Article-Journal

Molecular theranostic platforms with precise molecular structure and multiple functions hold great promise for cancer therapy. Different from the current strategy to incorporate various components into single entities with the risk of compromised efficacy and poor reproducibility, herein, molecular aggregation-induced emission (AIE) photosensitizers with ingenious integration of AIE fluorophore and cisplatin are facilely synthesized for synergetic anticancer therapy. Through adjusting donor structures coordinated with a cisplatin moiety and balancing the hydrophobic–hydrophilic property, donor–acceptor strength, and intramolecular charge transfer effect, the newly designed AIE photosensitizer TNPT exhibits good cellular uptake with predominant mitochondria location of cancerous cells, high chemotherapeutic efficacy similar to that of cisplatin, and strong reactive oxygen species (ROS) generation capability better than that of chlorin e6 (Ce6). Importantly, TNPT demonstrates synergetic photodynamic and chemotherapy on C6 glioma cells, showing 2.4-fold more potency than cisplatin upon white light irradiation (15 J/cm2). Further cell cycle analysis and apoptosis assay indicate that the photodynamic and chemo-therapeutic functions of TNPT synergistically inhibit DNA replication and cause cell apoptosis. In addition, TNPT exhibits selective uptake on cancerous cells rather than normal cells, contributing to significantly lower cytotoxicity to normal cells as compared to free cisplatin. This study provides a facile strategy to design molecular theranostic agents.

Molecular theranostic platforms with precise molecular structure and multiple functions hold great promise for cancer therapy. Different from current strategy to incorporate various components into single entities with the risk of compromised efficacy and poor reproducibility, herein, molecular aggregation-induced-emission (AIE) photosensitizers with ingenious integration of AIE fluorophore and cisplatin are facilely synthesized for synergetic anticancer therapy. Through adjusting donor structures coordinated with cisplatin moiety and balancing the hydrophobic-hydrophilic prop-erty, donor-acceptor strength, and intramolecular charge transfer effect, the newly designed AIE photosensitizer TNPT exhibits good cellular uptake with predominant mitochondria location of cancerous cells, high chemotherapeutic efficacy similar to cisplatin, and strong reactive oxygen species (ROS) generation capability better than chlorin e6 (Ce6). Im-portantly, TNPT demonstrates synergetic photodynamic and chemo-therapy on C6 glioma cells, showing 2.4-fold more potent than cisplatin upon white light irradiation (15 J/cm2). Further cell cycle analysis and apoptosis assay indicate that the photodynamic and chemo-therapeutic functions of TNPT synergistically inhibit DNA replication and cause cell apop-tosis. In addition, TNPT exhibits selective uptake on cancerous cells rather than normal cells, contributing to significantly lower cytotoxicity to normal cells as compared to free cisplatin. This study provides a facile strategy to design molecular theranostic agents.

In order to promote the development of photodynamic therapy (PDT), undesired side effects like low tumor specificity and the “always-on” phenomenon should be avoided. An effective solution is to construct an adaptive photosensitizer that can be activated to generate reactive oxygen species (ROS) in the tumor microenvironment. Herein, we design and synthesize a supramolecular switch based on a host-guest complex containing a water-soluble pillar[5]arene (WP5) and an AIEgen photosensitizer (G). The formation of the host-guest complex WP5?G quenches the fluorescence and inhibits ROS generation of G. Benefitting from the pH-responsiveness of WP5, the binding site between G and WP5 changes in an acidic environment through a shuttle movement. Consequently, fluorescence and ROS generation of the host-guest complex can be switched on at pH 5.0. This work offers a new paradigm for the construction of adaptive photosensitizers by using a supramolecular method.

The performance of current multimodal imaging contrast agents is often constrained by the tunability of nanomaterial structural design. Herein, the influence of nanostructure on the overall imaging performance of a composite nanomaterial for multimodal imaging of brain tumors is studied. Newly designed near-infrared molecules (TC1) are encapsulated into nanocomposites with ultrasmall iron oxide nanoparticles (UIONPs), forming stable nanoagents for multimodal imaging and photothermal therapy (PTT). Through a modified nanoprecipitation method, the synthesis of nanocomposites denoted as HALF is realized, in which UIONPs are restricted to half of the nanosphere. Such a unique nanostructure that physically separates TC1 and UIONPs is found with capabilities of mitigating fluorescence quenching, preserving the good performance of photoacoustic imaging, and enhancing the magnetic resonance imaging signals. Decorated with a peptide ligand cRGD for better brain tumor targeting, HALF-cRGD is evaluated both in vitro and in vivo as imaging contrast agents and photothermal therapeutic agents. The good imaging performance and PTT effect of HALF-cRGD in mice models indicate that the rational design and control of nanostructures could optimize multimodal imaging performance using the same components.

