Aggregation-induced Emission Photosensitizers Research Articles

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.

Indole Aggregation-induced Emission Molecule Based Nanoparticles for Ablation of Mouse Cancer Cells in Vitro

Photodynamic therapy (PDT) holds the merits of high spatiotemporal precision and minimal invasiveness, emerging as the novel therapy. Herein, two aggregation-induced emission photosensitizers (AIE PSs) named TPA-YD and DPA-YD were synthesized for overcoming the dilemma of aggregation-caused fluorescence quenching (ACQ) of conventional photosensitizers. In comparison with DPA-YD, the addition of the benzene ring in TPA-YD enhanced the D-A strength, improved the AIE effect and reactive oxygen species (ROS) generation efficiency. The prepared TPA-YD nanoparticles (TPA-NPs) was promising candidates for PDT.

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.

Molecular Charge and Antibacterial Performance Relationships of Aggregation-Induced Emission Photosensitizers.

Bacterial infections remain a major cause of morbidity worldwide due to drug resistance of pathogenic bacteria. Photodynamic therapy (PDT) has emerged as a promising approach to overcome this drug resistance. However, existing photosensitizers (PSs) are broad-spectrum antibacterial agents that dysregulate the microflora balance resulting in undesirable side effects. Herein, we synthesized a series of aggregation-induced emission (AIE)-active PSs with a lipophilic cationic AIE core with varying charges, named TBTCP and its derivatives. The association of the difference in their molecular charge with the antibacterial effects was systemically investigated. Among the derivatives presented, TBTCP-SF with the electronegative sulfonate group nulled its ability to bind to and ablate Gram-positive (G+) or Gram-negative (G-) bacteria. TBTCP-QY modified by electropositive quaternary ammonium facilitated binding and augmented the photodynamic antibacterial activity for both G+ and G- bacteria. TBTCP-PEG with hydrophilic neutral ligands selectively bound and inactivated G+ bacteria. Under white-light illumination, TBTCP-PEG ablated 99.9% methicillin-resistant Staphylococcus aureus (MRSA) and promoted wound healing in MRSA-infected mice, eliminating MRSA infection both in vitro and in vivo. Our work provides unprecedented insight into the utility of AIE-active PSs for highly targeted and efficient photodynamic ablation of either G+ or G- bacteria that can be translated to next-generation antibacterial materials.

An aggregation-induced emission photosensitizer with efficient singlet oxygen generation capacity for mitochondria targeted photodynamic therapy

A family of near-infrared (NIR) aggregation-induced emission (AIE) photosensitizers (PSs) were designed and synthesized to modulate the spectroscopic and photochemical properties of the contained donor-acceptor (D-A) units. Stronger intermolecular charge transfer (ICT) states were promoted by the synergistic action of benzothiadiazoles and quinolines, which accelerates intersystem crossing (ISC). The best NIR AIE-PS, BTQ, showed an extremely high 1O2 generation rate (5.6-fold of Rose Bengal) and highly efficient photodynamic killing of cancer cells. Furthermore, the mechanism by which mitochondria-targeted PSs produce large amounts of reactive oxygen species (ROS) triggering calcium ion (Ca2+) overload and opening of the mitochondrial permeability transition pore (mPTP), thereby disrupting mitochondria and leading to apoptosis, was demonstrated for the first time. This work provides an exciting benchmark for the molecular engineering of AIE-PSs targeting mitochondria and presented new insights of the development of fluorescence imaging guided photodynamic therapy (FL-G-PDT).

Molecular engineering to construct thieno[3,2-c]pyridinium based photosensitizers for mitochondrial polarity imaging and photodynamic anticancer therapy

Mitochondria are indispensable organelles and have become attractive targets for a lot of diseases. More and more mitochondria targeting photosensitizers (PSs) have been developed for disease diagnosis and photodynamic anticancer therapy. However, current PSs encountered significant limitations, such as short excitation/emission wavelength, low quantum yield (QY), insufficient reactive oxygen species (ROS) generation efficiency. In this study, a series of novel thieno[3,2-c]pyridinium based near-infrared (NIR) aggregation-induced emission PSs (AIE PSs) for targeting mitochondria was rational designed and synthesized by regulating the molecular engineering of D-π-A structure. The synergistic effect of strong D and extended π system fabricated a progressively strong intramolecular charge transfer (ICT) effect to accelerate intersystem crossing (ISC) of excited electrons, which were favorable for the LIQ-TPA-DTZ with NIR emission, good AIE performance, high QY, and high 1O2 and •OH generation efficiency. LIQ-TPA-DTZ can sensitively detect the mitochondrial polarity changes in living cells. Furthermore, it could trigger the mitochondria apoptosis pathway to efficiently photodynamic kill cancer cells and restrain tumor growth in vivo. This work not only provides a powerful tool for mitochondrial targeting imaging and cancer therapy but also offers a facile strategy for constructing thieno[3,2-c] pyridinium based AIE PSs.

