Aggregation-caused Quenching Effect Research Articles

AIEgens for Bacterial Imaging and Ablation

Accurate and sensitive diagnosis of pathogenic bacterial infection is a fundamental first step for correct bacteria management, helping to avoid the development of drug-resistant bacteria caused by the inappropriate use and overuse of antibiotics. Fluorescence probes as a promising visual tool can help identify pathogens rapidly and reliably. However, rigidly structured traditional fluorescence probes generally suffer from the drawback of aggregation-caused quenching (ACQ) effect, which greatly undermines their advantages with respect to sensitivity. Luminogens with aggregation-induced emission properties, namely AIEgens, can overcome the ACQ effect and certain AIEgen-based materials are capable of generating reactive oxygen species (ROS) in the aggregate states. Hence, they have become powerful tools for imaging and killing bacteria. This review summarizes the recent advances in AIEgens for the diagnosis and treatment of pathogen infections. Special attention has been paid to the molecular design, the application in bacterial imaging and ablation in vitro and in vivo, and the biocompatibility of AIEgens. Finally, the challenges and prospects are discussed in terms of using AIEgens to advance precision therapies for pathogen infections.

BOPHY-Based Aggregation-Induced-Emission Nanoparticle Photosensitizers for Photodynamic Therapy

Photosensitizers for photodynamic therapy (PDT) of cancer have been widely investigated over the past decades. However, the notorious aggregation-caused quenching (ACQ) effect limits their further biological applications. In this work, we have designed and reported a photosensitizer BOPHY-2TPA. The formed photosensitizer BOPHY-2TPA was a donor–acceptor–donor (D–A–D) structure with the BOPHY as an acceptor core and two triphenylamine (TPAs) as the electron donor units. The BOPHY-2TPA exhibited a large Stokes shift and excellent photoinduced 1O2 generation capabilities. Besides, the twisted structure of TPAs endowed the BOPHY-2TPA with intrinsic AIE properties, which effectively avoided the ACQ effect. Because of these prominent features, the BOPHY-2TPA aggregates encapsulated with biocompatible Pluronic P123 in aqueous solution showed high PDT antitumor efficiency.

Porphyrin with circularly polarized luminescence in aggregated states

Porphyrin with circularly polarized luminescence (CPL) in aggregated state was seldom presented due to the strong aggregation-caused quenching (ACQ) effect at aggregation. This work designed and synthesized a novel porphyrin derivative (CPL-P) with good CPL behaviour in aggregated states based on the strong AIE-FRET effect and good chirality transfer of liquid crystalline porphyrin, which was constructed by using porphyrin unit as core with four AIE cyanostilbene groups bearing peripheral chiral alkyl chains. CPL-P exhibited orderly hexagonal columnar mesophase between 62.5 °C and 113.2 °C. It displayed excellent fluorescence emission at 640–760 nm in aggregated states due to the AIE-FRET effect between cyanostilbene unit and porphyrin moiety. Moreover, CPL-P showed the strong circular dichroism and CPL properties in aggregated states based on the effective chiral transfer of the spiral liquid crystalline self-assembly. The |glum| value for mesophase attained 6.6 × 10−3 based on the combining effect of AIE-FRET and chiral transfer. This research supplied a new strategy for transferring typical achiral porphyrin with ACQ effect to luminescent molecule with good CPL behaviour in aggregated state.

Pyrene-Based Nonwoven Fabric with Tunable Fluorescence Properties by Employing the Aggregation-Caused Quenching Effect.

Conventional aromatic compounds tend to exhibit the formation of sandwich-shaped excimers and exciplexes between their excited and ground states at high concentrations or in their aggregated states, causing their fluorescence to weaken or disappear due to the aggregation-caused quenching (ACQ) effect. This limits their applications in concentrated solutions or solid materials. Herein, for the first time, ACQ-based pyrene (Py) units are covalently connected to the surface of polyethylene/polypropylene nonwoven fabric (PE/PP NWF) via electron beam preradiation-induced graft polymerization followed by chemical modification. The matrix can be considered a solid solvent and Py units as a solid solute, such that the amount of Py units can be controlled by varying the reaction time. The obtained fluorescent fabric not only exhibits remarkable fluorescence properties with high fluorescence intensity, high quantum yield (>90%), and excellent fluorescence stability after laundering or in harsh chemical environments, but the fluorescence color and intensity, quantum yield, and lifetime can also be regulated by employing the ACQ effect. Additionally, the as-prepared fluorescent fabric can effectively distinguish common monocyclic aromatic hydrocarbons via a simple fluorescence response test.

