Self-Adaptive Photodynamic-to-Photothermal Switch for Smart Antitumor Photoimmunotherapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) possess different merits in cancer phototherapy, but the tumor microenvironment becomes unfavorable during the phototheranostic progress. Herein, we report a self-adaptive cyanine derivative Cy5-TPA with the PDT-dominated state to PTT-dominated state autoswitch feature for enhanced photoimmunotherapy. The incorporation of rotatable triphenylamine (TPA) moiety renders Cy5-TPA with the temperature or intramolecular-motion regulated photoactivities, which shows preferable reactive oxygen species (ROS) generation at lower temperature while stronger photothermal conversion at higher ones. Such a promising feature permits the in situ switch from PDT-dominated state to PTT-dominated state along with intratumoral temperature increase during laser irradiation, which also works in line with the concurrently reduced intratumoral oxygen level, exhibiting a self-adaptive phototherapeutic behavior to maximize the phototherapeutic antitumor outcome. Most importantly, the self-adaptive PDT-dominated state to PTT-dominated state switch also facilitates the sequential generation and release of damage-associated molecular patterns during immunogenic cell death (ICD). Hence, Cy5-TPA demonstrates excellent photoimmunotherapy performance in ICD induction, dendritic cell maturation, and T cell activation for tumor eradication and metastasis inhibition.

Preparation of AIEgen-based near-infrared afterglow luminescence nanoprobes for tumor imaging and image-guided tumor resection.

Fluorescence imaging represents a vital tool in modern biology, oncology and biomedical applications. Afterglow luminescence (AGL), which circumvents the light scattering and tissue autofluorescence interference associated with real-time excitation source, shows remarkably increased imaging sensitivity and depth. Here we present a protocol for the design and synthesis of AGL nanoprobes with an aggregation-induced emission (AIE) effect to simultaneously red shift and amplify the afterglow signal for tumor imaging and image-guided tumor resection. The nanoprobe (AGL AIE dot) is composed of an enol ether format of Schaap's agent and a near-infrared AIE fluorogen (AIEgen) (tetraphenylethylene-phenyl-dicyanomethylene-4H-chromene, TPE-Ph-DCM) to suppress the nonradiative dissipation pathway. Pre-irradiating AGL AIE dots with white light could generate singlet oxygen to convert Schaap's agent to its 1,2-dioxetane format, thus initializing the AGL process. With the aid of AIEgen, the AGL shows simultaneously red shifted emission maximum (from ~540 nm to ~625 nm) and enhanced intensity (by 3.2-fold), facilitating better signal-to-background ratio, imaging sensitivity and depth. Intriguingly, the activated AGL can last for over 10 days. Compared with conventional approaches, our method provides a new solution to concurrently red shift and amplify afterglow signals for better in vivo imaging outcomes. The preparation of AGL AIE dots takes ~2 days, the in vitro characterization takes ~10 days (less than 1 day if not involving afterglow kinetic profile study) and the tumor imaging and image-guided tumor resection takes ~7 days. These procedures can be easily reproduced and amended after standard laboratory training in chemical synthesis and animal handling.

Bioconjugation and Reaction-Induced Tumor Therapy via Alkynamide-Based Thiol-Yne Click Reaction.

Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.

A biocompatible pure organic porous nanocage for enhanced photodynamic therapy.

Porphyrin-based photosensitizers have been widely utilized in photodynamic therapy (PDT), but they suffer from deteriorating fluorescence and reactive oxygen species (ROS) due to their close π-π stacking. Herein, a biocompatible pure organic porphyrin nanocage (Py-Cage) with enhanced both type I and type II ROS generation is reported for PDT. The porphyrin skeleton within the Py-Cage is spatially separated by four biphenyls to avoid the close π-π stacking within the nanocage. The Py-Cage showed a large cavity and high porosity with a Brunauer-Emmett-Teller surface area of over 300 m2 g-1, facilitating a close contact between the Py-Cage and oxygen, as well as the fast release of ROS to the surrounding microenvironment. The Py-Cage shows superb ROS generation performance over its precursors and commercial ones such as Chlorin E6 and Rose Bengal. Intriguingly, the cationic π-conjugated Py-Cage also shows promising type I ROS (superoxide and hydroxyl radicals) generation that is more promising for hypoxic tumor treatment. Both in vitro cell and in vivo animal experiments further confirm the excellent antitumor activity of the Py-Cage. As compared to conventional metal coordination approaches to improve PDT efficacy of porphyrin derivatives, the pure organic porous Py-Cage demonstrates excellent biocompatibility, which is further verified in both mice and rats. This work of an organic porous nanocage shall provide a new paradigm for the design of novel, biocompatible and effective photosensitizers for PDT.

