Aggregation-induced Emission Photosensitizers Research Articles

A straightforward strategy to modulate ROS generation of AIE photosensitizers for type-I PDT

Type-I photodynamic therapy (PDT), valued for its reduced oxygen requirement, generates highly cytotoxic •OH radicals. However, conventional strategies for developing type-I photosensitizers (PSs) are complex and involve intricate organic synthesis. Herein, we present a novel strategy to alter the generation of reactive oxygen species (ROS) by simply manipulating the twisting degree of donor–acceptor (D−A) type aggregation-induced emission (AIE) PSs. Specifically, natural saturated fatty acids are employed to modulate the twisting state of AIE PSs, with higher doping ratios yielding more twisted structures and increased type-I ROS generation. In contrast, fatty acids with higher crystallinity promote planar structures and type-II ROS generation. Theoretical calculations suggest that AIE PSs with highly twisted structures lead to a prominent reduction in ΔEST and effective separation of electron−hole pairs, thereby favoring efficient intersystem crossing and charge transfer. The PDT system primarily driven by type-I ROS exhibits efficient bactericidal activity against clinically drug-resistant bacteria, which remarkably accelerates the recovery of bacteria-infected wounds in mice. This study demonstrates the first example of modulating ROS generation type by manipulating the twisting degree of D−A type AIE PSs, eliminating the need for intricate molecular design and organic synthesis. The proposed strategy opens up new avenues for advancing PDT applications.

Robust Natural Light-Absorbable and -Degradable AIE Photosensitizers for Fluorescence Labeling and Efficient Photodynamic Eradication of Algal Pollutants.

Current water pollution caused by the excessive proliferation of harmful algae urges green methods that can efficiently utilize natural light to treat algal pollution. Herein, a series of aggregation-induced emission (AIE) photosensitizers that can efficiently harness sunshine were synthesized for the environmentally friendly and biocompatible treatment of algal pollution. By tuning the number of thiophene units and the electron conjugation degree, the photosensitizers' absorptions were broadened to cover the whole visible light range. The positive charges guided photosensitizers to aggregate on algal cell surfaces, resulting in a turn-on fluorescence signal and robust reactive oxygen species generation under sunshine, thereby achieving fluorescence labeling and photodynamic eradication of algae. The eradication outcomes demonstrated that the AIE photosensitizers significantly outperformed the commercial algaecide ALG. At 20 ppm photosensitizers, 90.4% and 94.2% killing rates were achieved for C. reinhardtii and C. vulgaris, respectively, 2.8- and 3.6-fold higher than those from the same concentration of ALG. Excellent performances in inhibiting algae growth were also verified with efficiency superior to that of ALG. Importantly, the photosensitizers can self-degrade into biocompatible fragments under irradiation to avoid secondary pollution. The developed photosensitizers that possess sunshine convertibility and degradability provide an efficient tool for algal treatment, showing broad research and application prospects.

Bovine serum albumin framed activatable NIR AIE photosensitizer for targeted tumor therapy

Organic near-infrared (NIR) photosensitizers (PS) largely facilitate photodynamic therapy (PDT). To overcome aggregation induced quenching and diminishment of reactive oxygen species (ROS) generation capability of NIR-PS, aggregation-induced emission (AIE) effect groups have been introduced to generate NIR AIE photosensitizers. However, currently reported NIR AIE photosensitizers all take “always-on” activity that may cause systemic phototoxic side effects. Tumor microenvironment activatable NIR AIE photosensitizers have not been reported. Here we develop an activatable NIR AIE PS nanoparticle (a-NA-PSNP) for near-infrared-II (NIR-II) fluorescence (FL) imaging-guided PDT under 808 nm excitation. NIR AIE photosensitizer (N-PS) is designed and frames with cysteine (Cys)/glutathione (GSH) responsive charge transfer complex (CTC) in bovine serum albumin (BSA) to obtain a-NA-PSNP. With the aggregated state in BSA, N-PS shows high quantum yield with good photostability. As an energy acceptor, CTC quenchs NIR-II fluorescence and ROS production capability of a-NA-PSNP in normal cells and tissues. CTC is decomposed in response to tumor microenvironment Cys/GSH, therefore recovers NIR-II fluorescence of a-NA-PSNP and efficiently generates ROS under 808 nm light irradiation. The depletion of Cys/GSH also regulates tumor intracellular reductive environment to further facilitate PDT. Both in vitro and in vivo results confirmed the tumor microenvironment selective and efficient activation of a-NA-PSNP, indicating its potential in cancer therapy.