Linear and high-molecular-weight poly-porphyrins for efficient photodynamic therapy.

Photodynamic therapy (PDT) holds great potential in cancer treatment due to the advantages of non-invasiveness, negligible side-effect, and high spatiotemporal selectivity. Porphyrin is the most widely used photosensitizer in clinical treatment. However, its PDT efficacy is always limited by the undesired aggregation caused quenching (ACQ) effect originating from the planar and rigid structure. In this work, a linear polymeric porphyrin with "structure defects" was developed to overcome the ACQ effect for most of the photosensitizers with conjugated macrocycles. Compared to porphyrin monomers, poly-porphyrins could improve singlet oxygen generation ability, and the singlet oxygen quantum yield enhanced with increasing molecular weight of poly-porphyrins. To achieve efficient in vivo PDT, PEG and acetazolamide were conjugated to the optimized poly-porphyrins to afford pP-PEG-AZ nanoparticles (pP-PEG-AZ NPs) with excellent stability, efficient in vitro intracellular internalization, negligible dark-toxicity, notable photo-toxicity, and in vivo anti-cancer efficacy based on combined PDT and anti-angiogenesis therapy.

Photosensitizer-driven nanoassemblies of homodimeric prodrug for self-enhancing activation and synergistic chemo-photodynamic therapy.

Carrier-free prodrug-nanoassemblies have emerged as promising nanomedicines. In particular, the self-assembled nanoparticles (NPs) composed of homodimeric prodrugs with ultrahigh drug loading have attracted broad attention. However, most homodimeric prodrugs show poor self-assembly ability due to their symmetric structures. Herein, we developed photosensitizer-driven nanoassemblies of homodimeric prodrug for self-enhancing activation and chemo-photodynamic synergistic therapy.Methods: In this work, a pyropheophorbide a (PPa)-driven nanoassemblies of an oxidation-responsive cabazitaxel homodimer (CTX-S-CTX) was fabricated (pCTX-S-CTX/PPa NPs). The assembly mechanisms, aggregation-caused quenching (ACQ) effect alleviation, singlet oxygen generation, self-enhancing prodrug activation, cellular uptake, intracellular reactive oxygen species (ROS) generation and synergistic cytotoxicity of pCTX-S-CTX/PPa NPs were investigated in vitro. Moreover, the pharmacokinetics, ex vivo biodistribution and in vivo therapeutic efficacy of pCTX-S-CTX/PPa NPs were studied in mice bearing 4T1 tumor.Results: Interestingly, PPa was found to drive the assembly of CTX-S-CTX, which cannot self-assemble into stable NPs alone. Multiple intermolecular forces were found to be involved in the assembly process. Notably, the nanostructure was destroyed in the presence of endogenous ROS, significantly relieving the ACQ effect of PPa. In turn, ROS generated by PPa under laser irradiation together with the endogenous ROS synergistically promoted prodrug activation. As expected, the nanoassemblies demonstrated potent antitumor activity in a 4T1 breast cancer BALB/c mice xenograft model.Conclusion: Our findings offer a simple strategy to facilitate the assembly of homodimeric prodrugs and provide an efficient nanoplatform for chemo-photodynamic therapy.

Pure-Blue Fluorescence Molecule for Nondoped Electroluminescence with External Quantum Efficiency Approaching 13%

A pure-blue light-emitting material is one of the key components in the preparation of organic light-emitting diode (OLED) displays. Although high-efficiency blue OLEDs have been realized in therma...

