Aggregation-induced Emission Photosensitizer Research Articles

Aggregation-induced emission of TTCPy-3: A novel approach for eradicating Nocardia seriolae infections in aquatic fishes

Aquatic fishes are threatened by the strong pathogenic bacterium Nocardia seriolae, which challenges the current prevention and treatment approaches. This study introduces luminogens with aggregation-induced emission (AIE) as an innovative and non-antibiotic therapy for N. seriolae. Specifically, the AIE photosensitizer, TTCPy-3 is employed against N. seriolae. We evaluated the antibacterial activity of TTCPy-3 and investigated the killing mechanism against N. seriolae, emphasizing its ability to aggregate within the bacterium and produce reactive oxygen species (ROS). TTCPy-3 could effectively aggregate in N. seriolae, generate ROS, and perform real-time imaging of the bacteria. A bactericidal efficiency of 100% was observed while concentrations exceeding 4 μM in the presence of white light irradiation for 10 min. In vivo, evaluation on zebrafish (Danio rerio) confirmed the superior therapeutic efficacy induced by TTCPy-3 to fight against N. seriolae infections. TTCPy-3 offers a promising strategy for treating nocardiosis of fish, paving the way for alternative treatments beyond traditional antibiotics and potentially addressing antibiotic resistance.

An AIEgen and Iodine Double-Ornamented Platinum(II) Complex for Bimodal Imaging-Guided Chemo-Photodynamic Combination Therapy.

Real-time biodistribution monitoring and enhancing the therapeutic efficacy of platinum(II)-based anticancer drugs are urgently required to elevate their clinical performance. Herein, a tetraphenylethene derivative (TP) with aggregation-induced emission (AIE) properties and an iodine atom are selected as ligands to endow platinum (II) complex TP-Pt-I with real-time in vivo self-tracking ability by fluorescence (FL) and computerized tomography (CT) imaging, and improved anticancer efficacy by the combination of chemotherapy and photodynamic therapy. Especially, benefiting from the formation of a donor-acceptor-donor structure between the AIE photosensitizer TP and Pt-I moiety, the heavy atom effects of Pt and I, and the presence of I, TP-Pt-I displayed red-shifted absorption and emission wavelengths, enhanced ROS generation efficiency, and improved CT imaging capacity compared with the pristine TP and the control agent TP-Pt-Cl. As a result, the enhanced intratumoral accumulation of TP-Pt-I loaded nanoparticles is readily revealed by dual-modal FL and CT imaging with high contrast. Meanwhile, the TP-Pt-I nanoparticles show significantly improved tumor growth-inhibiting effects on an MCF-7 xenograft murine model by combining the chemotherapeutic effects of platinum(II) and the photodynamic effects of TP. This self-tracking therapeutic complex thus provides a new strategy for improving the therapeutic outcomes of platinum(II)-based anticancer drugs.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

Photodynamic inactivation of Listeria monocytogenes using a natural aggregation-induced emission photosensitizer and its application in salmon preservation

Photodynamic sterilization has been regarded as a promising alternative to conventional antibacterial approaches. However, the photodynamic efficiency of conventional photosensitizer is often compromised by aggregation-induced quenching effects. Photosensitizers, especially natural products, with aggregation-induced emission (AIE) properties open a new avenue for photodynamic sterilization. Herein, we investigated the photodynamic antibacterial performance and mechanism of the AIE-type natural product of berberine (BBR) against Listeria monocytogenes (L. monocytogenes). The bactericidal effect was assessed through the determination of minimum bactericidal concentration and implementation of anti-biofilm experiments. The results showed that BBR can significantly suppress the proliferation of L. monocytogenes and can efficiently remove the L. monocytogenes-derived biofilm in a concentration-dependent trend. The mechanism of killing L. monocytogenes has been speculated based on bacterial morphology characterization, viability staining results, enzyme activity assays, DNA electrophoresis analysis, and molecular docking. The excellent anti-bacterial activity of BBR mediated photodynamic process may account for its abilities to the irreversibly disruption of bacterial membrane, inhibition of intracellular enzyme activity and decomposition of intracellular DNA molecules. We also demonstrated that BBR embedded sodium alginate/chitosan packaging film is feasible to maintain the freshness of salmon under light illumination by inhibiting the bacterial proliferation.