Alkyl chain length-regulated in situ intelligent nano-assemblies with AIE-active photosensitizers for photodynamic cancer therapy

Photodynamic therapy (PDT) brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing; however, the low bioavailability of traditional photosensitizers and their dependence on oxygen severely limits their application. Aggregation-induced emission (AIE) photosensitizers (PSs) can dramatically facilitate the photosensitization effect, which can have positive impacts on tumor PDT. To-date, most AIE photosensitizers lack tumor targeting capability and possess poor cell delivery, resulting in their use in large quantities that are harmful to healthy tissues. In this study, a series of AIE photosensitizers based on pyridinium-substituted triphenylamine salts (abbreviated to TTPAs 1–6) with different alkyl chain lengths are synthesized. Results reveal that TTPAs 1–6 promote the generation of type I and type II reactive oxygen species (ROS), including ·OH and 1O2. In particular, the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains. Additionally, they can assemble with albumin, thereby forming nanoparticles (TTPA 4–6 NPs) in situ in blood, which significantly facilitates mitochondrial-targeting and strong ROS generation ability. Moreover, the TTPA 4–6 nanoparticles are pH-responsive, allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect. Therefore, the in vivo distributions of TTPA 4–6 nanoparticles are visually enriched in tumor sites and exhibited excellent photodynamic cancer therapy efficacy. This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.

AIE-active photosensitizers for concomitant fluorescence visualization and efficient photodynamic elimination of multidrug-resistant bacteria

Multidrug resistance (MDR) bacterial infection is a serious hazard to human health. Photodynamic therapy (PDT) has been deployed as an emerging tactic to combat pathogenic bacteria, but the development of efficient photosensitizers against MDR bacteria still remains a global challenge. Herein, two near-infrared (NIR) photosensitizers, named TPA-Th and TPA-Ph, which feature aggregation-induced emission (AIE), were constructed and successfully employed for MDR bacteria monitoring and effective elimination. TPA-Th and TPA-Ph exhibited great affinity with MDR G(+) and G(−) bacteria via the electrostatic interaction between the cationic pyridinium segment and the negative bacterial envelope together with hydrophobic forces. Meanwhile, the reinforced D-A effect of the two cationic AIEgens further accelerated the intersystem crossing (ISC) process and enhanced the intramolecular charge transfer (ICT), resulting in the boosted ROS generation capability particularly in the case of predominant hydroxyl radicals. Therefore, superb photodynamic antibacterial performances were achieved for both MRSA and MDR E.coli with a low dose of the AIE photosensitizers. This study provides guidance for the development of high-performance AIE-active PSs with no antibiotic resistance to defeat MDR bacterial infections.

Design of near-infrared aggregation-induced emission photosensitizers by π-bridge engineering for boosting theranostic efficacy

Design of near-infrared aggregation-induced emission photosensitizers by π-bridge engineering for boosting theranostic efficacy

Glutathione-responsive Aggregation-induced Emission Photosensitizers for Enhanced Photodynamic Therapy of Lung Cancer.

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.