Aggregology: Exploration and innovation at aggregate level

Aggregology: Exploration and innovation at aggregate level

Two Ru(II) compounds with aggregation induced emission as promising photosensitizers for photodynamic therapy

Design and preparation of photosensitizers (PSs) play an important role in photodynamic therapy (PDT). PDT mainly relies on the production of toxic reactive oxygen species (ROS) of the PSs. Conventional fluorophores, however, often suffer from aggregation caused quenching (ACQ), which limits the potential of PSs as fluorescent imaging agents. Molecules with aggregation-induced emission (AIE) properties maintain high fluorescence and dispersity in aqueous solutions, overcoming the ACQ effect. Ruthenium (II)-based AIE compounds are highly biocompatible molecules and can be used for response cell imaging. In the current study, two novel Ru(II)-based AIE compounds with main ligands 1,3-di(2H-tetrazol-5-yl)benzene (Hphbtz) by changing auxiliary ligand 2,2′-bipyridine (bipy) and 1,10-phenanthroline (phen) have been successfully synthesized and characterized, [Ru(Hphbtz)(bipy)2][PF6] (1) and [Ru(Hphbtz)(phen)2][PF6] (2). The NPs show strong intra-cellular fluorescence and also simultaneously exhibited potent cytotoxic activity. These compounds can self-assemble to form nanoparticles (NPs) by nanoprecipitation. The compounds are found to exhibit a high AIE property with emission maxima at 353 nm and 380 nm, respectively. And the compounds have the low IC50 (half maximal inhibitory concentration) of only 15 μg/mL (1.94 μM) and 13 μg/mL (1.58 μM) on HeLa cells, respectively. Meanwhile, negligible dark toxicity has been also observed for these NPs. The results show that [Ru(Hphbtz)(bipy)2][PF6] (1) and [Ru(Hphbtz)(phen)2][PF6] (2) NPs can inhibit cell proliferation in vitro, and may be potential candidates for photodynamic therapy.

AIEgens: An emerging fluorescent sensing tool to aid food safety and quality control.

As a global public health problem, food safety has attracted increasing concern. To minimize the risk exposure of food to harmful ingredients, food quality and safety inspection that covers the whole process of "from farm to fork" is much desired. Fluorescent sensing is a promising and powerful screening tool for sensing hazardous substances in food and thus plays a crucial role in promoting food safety assurance. However, traditional fluorphores generally suffer the problem of aggregation-caused quenching (ACQ) effect, which limit their application in food quality and safety inspection. In this regard, luminogens with aggregation-induced emission property (AIEgens) showed large potential in food analysis since AIEgens effectively surmount the ACQ effect with much better detection sensitivity, accuracy, and robustness. In this contribution, we review the latest developments of food safety monitoring by AIEgens, which will focus on the molecular design of AIEgens and their sensing principles. Several examples of AIE-based sensing applications for screening food contaminations are highlighted, and future perspectives and challenges in this emerging field are tentatively elaborated. We hope this review can motivate new research ideas and interest to aid food safety and quality control, and facilitate more collaborative endeavors to advance the state-of-the-art sensing developments and reduce actual translational gap between laboratory research and industrial production.

Fluorescent nanoparticles with ultralow chromophore loading for long-term tumor-targeted imaging

Recently, organic dyes with aggregation-induced emission (AIE) have attracted much attention in bioimaging and diagnostics. Relatively, the application of traditional dyes has diminished because of aggregation-caused quenching (ACQ). In this work, we compare the imaging ability of nanoparticle formulations of these two kinds of dyes. Boron dipyrromethene (BODIPY) was chosen as a representative of the ACQ dyes, and an aggregation-induced emission (AIE) dye BPMT was used for comparison. BODIPY and BPMT were entrapped into PEG5k-PLA10k to form BODIPY-loaded NPs (BNPs) and BPMT-loaded NPs (ANPs), respectively. In vivo and ex vivo imaging demonstrated that BNP1 with ultralow BODIPY load (0.07%) can effectively accumulate in tumor tissues and enable long-term noninvasive imaging. In contrast, ANP4 with high BPMT load (1.6%) has poor bioimaging ability. In general, our work has certain reference significance for the application of ACQ dyes and AIEgens in bioimaging, diagnostics, and theranostics. Statement of SignificanceIn this work, Boron dipyrromethene (BODIPY) was chosen as a representative of ACQ dyes. As a control, (Z)-2-(4′-(9H-carbazol-9-yl)-[1,1′-biphenyl]-4-yl)-3-(7-(4-(bis(4methoxyphenyl)amino) phenyl) benzo[c] [1,2,5] thiadiazol-4-yl) acrylonitrile (BPMT) was selected as an aggregation-induced emission (AIE) dye. BODIPY and BPMT was entrapped into PEG5k-PLA10k to form BODIPY-loaded NPs (BNPs) and BPMT-loaded NPs (ANPs), respectively. In vivo and ex vivo imaging demonstrated that BNP1 with ultralow BODIPY load (0.07%) can effectively accumulate in tumor tissues and realize long-term noninvasive imaging. The weaknesses of ACQ effect can be converted into advantages by skillful use of nanotechnology, which can not only save the cost but also realize high efficiency targeted cancer imaging.

