Aggregation-induced Emission Photosensitizers Research Articles

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.

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.

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.

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.

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.

Endoplasmic Reticulum-Targeting AIE Photosensitizers to Boost Immunogenic Cell Death for Immunotherapy of Bladder Carcinoma.

Bladder cancer is characterized by high rates of recurrence and multifocality. Immunogenic cell death (ICD) of cancer cells has emerged as a promising strategy to improve the immunogenicity of tumor cells for enhanced cancer immunotherapy. Although photosensitizer-based photodynamic therapy (PDT) has been validated as capable of inducing ICD in cancer cells, the photosensitizers with a sufficient ICD induction ability are still rare, and there have been few reports on the development of advanced photosensitizers to strongly evoke the ICD of bladder cancer cells for eliciting potent antitumor immune responses and eradicating bladder carcinoma in situ. In this work, we have synthesized a new kind of endoplasmic reticulum (ER)-targeting aggregation-induced emission (AIE) photosensitizer (named DPASCP-Tos), which could effectively anchor to the cellular ER and trigger focused reactive oxygen species (ROS) production within the ER, thereby boosting ICD in bladder cancer cells. Furthermore, we have demonstrated that bladder cancer cells killed by ER-targeted PDT could serve as a therapeutic cancer vaccine to elicit a strong antitumor immunity. Prophylactic vaccination of the bladder cancer cells killed by DPASCP-Tos under light irradiation promoted the maturation of dendritic cells (DCs) and the expansion of tumor antigen-specific CD8+ T cells in vivo and protected mice from subsequent in situ bladder tumor rechallenge and extended animal survival. In summary, the ER-targeted AIEgens developed here significantly amplified the ICD of bladder cells through focused ROS-based ER oxidative stress and transformed bladder cancer cells into the therapeutic vaccine to enhance immunogenicity against orthotopic bladder cancer, providing valuable insights for bladder carcinoma treatment.

Rational Design of AIE Photosensitizers with Full‐Visible Color Emission and Efficient ROS Generation

AbstractOrganic photosensitizers (PSs) with aggregation‐induced emission (AIE) characteristics have shown several advantages in photodynamic therapy (PDT). However, how to design PSs with the required optical and biological properties is a formidable challenge. In this work, a series of AIE active pyridine‐ and pyridinium‐functionalized carbazole with different substituents are designed and synthesized. Compared to other analogs, BK‐Pys‐BP containing benzophenone moiety on the pyridinium unit produces reactive oxygen species (ROS) efficiently in the presence of light due to its large spin‐orbit coupling constant to promote efficient intersystem crossing. Based on its structure, three molecules with enhanced donor–acceptor strength and conjugation are further investigated to realize emission covering the whole visible region. The cationic nature and excellent ROS generation ability of benzophenone‐containing AIE photosensitizers allows for specific imaging of mitochondria, killing cancer cells, and as a singlet oxygen donor to catalyze the formation of endoperoxides. Thus, the present work presents an effective strategy for creating AIE photosensitizers with efficient ROS generation for wide biological applications.

Integrating Anion-π+ Interaction and Crowded Conformation to Develop Multifunctional NIR AIEgen for Effective Tumor Theranostics via Hippo-YAP Pathway.

The technology of aggregation-induced emission (AIE) presents a promising avenue for fluorescence imaging-guided photodynamic cancer therapy. However, existing near-infrared AIE photosensitizers (PSs) frequently encounter limitations, including tedious synthesis, poor tumor retention, and a limited understanding of the underlying molecular biology mechanism. Herein, an effective molecular design paradigm of anion-π+ interaction combined with the inherently crowded conformation that could enhance fluorescence efficacy and reactive oxygen species generation was proposed through a concise synthetic method. Mechanistically, upon photosensitization, the Hippo signaling pathway contributes to the death of melanoma cells and promotes the nuclear location of its downstream factor, yes-associated protein, which regulates the transcription and expression of apoptosis-related genes. The finding in this study would trigger the development of high-performance and versatile AIE PSs for precision cancer therapy based on a definite regulatory mechanism.

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.

D‐type neuropeptide decorated AIEgen/RENP hybrid nanoprobes with light‐driven ROS generation ability for NIR‐II fluorescence imaging‐guided through‐skull photodynamic therapy of gliomas