A structure-guided strategy to design Golgi apparatus-targeted type-I/II aggregation-induced emission photosensitizers for efficient photodynamic therapy

The Golgi apparatus (GA) is a vital target for anticancer therapy due to its sensitivity against reactive oxygen species (ROS)-induced oxidative stress that could lead to cell death. In this study, we designed a series of aggregation-induced emission (AIE)-based photosensitizers (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) carrying different ROS with selective GA-targeted ability. The in vitro study showed that TPAPyTZ and TPAPyTC displayed strong AIE characteristics, robust type-I/II ROS production capabilities, specific GA-targeted, high photostability, and high imaging quality. The cell-uptake of TPAPyTZ was found primarily through an energy-dependent caveolae/raft-mediated endocytosis pathway. Remarkably, TPAPyTZ induced GA-oxidative stress, leading to GA fragmentation, downregulation of GM130 expression, and activation of mitochondria caspase-related apoptosis during photodynamic therapy (PDT). In vivo experiments revealed that TPAPyTZ significantly inhibited tumor proliferation under lower-intensity white light irradiation with minimal side effects. Overall, our work presents a promising strategy for designing AIEgens for fluorescence imaging-guided PDT. Additionally, it enriched the collection of GA-targeted leads for the development of cancer theranostics capable of visualizing dynamic changes in the GA during cancer cell apoptosis, which could potentially enable early diagnosis applications in the future. Statement of significanceAIE luminogens (AIEgens) are potent phototheranostic agents that can exhibit strong fluorescence emission and enhance ROS production in the aggregate states. In this study, through the precise design of photosensitizers with four different electron-acceptors, we constructed a series of potent AIEgens (TPAPyTZ, TPAPyTC, TPAPyTM, and TPAPyTI) with strong fluorescence intensity and ROS generation capacity. Among them, TPAPyTZ with an extended π-conjugation displayed the strongest ROS generation ability and anti-tumor activity, resulting in an 88 % reduction in tumor weight. Our studies revealed that the enhanced activity of TPAPyTZ may be due to its unique Golgi apparatus (GA)-targeted ability, which causes GA oxidative stress followed by effective cancer cell apoptosis. This unique GA-targeted feature of TPAPyTZ remains rare in the reported AIEgens, which mainly target organelles such as lysosome, mitochondria, and cell membrane. The successful design of a GA-targeted and potent AIEgen could enrich the collection of GA-targeted luminogens, providing a lead theranostic for the further development of fluorescence imaging-guided PDT, and serving as a tool to explore the potential mechanism and discover new GA-specific drug targets.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

Recent advances in biomimetic aggregation‐induced emission photosensitizers for photodynamic therapy and immunotherapy

AbstractThe development of novel photosensitizers (PSs) with aggregation‐induced emission (AIE) properties has emerged as a crucial advancement in the field of photodynamic therapy (PDT). However, the versatile applications of AIE PSs are limited by low encapsulation efficiency and inadequate target tissue permeability. Biomimetic technology stands out as a promising strategy to overcome these challenges, aiming to enhance AIE PSs tumor penetration efficacy, and their association with antitumor immune responses. In this review, recent advancements in biomimetic AIE PSs for PDT and immunotherapy are summarized. We start with introducing strategies involving biomimetic AIE PSs based on cell membranes and extracellular vesicles for the combined application of PDT and immunotherapy. We then discuss the preparation of biomimetic AIE PSs nanoparticles. Finally, we briefly outline the challenges and prospects associated with biomimetic AIE PSs.

Photodynamic effect of indocyanine green and its application to hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC) stands as the primary cause of liver cancers, with limited treatment options outside of surgical resection or transplant. Photodynamic therapy (PDT) using indocyanine green (ICG) as a photosensitizer offers a promising therapeutic option for HCC. ICG PDT has demonstrated efficacy in vitro and in vivo , providing a safe treatment option for patients ineligible for resection or transplant. Challenges in PDT optimization include limited light delivery, poor photosensitizer optimization, and low oxygen generation. Innovative solutions, such as ICG incorporation into nanostructures and direct administration for HCC cases, show promise. Combining ICG PDT with Lentinula edodes mycelia (LEM) and hydrogen gas inhalation may address oxygen production limitations. Utilizing a combination of therapeutic approaches and therapies may increase the efficacy of ICG PDT, making it the safer and more effective treatment option for patients. ICG’s proven clinical safety may expedite potential approval for its use in PDT. Advancements in photosensitizer technology, such as aggregation-induced emission photosensitizers (AIE-PSs), and combination therapies will enhance PDT efficacy shortly, as developments show promise for improved outcomes. For HCC patients, ICG PDT presents a valuable therapeutic option. This work is novel because it explores new combination therapy approaches, leveraging the benefits of PDT with ICG and the developments in photosensitizer technology, nanotechnology, and the combination of other treatments such as LEM and hydrogen gas, which could potentially revolutionize the treatment of HCC and offer a better prognosis for patients.