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.

Aggregation-induced emission photosensitizer for antibacterial therapy of methicillin-resistant Staphylococcus aureus

A cationic aggregation-induced emission photosensitizer (AIE-PS) MNNPyBB has been reported to have antibacterial effects against both gram-positive and gram-negative bacteria. The bacterial kill mechanism has been investigated and elucidated. In...

Aggregation-induced emission photosensitizer microneedles for enhanced melanoma photodynamic therapy.

The incidence and mortality rates of skin melanoma have been increasing annually. Photodynamic therapy (PDT) enables effective destruction of tumor cells while minimizing harm to normal cells. However, traditional photosensitizers (PSs) suffer from photobleaching, photodegradation and the aggregation-caused quenching (ACQ) effect, and it is challenging for light to reach the deep layers of the skin to maximize the efficacy of PSs. Herein, we developed dissolving microneedles (MNs) loaded with PSs of TPE-EPy@CB[7] through supramolecular assembly. The PSs effectively enhanced the type-I reactive oxygen species (ROS) generation capacity, with a concentration of 2 μM possessing nearly half of the tumor cell-killing ability under 10 min white light irradiation. The MNs were successfully pierced into the targeted site for precise drug delivery. Additionally, the conical structure of the MNs, as well as the lens-like structure after dissolution, facilitated the transmission of light in the subcutaneous tissue, achieving significant inhibition of tumor growth with a tumor suppression rate of 97.8% and no systemic toxicity or side effects in melanoma mice. The results demonstrated the potent melanoma inhibition and biosafety of this treatment approach, exhibiting a new and promising strategy to conquer malignant melanoma.

Yeast Nanoparticle‐powered Tumor Photodynamic‐Immunotherapy

Photodynamic therapy (PDT) uses a combination of light and a photosensitizing agent to destroy cancerous cells. However, the PDT alone often insufficient to elicit an effective anti-tumor response due to various factors including insufficient ROS generation and the weak induced immune response. Here, we report yeast nanoparticles (YNPs) loaded with aggregation-induced emission (AIE) photosensitizer QMC12 (YNP-QMC) for enhanced photodynamic-immunotherapy in animal models. YNPs have a strong immune adjuvant effect which could significantly activate various APCs and reverse the immunosuppressive microenvironment at tumor and tumor-draining lymph nodes (TDLNs) sites. More importantly, YNP-QMC can be attached with tumor cell antigens released from dying cells after PDT. This antigen attached nanoparticle can efficiently migrate to tumor-draining lymph nodes and activate an antigen-specific systemic antitumor immunity. In combination with anti-PD-L1, this strategy could promote the elimination of primary tumors and inhibit the growth of distant tumors. Thus, our AIE photosensitizer and adjuvant YNP-powered PDT strategy provides a simple way to enhance efficacy of PDT.

COX-2 inhibition mediated aggregation-induced emission photosensitizer target the Golgi apparatus for selective imaging of cancer cells and enhanced photodynamic therapy

Photodynamic therapy (PDT) exerts its therapeutic effects by inducing apoptosis, necrosis, and microvascular damage in tumor cells, but it also causes inflammation and induces the expression of angiogenic factors, accelerating tumor metastasis and proliferation. In this study, aggregation-induced emission (AIE) photosensitizer (PS) for PDT was combined with the cyclooxygenase-2 (COX-2) inhibitor indomethacin (IMC) for cancer-selective imaging and more efficiency in inducing apoptosis in cancer cells. In detail, inhibition of COX-2-mediated AIE PS effectively targeted the Golgi apparatus (GA) of cancer cells to generate large amounts of reactive oxygen species (ROS) in situ, thereby exerting a PDT effect. Specifically, COX-2 and other key enzymes that trigger inflammation and metastasis were significantly inhibited. It had more potent anti-tumor activity (tumor inhibition rate of 64.32 %), as well as anti-metastatic and anti-proliferative effects compared to the use of usual AIE PS.