Constructing a Local Hydrophobic Cage in Dye-Doped Fluorescent Silica Nanoparticles to Enhance the Photophysical Properties.

Aggregation-caused quenching (ACQ) and poor photostability in aqueous media are two common problems for organic fluorescence dyes which cause a dramatic loss of fluorescence imaging quality and photodynamic therapy (PDT) failure. Herein, a local hydrophobic cage is built up inside near-infrared (NIR) cyanine-anchored fluorescent silica nanoparticles (FSNPs) in which a hydrophobic silane coupling agent (n-octyltriethoxysilane, OTES) is doped into FSNPs for the first time to significantly inhibit the ACQ effect and inward diffusion of water molecules. Therefore, the obtained optimal FSNP-C with OTES-modification can provide hydrophobic repulsive forces to effectively inhibit the π–π stacking interaction of cyanine dyes and simultaneously reduce the formation of strong oxidizing species (•OH and H2O2) in reaction with H2O, resulting in the best photostability (fluorescent intensity remained at 90.1% of the initial value after 300 s of laser scanning) and a high PDT efficiency on two- and three-dimensional (spheroids) HeLa cell culture models. Moreover, through molecular engineering (including increasing covalent anchoring sites and steric hindrance groups of cyanine dyes), FSNP-C exhibits the highest fluorescent intensity both in water solution (12.3-fold improvement compared to free dye) and living cells due to the limitation of molecular motion. Thus, this study provides an effectively strategy by combining a local hydrophobic cage and molecular engineering for NIR FSNPs in long-term bright fluorescence imaging and a stable PDT process.

Facile Preparation of Stable Solid-State Carbon Quantum Dots with Multi-Peak Emission.

Aggregation-caused quenching (ACQ) effect, known as the main cause to restrain solid-state luminescence of carbon quantum dots (CQDs), hinders further application of CQDs in white light-emitting diodes (WLED). Here, a complex of CQDs and phthalimide crystals (CQDs/PC) was prepared through a one-step solvothermal method. CQDs/PC prevented CQDs from touching directly by embedding the CQDs in phthalimide crystal matrix in situ, which effectively reduced the ACQ effect. Furthermore, CQDs/PC exhibited multi-peak fluorescence spectra that span the green, yellow and orange spectral regions. Finally, a WLED fabricated based on CQDs/PC achieved a color-rendering index of 82 and a correlated color temperature of 5430 K. This work provides a quick and effective strategy to apply CQDs to WLED.