Bacterial-mediated FRET between AIE and ACQ photosensitizers for enhanced antimicrobial photodynamic therapy

Antimicrobial photodynamic therapy (aPDT) effectively treats multidrug-resistant bacterial infections by utilizing photosensitizers to generate cytotoxic reactive oxygen species. Exploiting fluorescence resonance energy transfer (FRET) effect shows great potential for enhancing the efficacy of aPDT. Typically, this method involves encapsulating fluorescent molecules, including photosensitizers, into nanomaterials or coadsorbing them onto materials. Here, we develop a strategy that directly utilizes bacteria as carriers to bring two types of photosensitizers together to induce the FRET. We designed an aggregation-induced emission (AIE) photosensitizer (CPVBP3) and an aggregation-caused quenching (ACQ) photosensitizer (TPP3), both featuring the same bacterial membrane-targeting group to direct them to bacteria. Under white light exposure (12 J/cm2), the bactericidal effect of the combination of CPVBP3 and TPP3 at 5 µM each on Escherichia coli (4.7 log10) was much stronger than their individual use at 5 or 10 µM, highlighting synergistic antibacterial action. In Escherichia coli, TPP3 absorbed the fluorescence of CPVBP3, reducing its lifetime from 0.98 ns to 0.74 ns, confirming the occurrence of FRET. This combination also demonstrated a significantly stronger synergistic aPDT effect on Acinetobacter baumannii. Moreover, CPVBP3 synergized with methylene blue against Escherichia coli, indicating the universality of this strategy. Additionally, the efficacy and biosafety of this therapeutic approach were validated in a mouse wound model infected with Escherichia coli. In summary, this FRET strategy overcomes the limitations associated with the need for pre-binding photosensitizers with materials and the challenge of these mixtures penetrating bacteria (for greater damage), ultimately opening new avenues for further enhancing the efficacy of aPDT.

One Stone, Two Birds: High-Brightness Aggregation-Induced Emission Photosensitizers for Super-Resolution Imaging and Photodynamic Therapy.

Most aggregation-induced emission (AIE) luminogens exhibit high brightness, excellent photostability, and good biocompatibility, but these AIE-active agents, which kill two birds with one stone to result in applications in both stimulated emission depletion (STED) super-resolution imaging and photodynamic therapy (PDT), have not been reported yet but are urgently needed. To meet the requirements of STED nanoscopy and PDT, D-A-π-A-D type DTPABT-HP is designed by tuning conjugated π spacers. It exhibits red-shifted emission, high PLQY of 32.04%, and impressive 1O2 generation (9.24 fold compared to RB) in nanoparticles (NPs). Then, DTPABT-HP NPs are applied in cell imaging via STED nanoscopy, especially visualizing the dynamic changes of lysosomes in the PDT process at ultrahigh resolution. After that, in vivo PDT was also conducted by DTPABT-HP NPs, resulting in significantly inhibited tumor growth, with an inhibition rate of 86%. The work here is beneficial to the design of multifunctional agents and the deep understanding of their phototheranostic mechanism in biological research.

Mitochondria-Associated Transcriptome Profiling via Localizable Aggregation-Induced Emission Photosensitizers in Live Cells.