Organic photothermal nanoagents are promising candidates for treating primary tumors and inhibiting metastasis. However, they often exhibit poor photostability, low absorptivity, or limited photothermal conversion efficiency (PCE). Herein, a facile molecular engineering approach to produce efficient organic photothermal molecules is demonstrated. By integrating donor–acceptor structure and molecular motors, a small molecule (TA1) is synthesized with large absorptivity (22.4 L g−1 cm−1), negligible reactive oxygen species generation, high PCE (84.8%), excellent photothermal stability, and good biocompatibility. Furthermore, microfluidics is used to thoroughly study the relationship between the size and process conditions, yielding small uniform nanoparticles (NPs) with a diameter of 44 nm. Importantly, TA1 NPs under near-infrared laser irradiation significantly suppressed primary breast tumor growth and metastasis, both in vitro and in vivo. This study shows that small organic molecule nanoparticles are promising candidates for future cancer nanomedicine.

Precise design of fluorescent molecules with desired properties has enabled the rapid development of many research fields. Among the different types of optically active materials, luminogens with aggregation-induced emission (AIEgens) have attracted significant interest over the past two decades. The negligible luminescence of AIEgens as a molecular species and high brightness in aggregate states distinguish them from conventional fluorescent dyes, which has galvanized efforts to bring AIEgens to a wide array of multidisciplinary applications. Herein, the useful principles and emerging structure–property relationships for precise molecular design toward AIEgens with desirable properties using concrete examples are revealed. The cutting-edge applications of AIEgens and their excellent performance in enabling new research directions in biomedical theranostics, optoelectronic devices, stimuli-responsive smart materials, and visualization of physical processes are also highlighted.

Owing to efficient singlet oxygen (1O2) generation in aggregate state, photosensitizers (PSs) with aggregation-induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high 1O2 generation efficiency, strong molar absorption in long-wavelength range and near-infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short-wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation-induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high 1O2 generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8, which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in 1O2 generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.

Diagnostics of cerebrovascular structures and microscopic tumors with intact blood–brain barrier (BBB) significantly contributes to timely treatment of patients bearing neurological diseases. Dual NIR-II fluorescence and photoacoustic imaging (PAI) is expected to offer powerful strength, including good spatiotemporal resolution, deep penetration, and large signal-to-background ratio (SBR) for precise brain diagnostics. Herein, biocompatible and photostable conjugated polymer nanoparticles (CP NPs) are reported for dual-modality brain imaging in the NIR-II window. Uniform CP NPs with a size of 50 nm are fabricated from microfluidics devices, which show an emission peak at 1156 nm with a large absorptivity of 35.2 L g−1 cm−1 at 1000 nm. The NIR-II fluorescence imaging resolves hemodynamics and cerebral vasculatures with a spatial resolution of 23 µm at a depth of 600 µm. The NIR-II PAI enables successful noninvasive mapping of deep microscopic brain tumors (<2 mm at a depth of 2.4 mm beneath dense skull and scalp) with an SBR of 7.2 after focused ultrasound-induced BBB opening. This study demonstrates that CP NPs are promising contrast agents for brain diagnostics.

Exogenous contrast-agent-assisted NIR-II optical-resolution photoacoustic microscopy imaging (ORPAMI) holds promise to decipher wide-field 3D biological structures with deep penetration, large signal-to-background ratio (SBR), and high maximum imaging depth to depth resolution ratio. Herein, NIR-II conjugated polymer nanoparticle (CP NP) assisted ORPAMI is reported for pinpointing cerebral and tumor vasculatures. The CP NPs exhibit a large extinction coefficient of 48.1 L g−1 at the absorption maximum of 1161 nm, with an ultrahigh PA sensitivity up to 2 µg mL−1. 3D ORPAMI of wide-field mice ear allows clear visualization of regular vasculatures with a resolution of 19.2 µm and an SBR of 29.3 dB at the maximal imaging depth of 539 µm. The margin of ear tumor composed of torsional dense vessels among surrounding normal regular vessels can be clearly delineated via 3D angiography. In addition, 3D whole-cortex cerebral vasculatures with large imaging area (48 mm2), good resolution (25.4 µm), and high SBR (22.3 dB) at a depth up to 1001 µm are clearly resolved through the intact skull. These results are superior to the recently reported 3D NIR-II fluorescence confocal vascular imaging, which opens up new opportunities for NIR-II CP-NP-assisted ORPAMI in various biomedical applications.

Photooxidation under sunlight has potential in organic synthesis, bacterial killing, and organic waste treatment. Photosensitizers (PSs) can play an important role in this process. High 1O2 generation efficiency and excellent photostability under sunlight, as well as easy recyclability are ideal properties for PSs, but are not easy to achieve simultaneously. Herein, a pure organic porous conjugated polymer PS, CPTF, shows great photostability, large specific surface area, and high 1O2 generation efficiency under sunlight for photooxidation. For the oxidation of aromatic aldehyde to aromatic acid, the PS catalyst shows excellent recyclability, and enables solvent-free reactions in high yields both under direct sunlight and simulated AM 1.5G irradiation. In addition, the successful application of CPTF as an antibacterial agent and organic waste decomposition under simulated AM 1.5G irradiation indicates the potential of CPTF in sunlight-induced waste water treatment.