AbstractGlioma is one of the most common malignant tumors of the central nervous system, leading high mortality rates in human. Aggregation‐induced emission (AIE) photosensitizers‐based photodynamic therapy (PDT) has emerged as a promising therapeutic strategy for least‐invasive treatment of glioma, which involves local irradiation of the tumor using an external near‐infrared (NIR) laser. Unfortunately, most AIE photosensitizers suffered from poorly penetration of the visible light excitation, bad spatiotemporal resolution in deep tissues and low efficient blood‐brain barrier (BBB) crossing ability, which greatly limited the clinical practice of AIE photosensitizers for especially deep‐seated brain tumor treatment. In this work, we developed a multifunctional NIR‐driven theranostic agent through hybrid of AIE photosensitizers TIND with rare‐earth doping nanoparticles (RENPs) NaGdF4:Nd/Yb/Tm with up/down dual‐mode conversion luminescence. The theranostic agent was further decorated with D‐type neuropeptide DNPY for crossing BBB and targeting glioma. Under the 808‐nm light irradiation, the down‐conversion NIR‐II luminescence could indicate the position glioma and the upconversion NIR‐I luminescence could trigger the AIE photosensitizers producing reactive oxygen species to inhibit orthotopic glioma tumor growth in situ. These results demonstrate that the integration of D‐type neuropeptide, AIE photosensitizers and RENPs could be promising candidates for in vivo NIR‐II fluorescence image‐guided through‐skull PDT treatments of brain tumors.

Construction of aggregation-induced emission photosensitizers through host-guest interactions for photooxidation reaction and light-harvesting

In the present work, we have designed and synthesized a triphenylamine modified cyanophenylenevinylene derivative (TPCI), which can self-assembly with cucurbit[6]uril (CB[6]) and cucurbit[8]uril (CB[8]) through host-guest interactions to form supramolecular complexes (TPCI-CB[6]) and supramolecular polymers (TPCI-CB[8]) in the aqueous solution. The supramolecular assemblies of TPCI-CB[6] and TPCI-CB[8] not only exhibited high singlet oxygen (1O2) production efficiency as photosensitizers, but also realized the application in the construction of artificial light-harvesting systems due to the excellent fluorescence properties in the aqueous solution. The production efficiency of 1O2 has been effectively improved after the addition of CB[6] and CB[8] for TPCI, which were applied as efficient photosensitizers in the photooxidation reactions of thioanisole and its derivatives with the highest yield of 98% in the aqueous solution. The excellent fluorescence properties of TPCI-CB[6] and TPCI-CB[8] can be used as energy donors in artificial light-harvesting systems with energy acceptors sulforhodamine 101 (SR101) and cyanine dye 5 (Cy5), in which one-step energy transfer processes of TPCI-CB[6]+SR101 and TPCI-CB[8]+Cy5, and a two-step sequential energy transfer process of TPCI-CB[6]+SR101+Cy5 were constructed to simulate the natural photosynthesis system.

From cell membrane to mitochondria: Time-dependent AIE photosensitizer for fluorescence imaging and photodynamic anticancer therapy

Aggregation-induced emission photosensitizers (AIE-PSs) targeting different subcellular organelles with time-dependent manner are highly promising for clinical applications but rarely reported. Herein, we designed and synthesized the near-infrared (NIR) emission AIE-PS (CTQ-S) with broad absorption and excellent type I reactive oxygen species (ROS) generation efficiency that was superior to the widely used PS (Rose Bengal and Chlorine 6). With short-term incubation, CTQ-S anchored on the cell membrane (Rr: 0.843, Rr is for Pearson correlation coefficient) and gradually entered the mitochondria (Rr: 0.937) of cancer cells, showing excellent time-dependent fluorescence fluorescent imaging effect. Furthermore, CTQ-S realized the selective photodynamic therapy (PDT) effect in a time-dependent manner under white light irradiation. This work provided a new way for cancer cells fluorescence imaging and PDT.

Development of Sulfonamide‐Functionalized Charge‐Reversal AIE Photosensitizers for Precise Photodynamic Therapy in the Acidic Tumor Microenvironment

AbstractTumor‐targeted photodynamic therapy (PDT) is desirable as it can achieve efficient killing of tumor cells with no or less harm to normal cells. Herein, a facile molecular engineering strategy is developed for photosensitizers (PSs) with aggregation induced emission (AIE) characteristics and responsive properties to the acidic tumor microenvironment (TME). By the marriage of pH‐sensitive sulfonamide moieties with AIE PSs, two near‐infrared AIE luminogens called DBP‐SPy and DBP‐SPh are designed and synthesized. Both luminogens can form negatively charged nanoaggregates in the aqueous medium at physiological pH. The DBP‐SPy nanoaggregates undergo surface charge conversion to become positive at pH close to the signature pH of TME, while DBP‐SPh nanoaggregates show no such property. The endowed response to acidic TME enables the enhanced cellular uptake of DBP‐SPy at pH = 6.8. By contrast, its cellular uptake is much sacrificed at pH 7.4. As a result, under white light irradiation, DBP‐SPy nanoaggregates demonstrate a considerable photodynamic therapeutic effect on cancer cells in vitro and excellent tumor growth inhibition in vivo. Hence, this study not only provides an acidic TME‐responsive AIE PS for precise PDT, but also inspires new design strategies for AIE‐based theragnostic systems with targeting characteristics.