Application of AIE-active probes in fluorescence sensing

Fluorescent probes that exhibit distinct advantages of high sensitivity, good selectivity, fast response speed, etc., have been widely applied in diverse sensing areas. However, the fluorescence of traditional organic probes tends to decrease or be quenched at high concentration or in aggregate state due to the aggregation-caused quenching (ACQ) effect, which limits their application in sensing areas. In 2001, our group coined the concept of aggregation-induced luminescence (AIE), which is exactly opposite to the ACQ effect and refers to a unique phenomenon that a kind of non- or weakly emissive luminogens in dilute solutions are induced to emit intensely upon aggregation or in solid state. Thus, the AIE-active luminogens (AIEgens) provide an alternative to solve this difficulty. Thanks to their intrinsic advantages, the fluorescent sensors based on AIEgens show lower background, higher signal-to-noise ratio and more outstanding resistance to photobleaching etc. Moroever, the AIE probes not only could overcome the problem encountered by ACQ ones, but also achieve faster and more sensitive detection of the targets. Thus, using AIE probes to detect a wide varity of targets is one of the hot research areas. To highlight the progress in this area, herein, we briefly summarize the sensing applications of AIEgens. First, we introduced the AIE probes used in the detection of ions, including K+, Hg2+, Fe3+, CN−, ClO−, PO43−, etc. Notably, the fluorescent probes based on AIEgen could realize the selective detection of various ions not only in the organic solutions, but also in aqueous solutions. Next, we discussed the detection of low mass molecules using AIE probes for they play a very important role in life activities and their content can reflect the health status and life information of an organism. The used low mass molecules include gas (NH3, CO2, H2S), explosive (PA, TNT), biothiol (Gys, GSH), and ATP and so on. Third, we summarized the qualitative and quantitative sensing of biomacromolecules, such as DNA, proteins, enzyme, by AIE probes, which is critical to the life sciences, biotechnology, and pharmaceutical industries. Fourth, the application of AIE probes in the fields like pH response, cell membrane imaging, mitochondrial imaging and fungal detection are reviewed. Finally, the prospects for the design and application of AIE probes are presented. We hope that this review will stimulate interests in AIE-based sensors and provide some new ideas for researchers working in this area.

Janus macromolecular brushes for synergistic cascade-amplified photodynamic therapy and enhanced chemotherapy

The aggregation-caused quenching (ACQ) effect of photosensitizers and multidrug resistance are the major obstacles in photodynamic therapy (PDT) and chemotherapy, respectively. Synergistic photo-chemotherapy is a promising cancer treatment to overcome the short boards of each single therapy. However, the fabrication of nanocarriers acting as both photosensitizers in PDT and the vehicle of drug release is a key challenge. Herein, we constructed a well-defined porphyrin-containing Janus macromolecular brush and used it as both a photosensitizer and a pH-responsive vehicle for DOX release. The Janus macromolecular brush with pH-responsive side chains and porphyrin units linked covalently in each repeat unit was synthesized by the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. The high grafting content of porphyrin units in the macromolecular brush improved the DOX loading capability by π–π stacking and therefore reduced the total treatment dose of DOX-loaded macromolecular brush nanoparticles (NPs). The pH-responsive side chains played triple roles in synergistic cascade-amplified PDT and enhanced chemotherapy including an executor of controlled drug release, a ligand with a mitochondria-targeting feature, and a barrier to reduce the ACQ effect of porphyrin units. In vitro and in vivo studies confirmed that the DOX-loaded macromolecular brush NPs exhibited high phototoxicity and significant tumor inhibition efficacy. Statement of SignificanceSynergistic photodynamic therapy (PDT) and chemotherapy has emerged as a promising cancer treatment to overcome the challenges of a single modality. Herein, we constructed new pH-responsive vesicles using porphyrin-containing Janus macromolecular brushes as theranostic nanocarriers to encapsulate high-loading doxorubicin (DOX) for synergistic cascade-amplified PDT and enhanced chemotherapy. The high grafting content of porphyrin units in Janus macromolecular brushes improved DOX loading capability by π–π stacking for enhanced chemotherapy. Moreover, pH-responsive side chains subsequently enhanced the suppression of the aggregation-caused quenching (ACQ) effect of porphyrins for cascade-amplified PDT. In vitro and in vivo studies confirmed that DOX-loaded macromolecular brush nanoparticles exhibited high phototoxicity and significant tumor inhibition efficacy.

Modular Design of Peptide- or DNA-Modified AIEgen Probes for Biosensing Applications.