Nanospheres of Near-Infrared Aggregation-Induced Emission Probes to Target Mitochondria to Ablate Tumors with Reactive Oxygen Species Generation under Hypoxia

Severe aggregation-caused quenching and the lack of special organelle targeting in conventional photosensitizers (PSs) have limited their advantages in terms of their accurate spatial–temporal control and noninvasive features. Furthermore, severe tumor hypoxia equally diminished the effectiveness of treatment. Herein, a series of aggregation-induced emission (AIE) PSs with precise targeting of organelles are synthesized by simply regulating the molecular structure. The rotation of the donor in the molecule was optimized by altering the tail chain of the triphenylamine derivative, which inhibited nonradiative internal conversion and promoted intersystem crossing to facilitate the free radical generation, and the production efficiency of the type I reactive oxygen species exceeds that of the commercial indicator rose bengal (3-fold). The optimal AIE PS named BETTP can specifically target mitochondria and recognize cancer cells. Simultaneously, live/dead cell costaining assays and flow cytometry validated that BETTP nanoparticles (NPs) have the ability to efficaciously ablate cancer cells in hypoxic conditions after encapsulating BETTP into carriers as nanoparticles. In addition, BETTP NPs also manifest superior performance during near-infrared imaging-guided type I photodynamic therapy in solid tumors. Such BETTP NPs demonstrate the critical feasibility of achieving precise delivery of drugs and targeting of organelles for precise therapy in hypoxic environments, providing a reliable reference for tumor hypoxia challenges.

Molecular engineering to red-shift the absorption band of AIE photosensitizers and improve their ROS generation ability.

Photodynamic therapy (PDT) with aggregation-induced emission photosensitizers (AIE-PSs) has attracted increasing attention for their enhanced fluorescence and reactive oxygen species (ROS) generation abilities upon aggregation. However, it is difficult for AIE-PSs to simultaneously achieve long-wavelength excitation (>600 nm) and high singlet oxygen quantum yield, which restricts their application in deep-tissue PDT. In this study, four novel AIE-PSs were developed by appropriate molecular engineering, and their absorption peaks shifted from 478 to 540 nm with a tail extending to 700 nm. Meanwhile, their emission peaks were also moved from 697 nm to 779 nm with a tail extending over 950 nm. Importantly, their singlet oxygen quantum yields successfully increased from 0.61 to 0.89. Moreover, TBQ, the best photosensitizer developed by us, has been successfully applied to image-guided PDT in BALB/C mice bearing 4T1 breast cancer under red light (605 ± 5 nm) irradiation, with IC50 less than 2.5 μM at a low light dose (10.8 J cm-2). The success of this molecular engineering indicates that increasing the number of acceptors is more effective at red-shifting the absorption band of AIE-PSs than increasing the number of donors, and extending the π-conjugation of acceptors will red-shift the absorption-emission band, increase the maximum molar extinction coefficient, and improve the ROS generation ability of AIE-PSs, thus providing a new strategy for the design of advanced AIE-PSs for deep-tissue PDT.

Development of organic photosensitizers for antimicrobial photodynamic therapy.

Bacterial infection poses a significant threat to human health, and the emergence of antibiotic-resistant strains has exacerbated the situation. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising antibiotic-free treatment option that employs reactive oxygen species (ROS) to cause oxidative damage to bacteria and surrounding biomolecules for treating microbial infections. This review summarizes the recent progress in the development of organic photosensitizers, including porphyrins, chlorophyll, phenothiazines, xanthenes and aggregation-induced emission photosensitizers, for aPDT. A detailed description of innovative therapeutic strategies that rely on the infection microenvironment or the unique structural properties of bacteria to amplify the therapeutic effects is provided. Moreover, the combination of aPDT with other therapy strategies such as antimicrobial peptide therapy, photothermal therapy (PTT) or gas therapy, is described. Finally, the current challenges and perspectives of organic photosensitizers for clinical antibacterial applications are discussed.