A near-infrared aggregation-induced emission photosensitizer targeting mitochondria for depleting Cu2+ to trigger light-activated cancer cells oncosis

Abnormally high levels of copper in tumors stimulate malignant proliferation and migration of cancer cells, which proposes a formidable challenge for the thorough therapy of malignant tumors. In this work, we developed a reliable, mitochondria-targeted near-infrared aggregation-induced emission fluorescent probe, TTQ-Th, whose thiourea moiety specifically could recognize mitochondria even both upon loss of mitochondrial membrane potential or in fixated cells, and can capture copper overexpressed by tumor cells, leading to severe copper deficiency. In parallel, TTQ-Th can generate sufficient reactive oxygen species (ROS) upon photoexcitation, while copper deficiency inhibits expression of related copper-based enzymes, resulting in a decline in ATP production. Such energy deficiency, combined with reduced MMP and elevated oxidative stress can lead to critical cell oncosis. Both in vitro and intracellular experiments can illustrate that the elevated ROS has remarkable damage to tumor cells and contributes to the elimination of the primary tumor, while copper deficiency further hinder tumor cell migration and induces G0/G1 cell cycle arrest in a dose-dependent manner, which is an efficacious strategy for the treatment of malignant tumors.

Engineered Extracellular Vesicles Expressing Siglec-10 Camouflaged AIE Photosensitizer to Reprogram Macrophages to Active M1 Phenotype and Present Tumor-Associated Antigens for Photodynamic Immunotherapy.

Cancer immunotherapy has attracted considerable attention due to its advantages of persistence, targeting, and ability to kill tumor cells. However, the efficacy of tumor immunotherapy in practical applications is limited by tumor heterogeneity and complex tumor immunosuppressive microenvironments in which abundant of M2 macrophages and immune checkpoints (ICs) are present. Herein, two type-I aggregation-induced emission (AIE)-active photosensitizers with various reactive oxygen species (ROS)-generating efficiencies are designed and synthesized. Engineered extracellular vesicles (EVs) that express ICs Siglec-10 are first obtained from 4T1 tumor cells. The engineered EVs are then fused with the AIE photosensitizer-loaded lipidic nanosystem to form SEx@Fc-NPs. The ROS generated by the inner type-I AIE photosensitizer of the SEx@Fc-NPs through photodynamic therapy (PDT) can convert M2 macrophages into M1 macrophages to improve tumor immunosuppressive microenvironment. The outer EV-antigens that carry 4T1 tumor-associated antigens directly stimulate dendritic cells maturation to activate different types of tumor-specific T cells in overcoming tumor heterogeneity. In addition, blocking Siglec-10 reversed macrophage exhaustion for enhanced antitumor ability. This study presents that a combination of PDT, immune checkpoints, and EV-antigens can greatly improve the efficiency of tumor immunotherapy and is expected to serve as an emerging strategy to improve tumor immunosuppressive microenvironment and overcome immune escape.

Macrophage Membrane-Camouflaged Aggregation-Induced EmissionNanoparticles Enhance Photodynamic-Immunotherapy to Delay Postoperative Tumor Recurrence.