Fluorophore probes are widely used for bioimaging in cells, tissues, and animals as well as for monitoring of multiple biological processes in complex environments. Such imaging properties allow scientists to make direct visualizations of pathological events and cellular targets. Conventional fluorescent molecules have been developed for several decades and achieved great successes, but their emissions are often weakened or quenched at high concentrations that might suffer from the aggregation-caused quenching (ACQ) effect, which reduces the efficiencies of their applications. In contrast to the ACQ effect, aggregation-induced emission (AIE) luminogens (AIEgens) display much higher fluorescence in aggregated states and possess various advantages such as low background, long-term tracking ability, and strong resistance to photobleaching. Therefore, AIEgens are employed as unique fluorescence molecules and building blocks for biosensing applications in the fields of ions, amino acids, carbohydrates, DNAs/RNAs, peptides/proteins, cellular organelles, cancer cells, bacteria, and so on. Quite a few of the above biosensing missions are accomplished by modular peptide-modified AIEgen probes (MPAPs) or modular DNA-modified AIEgen probes (MDAPs) because of the multiple capabilities of peptide and DNA modules, including solubility, biocompatibility, and recognition. Meanwhile, both electrostatic interactions and coupling reactions could provide efficient methods to construct different MPAPs and MDAPs, finally resulting in a large variety of biosensing probes. Those probes exhibit leading features of detecting nucleic acids or proteins and imaging mass biomolecules. For example, under modular design, peptide modules possessing versatile recognition abilities enable MPAPs to detect numerous targets, such as integrin αvβ3, aminopeptidase N, MMP-2, MPO, H2O2, and so forth; MDAP could allow the imaging of mRNA in cells and tissue chips, suggesting the diagnostic functions of MDAP in clinical samples. Modular design offers a novel strategy to generate AIEgen-based probes and expedites functional biomacromolecules research. In this vein, here we review the progress on MPAPs and MDAPs in the most recent 10 years and highlight the modular design strategy as well as their advanced biosensing applications including briefly two aspects: (1) detection and (2) imaging. By the use of MPAPs/MDAPs, multiple bioanalytes can be efficiently analyzed at low concentrations and directly visualized through high-contrast and luminous imaging. Compared with MPAPs, the quantities of MDAPs are limited because of the difficult synthesis of long-length DNA strands. In future work, multifunctional of DNA sequences are needed to explore varieties of MDAPs for diverse biosensing purposes. At the end of this Account, some deficiencies and challenges are mentioned for briging more attention to accelerate the development of AIEgen-based probes.

Revealing aggregation-induced emission effect of imidazolium derivatives and application for detection of Hg2+

Despite being highly emissive in solution, aggregation of 4-(4,5-bis(4-methoxyphenyl)-1H- imidazole-2-yl) benzaldehyde (BMI) molecules typically results in the quenching of fluorescence. To overcome the shortcomings of aggregation-caused quenching (ACQ), the substituent of imidazole in the nitrogen atom of the BMI have been found as a conformation function group (CFG) to turn the aggregation-induced emission (AIE) effect. The introduction of CFG not only causes the restriction of intramolecular rotations (RIR) effect, but also attenuates the coplanarity of the molecule. As a result, the BMI with ACQ effect is transformed into BMIs with AIE effect. As the steric hindrance of the CFG increases, the AIE characteristic of the derivative also becomes apparent. With the assistance of the thioacetal unit, BMIBD can act as an outstanding probe for the detection of Hg2+ with high sensitivity and selectivity. A series of characterizations were implemented to prove the unique response mechanism of BMIBD toward mercury ions, including optical behavior investigation, mass analysis and 1H NMR studies. Further, the detection limit is low up to 36 nM. Taking advantages of excellent optical properties of this AIE probe BMIBD, point-of-care testing (POCT) for Hg2+ detection was further investigated. Meanwhile, BMIBD presented the desirable analytical property for the real water samples. Additionally, cellular imaging experiment revealed that the probe has an excellent biocompatibility that could be applied for tracking Hg2+ in living cells.

Aggregation-Caused Quenching-Type Naphthalimide Fluorophores Grafted and Ionized in a 3D Polymeric Hydrogel Network for Highly Fluorescent and Locally Tunable Emission