Novel aggregation-induced emission-photosensitizers with built-in capability of mitochondria targeting and glutathione depletion for efficient photodynamic therapy.

Owing to its non-invasive feature and excellent therapeutic effect, photodynamic therapy has received considerable interest in cancer therapy. However, the therapeutic efficacy of photodynamic therapy is limited by some intrinsic drawbacks of photosensitizers such as aggregation-caused quenching and non-specificity towards cellular organelles. Moreover, the overexpressed glutathione in tumour cells which exhibits a potent scavenging effect on reactive oxygen species generated during the photodynamic therapy process also reduces the efficacy of photodynamic therapy. Therefore, the synthesis of aggregation-induced emission based photosensitizers with cellular organelle targeting and glutathione-depletion capability is highly desirable in photodynamic therapy. Here, two new aggregation-induced emission based photosensitizers namely tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid (TPEPy-BA) and tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid pinacol ester (TPEPy-BE) were synthesized which easily aggregated under aqueous conditions and showed bright emission in the near infra-red region. Furthermore, these photosensitizers were encapsulated into an amphiphilic block copolymer (DSPE-PEG) to improve the aqueous stability and cellular internalization of photosensitizers. The developed photosensitizer nanoparticles showed high reactive oxygen species generation efficacy, mitochondria-targeting and glutathione-depletion capability. The results showed that tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid pinacol ester nanoparticles exhibited a highly efficient photodynamic ablation of MCF-7 cells compared to tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid nanoparticles, upon white light irradiation, due to its high intracellular reactive oxygen species generation efficiency and mitochondria-dysfunction ability. Moreover, tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid pinacol ester nanoparticles produced a glutathione-depleting adjuvant, quinone methide, which greatly reduced the glutathione level in cancer cells, thus enhancing the efficacy of photodynamic therapy. This study provides a new strategy for the synthesis of aggregation-induced emission based photosensitizers with combined mitochondria-targeting and glutathione-depletion capability for efficacious photodynamic therapy.

Construction of aggregation-induced emission photosensitizers based on supramolecular polymers for enhanced photocatalytic oxidative coupling of amines

In this study, we have constructed a supramolecular polymer with aggregation-induced emission through host–guest interactions, which can be used as photocatalysts for photocatalytic oxidative coupling reaction of amines to imines.

Molecular engineering to enhance the reactive oxygen species generation of AIEgens and exploration of their versatile applications.

Fluorescent dyes with aggregation-induced emission (AIE) characteristics have shown potential applications in the fields of biological imaging, photodynamic therapy and photothermal therapy, in which photosensitizers (PSs) play a crucial role. However, how to design high-quality PSs with high reactive oxygen species (ROS) generation efficiency remains unclear. In this contribution, an effective molecular design strategy to improve the ROS generation efficiency of AIE PSs was proposed. A series of tetraphenylethylene derivatives containing the pyridine ring or pyridinium with different substituents were designed and synthesized. All the molecules were weakly emissive when molecularly dissolved in solution but displayed intense emission upon aggregation, demonstrating a phenomenon of AIE characteristic. Pyridinium molecules could be used as visualization agents to specifically stain the mitochondria in living cells, while most of the molecules failed to generate ROS upon white light irradiation. In contrast, TPE-Pys-BP containing benzophenone produced ˙OH and 1O2 efficiently in the presence of light due to its large spin-orbit coupling constant to promote efficient intersystem crossing. Such a property allowed TPE-Pys-BP to serve as a PS to kill cancer cells using photodynamic therapy. TPE-Pys-BP also exhibited mechanochromic luminescence (ML), and its emission could be reversibly switched between two distinct colors through repeated grinding and fuming processes. A security paper was fabricated using the ML properties of TPE-Pys-BP.

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.

Synergistically Enhancing Tumor Chemotherapy Using an Aggregation-Induced Emission Photosensitizer on Covalently Conjugated Molecularly Imprinted Polymer Nanoparticles.