Surgery is a traditional tumor treatment, and immunotherapy can reduce the postoperative recurrence of tumors. However, the intrinsic limits of low responsive rate and non-tumor specificity of immunotherapy agents are still insufficient to address therapeutic demands. Herein, the macrophages membrane camouflaged nanoparticles (NPs), named M@PFC, consisting of the aggregation-induced emission photosensitizer (PF3-PPh3 ) and immune adjuvant (CpG), are reported. As the protein on the membrane interacts with the vascular cell adhesion molecule 1 (VCAM-1) of cancer cells, M@PFC efficiently transports CpG to the tumor. Meanwhile, M@PFC can evade clearance by the immune system and prolong the circulation time in vivo; thus, enhancing their accumulation in tumors. PF3-PPh3 promotes high production of reactive oxygen species (ROS) and triggers immune cell death (ICD) in tumor cells under light exposure. Importantly, CpG enrichment in tumors can stimulate tumor cells to produce immune factors to assist in enhancing ICD effects. The synergistic effect combining the PDT properties of the aggregation-induced emission (AIE)-active photosensitizer and immunotherapy properties of CpG significantly delays tumor recurrence after surgery. In conclusion, this strategy achieves the synergistic activation of the immune system for anti-tumor activity, providing a novel paradigm for the development of therapeutic nanodrugs to delay postoperative tumor recurrence.

Biotin receptor and mitochondria dual targeted AIE photosensitizer for fluorescence imaging guided photodynamic anticancer therapy

Rational design of organelle targeted therapeutic platform in where the drug can be targeted to destroy tumor cells as much as possible, is one of the effective ways to improve the therapeutic outcomes and minimize the cytotoxicity to normal cells. Here, photosensitizer TSPy-B with aggregation-induced emission (AIE) feature, biotin receptor and mitochondria dual-targeted capability, and high reactive oxygen species (ROS) generation efficiency was designed for fluorescence imaging guided photodynamic therapy (PDT) by linking biotin group to D-π-A type AIE dyes via ester bonds. Notably, cell imaging experiments showed that TSPy-B could selectively target tumor cells with biotin receptor overexpression and further exhibit mitochondria targeting ability. The in vitro anticancer mechanism confirmed that after cell internalization, TSPy-B localized in the mitochondrial site and produced ROS resulting in mitochondrial dysfunction and cell death. ROS generation experiments showed that TSPy-B could simultaneously produce 1O2 and highly toxic free radicals which not depended on the oxygen level of solid tumor. The cell killing effect of TSPy-B was also confirmed in hypoxic culture model. In vivo photodynamic therapy experiments demonstrated that TSPy-B could effectively inhibit tumor growth and had good biological safety. This work provides a choice for development of highly targeted photosensitizers for clinical fluorescence imaging guided PDT.

Efficient type Ⅰ and type Ⅱ ROS generated aggregation-induced emission photosensitizer for mitochondria targeted photodynamic therapy

Fluorescence imaging-guided photodynamic therapy (PDT) is considered as an ideal alternative strategy to treat tumors. However, insufficient supply of oxygen in solid tumor tissue, aggregation-caused quenching (ACQ) of photosensitizers (PSs), poor targeting-specificity of cancer cells and short wavelengths of emission are representative obstacles for effective PDT. In this paper, three D-π-A structured PSs TSB-OH, TSBPy-OH, TSBPy-DNT with aggregation induced emission (AIE) properties and integrated type I and type II ROS generation were synthesized by modulating distinct acceptor units. Among them, TSBPy-OH is optimal with multiple advantages including near-infrared emission, good biocompatibility, remarkably intracellular ROS production ability, mitochondria targeting capability inducing cell apoptosis and enhancing PDT, and long-term tumor retention ability for imaging-guided photodynamic therapy. More importantly, efficient in vitro cancer cells damage, in vivo tumor ablation and ignorable damage in major organs during PDT are demonstrated, suggesting potential capability of TSBPy-OH in safe and effective fluorescence imaging-guided PDT. This successful example of AIE theranostics design would provide a reference for the modification of D-π-A structure organic AIEgens.