In recent decades, there has been increasing interest in studying mitochondria through transcriptomic research. Various exogenous fusion protein-based proximity labeling methods have been reported that focus on the site of one particular protein/peptide and might also influence the corresponding localization or interactome. To enable unbiased and high spatial-resolution profiling of mitochondria-associated transcriptomes in live cells, a flexible RNA proximity labeling approach was developed using aggregation-induced emission (AIE) type photosensitizers (PSs) that possess great mitochondria-targeting capabilities. Their accumulation in an enclosed mitochondrial environment tends to enhance the fluorescence emission and reactive oxygen species generation. By comparing the in vitro optical properties, photosensitization processes, as well as the in cellulo mitochondrial specificity and RNA labeling performance of four AIE PSs, high-throughput sequencing analysis was conducted using TFPy-mediated RNA proximity labeling in live HeLa cells. This approach successfully captured a comprehensive list of transcripts, including mitochondria-encoded RNAs, as well as some nuclear-derived RNAs located at the outer mitochondrial membrane and interacting organelles. This small molecule-based proximity labeling method bypasses complex genetic manipulation and transfection steps, making it readily applicable for diverse research purposes.

DNA‐Programmed (De)Hybridization of Near‐Infrared Photosensitized UCNP‐QDs‐GNPs Nanoprobes for MicroRNA Imaging and Image‐Guided Cancer Therapy

AbstractAccurate and sensitive analysis of cancer‐associated microRNAs in living tissue is of great significance for the early diagnosis and treatment of cancer. Herein, a hierarchical nanoprobe denoted as UCNP‐QDs‐GNPs is delicately designed, where a near‐infrared (NIR) absorptive upconversion nanoparticle (UCNP) serves as the core, broad‐absorptive and bright emissive quantum dots (QDs) and emission‐quencher gold nanoparticles (GNPs) surround as satellites for microRNA imaging and image‐guided cancer therapy. Through the programmed assembly of heterobivalent DNA‐conjugated QDs with DNA‐modified GNPs and UCNPs, the well‐defined nanostructured UCNP‐QDs‐GNPs are generated with quenched fluorescence. Upon encountering the microRNA‐21 target, GNPs underwent catalytic disassembly, resulting in the concurrent recovery and amplification of fluorescence from QDs and UCNPs, which enabled sensitive imaging and quantification of microRNA‐21 within living cells. Furthermore, dithiol‐constituted aggregation‐induced emission (AIE) photosensitizers bonded on the surface of QDs, are effectively photosensitized by the QDs. The NIR excitation harvested by UCNPs is therefore efficiently transferred to QDs and subsequently converged on the AIE photosensitizers, boosting photodynamic activity for image‐guided therapy in deep‐seated tumors. The DNA‐programmed (de)hybridization strategy, facilitating the conversion of NIR excitation into imaging signals and photodynamic activity, offers a promising avenue for the early theranostics of malignancies.

Recyclable and Environmentally Friendly Magnetic Nanoparticles with Aggregation-Induced Emission Photosensitizer for Sustainable Bacterial Inactivation in Water.

Bacterial photodynamic inactivation based on the combined actions of photosensitizers, light, and oxygen presents a promising alternative for eliminating bacteria compared to conventional water disinfection methods. However, a significant challenge in this approach is the inability to retrieve photosensitizers after phototreatment, posing potential adverse environmental impacts. Additionally, conventional photosensitizers often exhibit limited photostability and photodynamic efficiency. This study addresses these challenges by employing an aggregation-induced emission (AIE) photosensitizer, iron oxide magnetic nanoparticles (Fe3O4 MNPs), and Pluronic F127 to fabricate AIE magnetic nanoparticles (AIE MNPs). AIE MNPs not only exhibit fluorescence imaging capabilities and superior photosensitizing ability but also demonstrate broad-spectrum bactericidal activities against both Gram-positive and Gram-negative bacteria. The controlled release of TPA-Py-PhMe and magnetic characteristics of the AIE MNPs facilitate reuse and recycling for multiple cycles of bacterial inactivation in water. Our findings contribute valuable insights into developing environmentally friendly disinfectants, emphasizing the full potential of AIE photosensitizers in photodynamic inactivation beyond biomedical applications.