Due to the polygenic and heterogeneous nature of the tumorigenesis process, traditional chemotherapy is far from desirable. Fabricating multifunctional nanoplatforms integrating photodynamic effect can synergistically enhance chemotherapy because they can make the cancer cells much sensitive to chemotherapeutics. However, how to assemble different units in nanoplatforms and minimize side effects caused by chemodrugs and photosensitizers (PSs) still needs to be explored. Herein, a nanoplatform CPP/PS-MIP@DOX is developed using a simultaneously covalently conjugated new aggregation-induced emission (AIE) PS and a cell-penetrating peptide (CPP) on the surface of silica-based molecularly imprinted polymer (MIP) nanoparticles, prepared with doxorubicin (DOX) as the template in the water system via a sol-gel technique. CPP/PS-MIP@DOX has good biocompatibility, high DOX-loading ability, promoted cellular uptake, and sustained and pH-sensitive drug release capability. Furthermore, it can efficiently penetrate into tumor tissue, accurately home to, and accumulate at the tumor site. As a result, a better efficacy with lower cytotoxicity is achieved with a smaller dosage of DOX by utilizing either the photodynamic effect or unique characteristics of the MIP. It is the first nanoplatform fabricated by chemically conjugating AIE PSs directly on the surface of the scaffold via the surface-decorated strategy and successfully applied in cancer therapy. This work provides an effective strategy by constructing AIE PS-based cancer nanomedicines with MIPs as scaffolds.

Aggregation-Induced-Emission Photosensitizer-Loaded Nano-Superartificial Dendritic Cells with Directly Presenting Tumor Antigens and Reversed Immunosuppression for Photodynamically Boosted Immunotherapy.

The success of tumor immunotherapy highlights the potential of harnessing immune system to fight cancer. Activating both native T cells and exhausted T cells is a critical step for generating effective antitumor immunity, which is determined based on the efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells, as well as immunosuppressive reversal. However, strategies for achieving an efficient antigen presentation process and improving theimmunosuppressive microenvironment remain unresolved. Here, aggregation-induced-emission (AIE) photosensitizer-loaded nano-superartificial dendritic cells (saDC@Fs-NPs) are developed by coating superartificial dendritic cells membranes from genetically engineered 4T1 tumor cells onto nanoaggregates of AIE photosensitizers. The outer cell membranes of saDC@Fs-NPs are derived from recombinant lentivirus-infected 4T1 tumor cells in which peptide-major histocompatibility complex class I, CD86, and anti-LAG3 antibody are simultaneously anchored. These saDC@Fs-NPs could directly stimulate T-cell activation and reverse T-cell exhaustion for cancer immunotherapy. The inner AIE-active photosensitizers induce immunogenic cell death to activate dendritic cells and enhance T lymphocyte infiltration by photodynamic therapy, promoting the transformation of "cold tumors" into "hot tumors," which further boostsimmunotherapy efficiency. This work presents a powerful photoactive and artificial antigen-presenting platform for activating both native T cells and exhausted T cells, as well as facilitating tumor photodynamic immunotherapy.

Short-Wavelength Aggregation-Induced Emission Photosensitizers for Solid Tumor Therapy: Enhanced with White-Light Fiber Optic.

White-light photodynamic therapy (wPDT) has been used in the treatment of cancer due to its convenience, effectiveness and less painful. However, the limited penetration of white-light into the tissues leads to a reduced effectiveness of solid tumor treatment. Two short-wavelength aggregation-induced emission (AIE) nanoparticles were prepared, PyTPA@PEG and TB@PEG, which have excitation wavelengths of 440 nm and 524 nm, respectively. They were characterized by UV, fluorescence, particle size and TEM. The ability of nanoparticles to produce reactive oxygen species (ROS) and kill cancer cells under different conditions was investigated in vitro, including white-light, after white-light penetrating the skin, laser. A white-light fiber for intra-tumor irradiation was customized. Finally, induced tumor elimination with fiber-mediated wPDT was confirmed in vivo. In vitro, both PyTPA@PEG and TB@PEG are more efficient in the production ROS when exposed to white-light compared to laser. However, wPDT also has a fatal flaw in that its level of ROS production after penetrating the skin is reduced to 20-40% of the original level. To this end, we have customized a white-light fiber for intra-tumor irradiation. In vivo, the fiber-mediated wPDT significantly induces tumor elimination with maximized therapeutic outcomes by irradiating the interior of the tumor. In addition, wPDT also has the advantage that its light source can be adapted to a wide range of photosensitizers (wavelength range 400-700 nm), whereas a laser of single wavelength can only target a specific photosensitizer. This method of using optical fiber to increase the tissue penetration of white light can greatly improve the therapeutic effect of AIE photosensitizers, which is needed for the treatment of large/deep tumors and holds great promise in cancer treatment.