Platelet membrane fusion liposome loaded with type I AIE photosensitizer to induce chemoresistance cancer pyroptosis and immunogenic cell death for enhancing cancer immunotherapy

Cancer cells often develop resistance to chemotherapy induced apoptosis, and targeting non-apoptosis-related pathways is a potential anti-drug resistant tumor strategy. Here, we designed a platelet membrane fusion liposome nanovesicle system (named TFL) loaded with type I aggregation induced-emission (AIE) photosensitizer (TBP-2), which is used to promote the pyroptosis and immunogenic cell death (ICD) of chemoresistance breast cancer cells. Because of the highly expressed P-selectin protein in platelets, TFL can target the highly expressed CD44 receptor in chemoresistance breast cancer cells and deliver TBP-2 molecules to these cells. Under the irradiation of external light sources, TBP-2 achieves type-I photodynamic therapy (PDT), generating a large number of hydroxyl free radicals, inducing pyroptosis and ICD of chemoresistance cancer cells, promoting DC cell maturation and T cell infiltration. In vivo animal experiments have shown that the TFL system can promote T cell immunity, slow down distal chemoresistance tumor growth, achieve immune memory effect, and inhibit chemoresistance tumor rechallenge. Compared with high-dose chemotherapy, TFL + L has better immune stimulation and therapeutic effect on drug-resistant breast cancer. This system may become an adjuvant therapy for clinical chemotherapy in the future, further enhancing the immune response and therapy effect of drug-resistant tumors.

The Role of Structural Hydrophobicity on Cationic Amphiphilic Aggregation-Induced Emission Photosensitizer-Bacterial Interaction and Photodynamic Efficiency.

The aggregation-induced emission photosensitizer (AIE PS) has stood out as an alternative and competent candidate in bacterial theranostics, particularly with the use of cationic AIE PS in bacterial discrimination and elimination. Most reported work emphasizes the role of electrostatic interaction between cationic AIE PS and negatively charged bacterial surfaces, enabling broad applications from bacterial discrimination to bacterial killing. However, the underlying targeting mechanism and the design rationale of the cationic AIE PS for effective bacterial labeling remain poorly investigated. In this Article, we designed and synthesized a series of cationic amphiphilic AIE PSs with different calculated log P values. Then, we systemically studied the relationship between the hydrophobicity variation of AIE PS and bacterial targeting outcomes, the dose of AIE PS needed to label various species of bacteria, and their photodynamic antibacterial efficiency. The findings in this work provide a better understanding of the unclear AIE PS-bacterial interaction mechanism and some insights into the structural design strategies of cationic amphiphilic AIE PS for better development in bacterial theranostics.

Aggregation-induced emission photosensitizer/bacteria biohybrids enhance Cerenkov radiation-induced photodynamic therapy by activating anti-tumor immunity for synergistic tumor treatment

Cerenkov radiation-induced photodynamic therapy (CR-PDT) gets rid of the limited tissue penetration depth of the external light source and provides a feasible scheme for the PDT excited by the internal light. However, due to the low luminescence intensity of Cerenkov radiation, CR-PDT alone cannot effectively inhibit tumor growth, curbing the potential clinical translation of CR-PDT. Herein, we reported an AIE-PS/bacteria biohybrid (EcN@TTVP) composed of Escherichia coli Nissle 1917 (EcN) loaded with aggregation-induced emission photosensitizer (AIE-PS) termed TTVP, which enhanced CR-PDT by activating anti-tumor immunity for synergistic tumor treatment. The preferential tumor-colonized EcN@TTVP and radiopharmaceutical 18F-fluorodeoxyglucose (18F-FDG) were administered sequentially to enable them to co-enrich in the tumor site, thereby triggering CR-PDT and promoting immunogenic tumor cell death. Most importantly, EcN acting as immunoadjuvants enhanced the maturation of dendritic cells (DCs) and priming of cytotoxic T cells (CTLs). Therefore, under the synergistic treatment of CR-PDT and immunotherapy, AIE-PS/bacteria biohybrids resulted in either efficient tumor remission or a survival prolongation in tumor-bearing mice, which presented significant advantages over single CR-PDT. Remarkably, no obvious toxic effects were observed during the treatment. In this study, we proposed a synergistic therapeutic strategy based on EcN@TTVP for combined CR-PDT and immunotherapy against tumors. Moreover, this strategy may have great potential in clinical translation and provide references for deep-seated tumor treatment. Statement of significancePDT is restricted due to the shallow penetration depth of light into tumor tissues. Using CR as the excitation light source for PDT can overcome the aforementioned issue and greatly expand the application of PDT. However, the low efficacy of single CR-PDT limits further its applications. Therefore, the design and development of feasible strategies to improve the efficacy of CR-PDT are of immediate importance. Introducing probiotics to our study can be used not only as tumor-targeting carriers of photosensitizers but also as immunoadjuvants. Under co-stimulation by immunogenic tumor cell death triggered by CR-PDT and probiotics acting as immunoadjuvants, anti-tumor immune responses were effectively activated, thus remarkably enhancing the efficacy of CR-PDT.