A Cascade Strategy Boosting Hydroxyl Radical Generation with Aggregation-Induced Emission Photosensitizers-Albumin Complex for Photodynamic Therapy.

Effective photodynamic therapy (PDT) requires photosensitizers (PSs) to massively generate type I reactive oxygen species (ROS) in a less oxygen-dependent manner in the hypoxia tumor microenvironment. Herein, we present a cascade strategy to boost type I ROS, especially hydroxyl radical (OH·-), generation with an aggregation-induced emission (AIE) photosensitizer-albumin complex for hypoxia-tolerant PDT. The cationic AIE PS TPAQ-Py-PF6 (TPA = triphenylamine, Q = anthraquinone, Py = pyridine) contains three important moieties to cooperatively enhance free radical generation: the AIE-active TPA unit ensures the effective triplet exciton generation in aggregate, the anthraquinone moiety possesses the redox cycling ability to promote electron transfer, while the cationic methylpyridinium cation further increases intramolecular charge transfer and electron separation processes. Inserting the cationic TPAQ-Py-PF6 into the hydrophobic domain of bovine serum albumin nanoparticles (BSA NPs) could greatly immobilize its molecular geometry to further increase triplet exciton generation, while the electron-rich microenvironment of BSA ultimately leads to OH·- generation. Both experimental and theoretical results confirm the effectiveness of our molecular cationization and BSA immobilization cascade strategy for enhancing OH·- generation. In vitro and in vivo experiments validate the excellent antitumor PDT performance of BSA NPs, superior to the conventional polymeric encapsulation approach. Such a multidimensional cascade strategy for specially boosting OH·- generation shall hold great potential in hypoxia-tolerant PDT and related antitumor applications.

NIR light-driven pure organic Janus-like nanoparticles for thermophoresis-enhanced photothermal therapy.

Photothermal therapy (PTT) represents a promising noninvasive tumor therapeutic modality, but the current strategies for enhancing photothermal effect have been mainly based on promoting thermal relaxation or suppressing radiative dissipation process of excited energy, leaving little room for further improvement in photothermal effect. Herein, as a proof of concept, we report the thermophoresis-enhanced photothermal effect with pure organic Janus-like nanoparticles (Janus-like NPs) for PTT. The Janus-like NPs are eccentrically loaded with compactly J-aggregated photothermal molecules (DMA-BDTO), which show red-shifted absorption wavelength and inhibited radiative decay as compared to individual molecules. Under NIR irradiation, the asymmetric heat generation at particle surface endows Janus-like NPs the active thermophoresis, which further increases collisions and converts kinetic energy into thermal energy, and Janus-like NPs exhibit significantly elevated temperature as compared to conventional NPs with homogenously distributed DMA-BDTO. Both in vitro and in vivo results confirm such thermophoresis-enhanced photothermal effect for improved PTT. Our new strategy of thermophoresis-enhanced photothermal effect shall open new insights for improving photothermal-related tumor therapy.

Pure Organic AIE Nanoscintillator for X-ray Mediated Type I and Type II Photodynamic Therapy.

X-ray induced photodynamic therapy (X-PDT) circumvents the poor penetration depth of conventional PDT with minimal radio-resistance generation. However, conventional X-PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation-induced emission (AIE) nanoscintillator (TBDCR NPs) that can massively generate both type I and type II ROS under direct X-ray irradiation is reported for hypoxia-tolerant X-PDT. Heteroatoms are introduced to enhance X-ray harvesting and ROS generation ability, and AIE-active TBDCR exhibits aggregation-enhanced ROS especially less oxygen-dependent hydroxyl radical (HO•- , type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near-infrared fluorescence and massive singlet oxygen and HO•- generation under direct X-ray irradiation, which demonstrate excellent antitumor X-PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1 O2 and radicals (HO•- ) in response to direct X-ray irradiation, which shall provide new insights for designing organic scintillators with excellent X-ray harvesting and predominant free radical generation for efficient X-PDT.

Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise Therapy of Bacterial Infections.

Traditional antibacterial procedures are getting inefficient due to the emergence of antimicrobial resistance, which makes alternative treatments in urgent demand. However, the selectivity toward infectious bacteria is still challenging. Herein, by taking advantage of the self-directed capture of infectious bacteria by macrophages, we developed a strategy to realize precise in vivo antibacterial photodynamic therapy (APDT) through adoptive photosensitizer-loaded macrophage transfer. TTD with strong reactive oxygen species (ROS) production and bright fluorescence was first synthesized and was subsequently formulated into TTD nanoparticles for lysosome targeting. TTD-loaded macrophages (TLMs) were constructed by direct incubation of TTD nanoparticles with macrophages, in which the TTD was localized in the lysosomes to meet the captured bacteria in the phagolysosomes. The TLMs could precisely capture and eradicate bacteria while being activated toward the proinflammatory and antibacterial M1 phenotype upon light illumination. More importantly, after subcutaneous injection, TLMs could effectively inhibit bacteria in the infected tissue through APDT, leading to good tissue recovery from severe bacterial infection. Overall, the engineered cell-based therapeutic approach shows great potential in the treatment of severe bacterial infectious diseases.

BSA-AIE Nanoparticles with Boosted ROS Generation for Immunogenic Cell Death Immunotherapy of Multiple Myeloma.

The main obstacle of multiple myeloma (MM) therapy is the compromised immune microenvironment, which leads to MM relapses and extramedullary disease progression. In this study, a novel strategy is reported of enhanced immunogenic cell death (ICD) immunotherapy with aggregation-induced emission (AIE) photosensitizer-loaded bovine serum albumin (BSA) nanoparticles (referred as BSA/TPA-Erdn), which can activate T cells, convert the cold tumor to hot, and reverse T cell senescence to restore the immune microenvironment for MM treatment. Loading AIE photosensitizer into the hydrophobic domain of BSA proteins significantly immobilizes the molecular geometry, which massively increases reactive oxygen species (ROS) generation and elicits a promising ICD immune response. Employing a NOD-SCID IL-2receptor gamma null mice model with MM patients' monocytes, it is shown that BSA/TPA-Erdn can simulate human dentric cell maturation, activate functional T lymphocytes, and increase additional polarization and differentiation signals to deliver a promising immunotherapy performance. Intriguingly, for the first time, it is shown that BSA/TPA-Erdn can greatly reverse T cell senescence, a main challenge in treating MM. Additionally, BSA/TPA-Erdn can effectively recruit more functional T lymphocytes into MM tumor. As a consequence, BSA/TPA-Erdn restores MM immune microenvironment and shows the best MM tumor eradication performance, which shall pave new insights for MM treatment in clinical practices.

An Activatable Near-Infrared Afterglow Theranostic Prodrug with Self-Sustainable Magnification Effect of Immunogenic Cell Death.

Herein, we report an activatable near-infrared (NIR) afterglow theranostic prodrug that circumvents high background noise interference caused by external light excitation. The prodrug can release hydroxycamptothecin (HCPT) in response to the high intratumoral peroxynitrite level associated with immunogenic cell death (ICD), and synchronously activate afterglow signal to monitor the drug release process and cold-to-hot tumor transformation. The prodrug itself is an ICD inducer achieved by photodynamic therapy (PDT). PDT initiates ICD and recruits first-arrived neutrophils to secrete peroxynitrite to trigger HCPT release. Intriguingly, we demonstrate that HCPT can significantly amplify PDT-mediated ICD process. The prodrug thus shows a self-sustainable ICD magnification effect by establishing an "ICD-HCPT release-amplified ICD" cycling loop. In vivo studies demonstrate that the prodrug can eradicate existing tumors and prevent further tumor recurrence through antitumor immune response.

