacoustic (PA) performance. As a result, five imaging and therapy modalities (FL, PA, CT, photothermal therapy (PTT), and RT) were achieved with a single structural unit for sensitive tumor imaging and effective therapy.

Simultaneously, RNA interference (RNAi) is demonstrated as one of the most powerful technologies for sequence-specific suppression of abnormal genes in cancer therapeutics. Exploration of novel vehicles for small interfering RNA (siRNA) delivery with high efficiency, low cytotoxicity and self-monitoring functionality is persistently pursued. By taking advantage of the above AIE-featured core@shell nanovehicles, we applied them for high-efficiency siRNA delivery and real-time monitoring of its intracellular behaviors. The thickness of AIE shell was optimized to achieve the best performance in target interference and tumor growth inhibition in vitro and in vivo. By harnessing the unique AIE fluorescence, real-time visualization of the cellular uptake and release of siRNA and long-term tracking of in vivo tumor tissue were also successfully demonstrated. Outperforming to the commercial transfection reagents, the higher efficiency and reproducibility in target regulation as well as lower cytotoxicity represent the prospective future of this nanovehicle in RNAi-based therapeutic application.

On the other hand, sensitive and accurate detection of highly contagious virus is urgently demanded for disease diagnosis and treatment. A convenient dual-modality readout immunoassay platform based on a multifunctional AIEgen for highly sensitive and specific detection of virus by integrating of FL and plasmonic colorimetry in a single detection system was designed. The multifunctional AIEgen with enzyme cleavage sites could be hydrolyzed by virus immunobridged alkaline phosphatase (ALP), with production of strong emissive AIE aggregates. And at the same time, Ag⁺ could be reduced to an in situ shell on the surface of AuNP with an obvious color change for naked-eye observation. Further by taking advantage of the magnetic enrichment, EV71 virions can be specifically assayed with a detection limit down to 1.4 copies/μL. Even more importantly, this dual-modality immunoassay can be applied for real clinical sample diagnosis. The multifunctional AIEgen, dual-signal readout, excellent quantitatively capability, high sensitivity and strong anti-interference ability collectively construct a promising platform for both convenient preliminary screening and high-accuracy clinic diagnosis of virus.

Stereoisomers have attracted drastic interests in pharmaceutic development and chiral optical engineering. A series of trans/cis AIEgens with huge difference in optical properties, self-assembly mode and bio-activity were reported herein. That is one of the trans/cis couple is emissive with high quantum yield, while the other one is non-emissive. Their structures are identified by single-crystal X-ray diffraction. Under UV irradiation, the trans/cis couples could transform to each other with strong and weak FL emission. Analysis by solid-state nucleic magnetic resonance (NMR) and single crystal structures helps illustrate the cause of the difference in FL emission. The application of these trans/cis AIE probes in cell imaging to achieve super-resolution imaging performance with light-up FL signal under irradiation was demonstrated. Further, the trans/cis AIEgens displayed different conversion rate under enzyme catalysis with huge variation in toxicity to living cells. The huge difference in optical properties and bioactivities caused by such small mutation in molecular structure would deepen the perspective of relationship between structure and functionality.