Polymer hydrogels with intense yet tunable fluorescence are of great research interest due to their wide potential use in biological imaging, sensing, information storage, etc. However, the conventional fluorophores such as naphthalimide and its derivatives are usually not recommended to prepare highly fluorescent hydrogels because of their aggregation-caused quenching (ACQ) nature and spontaneous tendency to undergo fluorescence self-quenching in quasi-solid-state hydrogel systems. Additionally, local regulation over fluorescent behavior of hydrogels, despite being important, still remains underdeveloped. Herein, we report highly fluorescent polymeric hydrogels based on conventional ACQ-type naphthalimide fluorophores, followed by spatial and temporal control of their fluorescent behavior. The hydrogels were prepared by one-pot radical copolymerization of naphthalimide-containing monomer and acrylamide in chitosan-acetic acid solution. Their intense emission comes from synergetic anchoring and diluting effect of the protonated naphthalimide moieties grafted on polymer chains, which result in the electrostatic repulsion among ACQ luminogens and reduced PET (photoinduced electron transfer) effect from adjacent dimethylamine groups to naphthalimide fluorophores. After being deprotonated in alkaline conditions, both PET and the ACQ effect work again to greatly quench fluorescence, endowing the hydrogels with pH-sensitive emission behavior. These properties encourage us to develop a diffusion-reaction (D-R) method to spatially and temporally control their fluorescent behavior. Based on these results, the ion-transfer-printing-assisted D-R method was further developed to fabricate many high-precision and meaningful fluorescent patterns on hydrogels. These fluorescent patterns are invisible under daylight but become vivid under specific UV light illumination, suggesting their wide potential applications in information security and transmission.

Photodynamic PEG-coated ROS-sensitive prodrug nanoassemblies for core-shell synergistic chemo-photodynamic therapy

The combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEG-coated prodrug nanoplatform for core–shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG2k). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG2k polymer. Then, a core–shell nanoassembly is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG2k. PPa-PEG2k serves for both PEGylation and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG2k not only is used for PDT but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEG-coated nanoassemblies demonstrated synergistic antitumor activity in vivo. Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEG shell, provides a new strategy for synergistic chemo-photodynamic therapy. Statement of SignificationThe combination of chemotherapy with photodynamic therapy (PDT) holds promising prospects in cancer therapy. However, it remains a tremendous challenge to effectively co-deliver chemotherapeutic drugs and photosensitizers into tumors. Herein, we construct a photodynamic PEGylation-coated prodrug-nanoplatform for high-efficiency synergistic cancer therapy, which is composed of a light-activatable PPa-PEG2k shell and a ROS-responsive paclitaxel (PTX) prodrug core. The PPa-PEG2k-generated ROS not only was used for synergistic PTX release but also synergistically facilitated tumor cell apoptosis in combination with PTX-initiated chemo-cytotoxicity. The light-activatable nanoassemblies exhibited multiple drug delivery advantages including high co-loading efficiency, self-enhanced PTX release, extended circulation time, favorable biodistribution, and potent synergistic anticancer activity. Our findings provide a new strategy for the rational design of advanced nano-DDS for high-efficiency combinational chemo-photodynamic therapy.

Photodynamic PEGylation Coated Prodrug-Nanoassemblies for Core-Shell Synergistic Chemo-Photodynamic Therapy

Combination of chemotherapy with photodynamic therapy (PDT) holds promising applications in cancer therapy. However, co-encapsulation of chemotherapeutic agents and photosensitizers (PS) into the conventional nanocarriers suffers from inefficient co-loading and aggregation-caused quenching (ACQ) effect of PS trapped in dense carrier materials. Herein, we report a light-activatable photodynamic PEGylation-coated prodrug-nanoplatform for core-shell synergistic chemo-photodynamic therapy. A novel photodynamic polymer is rationally designed and synthesized by conjugating pyropheophorbide a (PPa) to polyethylene glycol 2000 (PEG2k). PPa is used as the hydrophobic and photodynamic moiety of the amphipathic PPa-PEG2k polymer. Then, a core-shell nanoassemblies is prepared, with an inner core of a reactive oxygen species (ROS)-responsive oleate prodrug of paclitaxel (PTX) and an outer layer of PPa-PEG2k. PPa-PEG2k serves both for PEGylation modification and PDT. Instead of being trapped in the inner core, PPa in the outer PPa-PEG2k layer significantly alleviates the ACQ effect. Under laser irradiation, ROS generated by PPa-PEG2k is not only used for PDT, but also synergistically promotes PTX release in combination with the endogenous ROS overproduced in tumor cells. The photodynamic PEGylation coated nanoassemblies demonstrated synergistic antitumor activity in vivo. Such a unique nanoplatform, with an inner chemotherapeutic core and an outer photodynamic PEGylation shell, provides a new strategy for synergistic chemo-photodynamic therapy.