Removal of antibiotic resistant bacteria in wastewater by aggregation-induced emission photosensitizer

The spread of antibiotic resistant bacteria from wastewater to the environment will pose serious threats to human health. It is a potential solution to prepare photosensitizers with broad-spectrum antibacterial activity for use in the photo-oxidation process to supplement the wastewater treatment system. Here, an aggregation-induced emission photosensitizer with D-π-A structure (TBTPy) has been reasonably designed and successfully developed. TBTPy can generate singlet oxygen with extraordinarily high efficiency under white-light irradiation owing to the small singlet–triplet energy gap. TBTPy has a rapid and efficient photo-oxidative killing effect on bacteria and fungi (such as MRSA, S. aureus, E. coli and C. albicans). TBTPy kills bacteria by binding to bacterial surface and releasing singlet oxygen to destroy cell membrane, leading to leakage of bacterial genetic material. This successful case can provide practical guidance for the subsequent development of AIE photosensitizers.

An Alkaline Phosphatase-Responsive Aggregation-Induced Emission Photosensitizer for Selective Imaging and Photodynamic Therapy of Cancer Cells.

Fluorescence-guided photodynamic therapy (PDT) has been considered as an emerging strategy for precise cancer treatment by making use of photosensitizers (PSs) with reactive oxygen species (ROS) generation. Some efficient PSs have been reported in recent years, but multifunctional PSs that are responsive to cancer-specific biomarkers are rarely reported. In this study, we introduced a phosphate group as a cancer-specific biomarker of alkaline phosphatase (ALP) on a PS with the features of aggregation-induced emission (AIE) for cancer cell imaging and therapy. In cancer cells with high ALP expression, the phosphate group on the AIE probe is selectively hydrolyzed by ALP. Consequently, the hydrophobic probe residue is aggregated in aqueous media and gives a "turn on" fluorescent response. Moreover, fluorescence-guided PDT was realized by the aggregates of probe residue with strong ROS generation efficiency under white light irradiation. Overall, this work presents a strategy of applying ALP-responsive AIE PS for specific imaging cancer cells and succeeding with specific PDT upon the cancer biomarker stimulated responsive reactions.

Microneedle Device Delivering Aggregation-Induced Emission Photosensitizers for Enhanced Metronomic Photodynamic Therapy of Cancer.

Metronomic photodynamic therapy (mPDT), which induces cancer cell death by prolonged intermittent continuous irradiation at lower light power, has profoundly promising applications. However, the photobleaching sensitivity of the photosensitizer (PS) and the difficulty of delivery pose barriers to the clinical application of mPDT. Here, we constructed a microneedle-based device (Microneedles@AIE PSs) that combined with aggregation-induced emission (AIE) PSs to achieve enhanced mPDT for cancer. Due to the strong anti-photobleaching property of the AIE PS, it can maintain superior photosensitivity even after long-time light exposure. The delivery of the AIE PS to the tumor through a microneedle device allows for greater uniformity and depth. This Microneedles@AIE PSs-based mPDT (M-mPDT) offers better treatment outcomes and easier access, and combining M-mPDT with surgery or immunotherapy can also significantly improve the effectiveness of these clinical therapies. In conclusion, M-mPDT offers a promising strategy for the clinical application of PDT due to its better efficacy and convenience.