Size Optimization of Organic Nanoparticles with Aggregation-Induced Emission Characteristics for Improved ROS Generation and Photodynamic Cancer Cell Ablation.

Aggregation-induced emission (AIE) fluorogens provide new opportunities to promote efficient reactive oxygen species (ROS) production in aggregates, which represent the promising candidates to construct theranostic nanoparticles for photodynamic therapy (PDT), but the size effect has been rarely explored. Herein, a universal method to fabricate organic nanoparticles with controllable sizes is reported and it demonstrates that ≈45 nm is the optimal size of AIE nanoparticles for PDT. Different from conventional Ce6 nanoparticles which show largely reduced fluorescence and ROS generation with increasing nanoparticle size, AIE nanoparticles show gradually enhanced brightness and ROS generation upon increasing the sizes from 6 to ≈45 nm. Further increasing sizes could continue to intensify the nanoparticle's brightness at the expense of ROS production, with the optimal size for ROS generation being achieved at ≈45 nm. Both 2D monolayer cell and 3D multicellular spheroid experiments confirm that 45 nm AIE nanoparticles have the highest cellular uptake, the deepest penetration depth, and the best photodynamic killing effect. Such a study not only manifests the advantages of AIE photosensitizers, but also delivers the optimal size ranging for efficient PDT, which shall provide an attractive paradigm to guide the development of phototheranostic nanoparticles besides molecular design to further promote PDT applications.

Cationization-Enhanced Type I and Type II ROS Generation for Photodynamic Treatment of Drug-Resistant Bacteria.

Photodynamic therapy as an emerging phototheranostic approach holds great potential for antibacterial treatment, but is limited by compromised reactive oxygen species (ROS) generation in an aggregate and hypoxic microenvironment. Herein, we report a molecular cationization approach to boost the ROS, especially type I ROS generation of aggregation-induced emission (AIE) photosensitizers for photodynamic treatment of drug-resistant bacteria. Such cationization reinforces the electron-accepting ability of the cationic moiety, promotes intersystem crossing (ISC), and increases electron separation and transfer processes. The resultant CTBZPyI exhibits largely enhanced ROS generation ability with predominant hydroxyl radical generation over its neutral counterpart in aggregate. Moreover, cationization also confers CTBZPyI with the bacterial binding ability and a moderate bacterial inactivation ability in the dark. Further light irradiation leads to superb antibacterial performance, which largely promotes the healing process of a MRSA-infected wound. Such a cationization strategy is expected to be a general strategy for the design of highly effective type I photosensitizers for bacterial infection treatment.

Smart Tetraphenylethene-Based Luminescent Metal-Organic Frameworks with Amide-Assisted Thermofluorochromics and Piezofluorochromics.

Luminescent metal-organic frameworks (MOFs) are appealing for the design of smart responsive materials, whereas aggregation-induced emission (AIE) fluorophores with twisted molecular rotor structure provide exciting opportunities to construct MOFs with new topology and responsiveness. Herein, it is reported that elongating AIE rotor ligands can render the newly formed AIE MOF (ZnETTB) (ETTB = 4',4''',4''''',4'''''''-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1'-biphenyl]-3,5-dicarboxylic acid))) with more elasticity, more control for intramolecular motion, and specific amide-sensing capability. ZnETTB shows specific host-guest interaction with amide, where N,N-diethylformamide (DEF), as an example, is anchored through CH···O and CH···π bonds with Zn cluster and ETTB8- ligand, respectively. DEF anchoring reduces both the distortion level and the intramolecular motions of ETTB8- ligand to lead a blueshifted and intensified emission for DEF ∈ ZnETTB. Moreover, amide anchoring also affords the DEF ∈ ZnETTB with the excellent thermofluorochromic behavior, and further increases the piezofluorochromic sensitivity at low-pressure ranges on the basis of its elastic framework. This work is one of the rare examples of amide-responsive smart materials, which shall shed new lights on design of smart MOFs with twisted AIE rotors for further sensing and detection applications.

Effective Therapy of Drug-Resistant Bacterial Infection by Killing Planktonic Bacteria and Destructing Biofilms with Cationic Photosensitizer Based on Phosphindole Oxide.