Targeted antibacterial photodynamic therapy with aggregation‐induced emission photosensitizers

AbstractWith the increasing prevalence of infectious diseases caused by drug‐resistant bacteria, there is an urgent need to develop innovative therapies alternative to antibiotics. Among these alternatives, the aggregation‐induced emission (AIE) photosensitizers (PSs) stand out with their integrated imaging and therapeutic functionalities, allowing for early monitoring and image‐guided ablation of bacteria. AIE fluorescent probes with unique optical properties excel in selective bacterial imaging. Furthermore, AIE‐enabled reactive oxygen species (ROS)‐mediated antibacterial photodynamic therapy can operate on multiple targets to oxidize bacteria. Also, as they are able to specifically target bacteria, AIE PSs can ameliorate the limitations of the small‐scale action of ROS. This review methodically discusses the different strategies that can be employed using AIE PSs for targeting bacteria, including sheltered bacteria. The challenges and future opportunities of using AIE PSs in this emerging field are also briefly discussed.

Study of transient absorption spectroscopy of a D-π-A structure aggregation-induced emission luminogen and its photodynamic therapy application.

Photodynamic therapy (PDT) represents an emerging and noninvasive modality that has gained clinical approval for the treatment of cancers, leveraging photosensitizers for optimal therapeutic efficacy. In this study, we synthesized a photosensitizer (denoted as DTCSPP) exhibiting a donor-π-acceptor (D-π-A) structural motif. The DTCSPP manifests aggregation-induced emission (AIE) characteristics, along with good biocompatibility and mitochondrial targeting capabilities attributed to its intrinsic charge and D-π-A architecture. The excited-state intramolecular charge transfer of DTCSPP was systematically investigated in both solution and aggregate states using femtosecond transient absorption spectroscopy (fs-TA). The fs-TA results revealed that DTCSPP exhibited a more rapid and facile excited-state molecular motion in the solution state compared to the aggregate state, implying the predominance of nonradiative decay in its photophysical processes within the solution. Given its ability to simultaneously generate type I and type II reactive oxygen species and induce ferroptosis and autophagy in cancer cells, DTCSPP demonstrates effectiveness in PDT at both cellular and in vivo levels. This study contributes a comprehensive understanding of the excited-state intramolecular charge transfer dynamics of charged D-π-A type AIE photosensitizers, shedding light on their potential application in PDT. The multifaceted capabilities of DTCSPP underscore its promise in advancing the field of anticancer therapeutics, providing valuable insights for the identification of anticancer targets and the development of novel drugs.

Construction of Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy via Photoinduced Electron Transfer Mechanism

Construction of Type I Aggregation-Induced Emission Photosensitizers for Photodynamic Therapy via Photoinduced Electron Transfer Mechanism

Reviewing the evolutive ACQ-to-AIE transformation of photosensitizers for phototheranostics.

Photodynamic therapy (PDT) represents an emerging noninvasive treatment technique for cancers and various nonmalignant diseases, including infections. During the process of PDT, the physical and chemical properties of photosensitizers (PSs) critically determine the effectiveness of PDT. Traditional PSs have made great progress in clinical applications. One of the challenges is that traditional PSs suffer from aggregation-caused quenching (ACQ) due to their discotic structures. Recently, aggregation-induced emission PSs (AIE-PSs) with a twisted propeller-shaped conformation have been widely concerned because of high reactive oxygen species (ROS) generation efficiency, strong fluorescence efficiency, and resistance to photobleaching. However, AIE-PSs also have some disadvantages, such as short absorption wavelengths and insufficient molar absorption coefficient. When the advantages and disadvantages of AIE-PSs and ACQ-PSs are complementary, combining ACQ-PSs and AIE-PSs is a "win-to-win" strategy. As far as we know, the conversion of traditional representative ACQ-PSs to AIE-PSs for phototheranostics has not been reviewed. In the review, we summarize the recent progress on the ACQ-to-AIE transformation of PSs and the strategies to achieve desirable theranostic applications. The review would be helpful to design more efficient ACQ-AIE-PSs in the future and to accelerate the development and clinical application of PDT.