Developing effective therapies to fight against biofilm-associated infection is extremely urgent. The complex environment of biofilm forces the bacteria to evade the elimination of antibiotics, resulting in recalcitrant chronic infections. To address this issue, a cationic antibacterial agent based on phosphindole oxide (ß-PM-PIO) is designed and prepared. The unique molecular structure endows ß-PM-PIO with aggregation-induced emission feature and efficient singlet oxygen generation ability. ß-PM-PIO shows excellent visual diagnostic function to planktonic bacteria and biofilm. In addition, owing to the synergistic effect of phototoxicity and dark toxicity, ß-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance. Notably, ß-PM-PIO also holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects. This work offers a promising platform to develop advanced antibacterial agents against multidrug-resistant bacterial infection.

Activatable Persistent Luminescence from Porphyrin Derivatives and Supramolecular Probes with Imaging-Modality Transformable Characteristics for Improved Biological Applications.

Persistent luminescence without excitation light and tissue autofluorescence interference holds great promise for biological applications, but is limited by available materials with long-wavelength emission and excellent clinical potential. Here, we report that porphyrin derivatives can emit near-infrared persistent luminescence over 60 min after cessation of excitation light or on interaction with peroxynitrite. A plausible mechanism of the successive oxidation of vinylene bonds was demonstrated. A supramolecular probe with a ß-sheet structure was constructed to enhance the tumor targeting ability and the photoacoustic and persistent luminescence signals. Such probes featuring light-triggered function transformation from photoacoustic imaging to persistent luminescence imaging permit advanced image-guided cancer surgery. Furthermore, peroxynitrite-activated persistent luminescence of the supramolecular probe also enables rapid and precise screening of immunogenic cell death drugs.

Cationization to boost both type I and type II ROS generation for photodynamic therapy.

The pursuing of photosensitizers (PSs) with efficient reactive oxygen species (ROS) especially type I ROS generation in aggregate is always in high demand for photodynamic therapy (PDT) and photoimmunotherapy but remains to be a big challenge. Herein, we report a cationization molecular engineering strategy to boost both singlet oxygen and radical generation for PDT. Cationization could convert the neutral donor-acceptor (D-A) typed molecules with the dicyanoisophorone-triphenylamine core (DTPAN, DTPAPy) to their A-D-A' typed cationic counterparts (DTPANPF6 and DTPAPyPF6). Our experiment and simulation results reveal that such cationization could enhance the aggregation-induced emission (AIE) feature, promote the intersystem crossing (ISC) processes, and increase the charge transfer and separation ability, all of which work collaboratively to promote the efficient generation of ROS especially hydroxyl and superoxide radicals in aggregates. Moreover, these cationic AIE PSs also possess specific cancer cell mitochondrial targeting capability, which could further promote the PDT efficacy both in vitro and in vivo. Therefore, we expect this delicate molecular design represents an attractive paradigm to guide the design of type I AIE PSs for the further development of PDT.

Porphyrin-Based Two-Dimensional Layered Metal-Organic Framework with Sono-/Photocatalytic Activity for Water Decontamination.

Water treatment is crucial to improve the water quality and reduce diarrheal and chronological diseases caused by excessive discharge of organic dyes and other waste. The development and expansion of efficient catalysts for the degradation and sterilization of organic dyes has attracted widespread attention. Herein, we report an example of a porphyrin-based two-dimensional layered metal-organic framework (MOF) (2DZnTcpp) and its efficient sono-/photocatalytic degradation of organic dyes and bactericidal activity. The dislocated layers effectively avoid close π-π stacking and provide a porous space for oxygen/water/dye contact. The introduction of Zn ions increases the spin orbital coupling through the heavy atom effect and promotes the intersystem crossing process for singlet oxygen generation. The effective ligand-to-metal charge transfer and the excessive open Zn catalytic sites also facilitate water splitting for hydroxyl radical generation. These features together promote the reactive oxygen species (ROS) generation of 2DZnTcpp under light illumination or ultrasound sonication. It is worth noting that the 2DZnTcpp with a high specific surface area and porosity shows efficient sono-/photocatalytic degradation of organic dye waste. Moreover, 2DZnTcpp could also largely inactivate Escherichia coli under light irradiation (the light power of 1 sun) or ultrasound sonication for 30 min with efficiencies over 99.99999%. This work provides an approach for the design and synthesis of MOF-based sono-/photocatalysts used in the purification and treatment of textile wastewater and is committed to the establishment of a more efficient, fast, and environmentally friendly catalytic system.

Recent Progress in Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy.

In modern medicine, precision diagnosis and treatment using optical materials, such as fluorescence/photoacoustic imaging-guided photodynamic therapy (PDT), are becoming increasingly popular. Photosensitizers (PSs) are the most important component of PDT. Different from conventional PSs with planar molecular structures, which are susceptible to quenching effects caused by aggregation, the distinct advantages of AIE fluorogens open up new avenues for the development of image-guided PDT with improved treatment accuracy and efficacy in practical applications. It is critical that as much of the energy absorbed by optical materials is dissipated into the pathways required to maximize biomedical applications as possible. Intersystem crossing (ISC) represents a key step during the energy conversion process that determines many fundamental optical properties, such as increasing the efficiency of reactive oxygen species (ROS) production from PSs, thus enhancing PDT efficacy. Although some review articles have summarized the accomplishments of various optical materials in imaging and therapeutics, few of them have focused on how to improve the phototherapeutic applications, especially PDT, by adjusting the ISC process of organic optics materials. In this review, we emphasize the latest advances in the reasonable design of AIE-active PSs with type I photochemical mechanism for anticancer or antibacterial applications based on ISC modulation, as well as discuss the future prospects and challenges of them. In order to maximize the anticancer or antibacterial effects of type I AIE PSs, it is the aim of this review to offer advice for their design with the best energy conversion.

Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle-Invasive Bladder Cancer.

The development of photothermal agents with high photothermal conversion efficiency (PCE) can help to reduce drug and laser dosage, but still remains a big challenge. Herein, a novel approach is reported to design photothermal agents with high PCE values by promoting nonradiative heat generation processes through the cooperation of twisted intramolecular charge transfer (TICT) and molecular motions. Within the designed molecule 2DMTT-BBTD, the tetraphenylethenes act as molecular rotors, the long alkyl chain grafted thiophene helps to twist the molecular geometry to facilitate TICT state formation and preserve molecular motions in aggregate, while the strong electron-withdrawing BBTD unit enhances TICT effect. 2DMTT-BBTD exhibits NIR-absorption and a high PCE value of 74.8% under 808 nm laser irradiation. Gambogic acid (GA) which surmounts tumor cell thermotolerance by inhibiting heat shock protein 90 (HSP90) expression is coloaded into the nanoparticles, RGD peptide is further introduced to the nanoparticle surface to improve tumor accumulation. The resultant nanoparticles facilitate the effective low-temperature hyperthermia therapy of muscle-invasive bladder cancer (MIBC) with minimal damage to surrounding heathy tissues. This work delivers a new design concept for development of highly efficient photothermal agents, which also provides a safer approach for noninvasive treatment of MIBC and other malignant tumors.

Recent advances of AIE light-up probes for photodynamic therapy.

As a new non-invasive treatment method, photodynamic therapy (PDT) has attracted great attention in biomedical applications. The advantages of possessing fluorescence for photosensitizers have made it possible to combine imaging and diagnosis together with PDT. The unique features of aggregation-induced emission (AIE) fluorogens provide new opportunities for facile design of light-up probes with high signal-to-noise ratios and improved theranostic accuracy and efficacy for image-guided PDT. In this review, we summarize the recent advances of AIE light-up probes for PDT. The strategies and principles to design AIE photosensitizers and light-up probes are firstly introduced. The application of AIE light-up probes in photodynamic antitumor and antibacterial applications is further elaborated in detail, from binding/targeting-mediated, reaction-mediated, and external stimuli-mediated light-up aspects. The challenges and future perspectives of AIE light-up probes in the PDT field are also presented with the hope to encourage more promising developments of AIE materials for phototheranostic applications and translational research.