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Development of new photosensitizers (PSs) with high singlet oxygen quantum yield and minimal side effects is of great interest in photodynamic therapy (PDT). Herein, a facile strategy to significan...

Photodynamic therapy (PDT) is an efficacious noninvasive therapeutic modality that utilizes nontoxic photosensitizers (PSs) to transform oxygen into highly cytotoxic reactive oxygen species (ROS) u...

Summary In conventional photodynamic therapy (PDT), reactive oxygen species are produced to kill cancer cells based on type-I and type-II mechanisms, and the sensitization of photosensitizers is oxygen dependent. However, solid tumors reside in a hypoxic milieu, which hampers the therapeutic efficacy of photosensitive drugs against tumors. Novel photosensitizers NBEX (X = S, Se, Te) were designed to bind to RNA without interference by other species and to transfer excitation-state energy directly to destroy RNA in cancer cells. This process of killing cancer cells is completely independent of oxygen (type-III mechanism). Remarkably, NBEX (X = S, Se, Te) could self-assemble into nanoparticles and accumulate in the tumor area within tens of minutes in vivo. NBESe exhibited an excellent performance for killing solid tumors and inhibited tumor metastasis. Simultaneously, PDT could induce the immune response to tumors. This novel photosensitizer could be a candidate for cancer treatment in clinical practice.

A variety of nano-engineered photosensitizers have been developed for photodynamic therapy (PDT) of cancer diseases. However, traditional nano-engineering methods usually cannot avoid drug leakage and premature release, and have disadvantages such as low drug load and inaccurate release. The self-assembly strategy based on amphiphilic peptides has been considered to be more attractive nano-engineering method. Here we developed novel acid-activatable self-assembled nanophotosensitizers based on an amphiphilic peptide derivative. The peptide derivative was synthesized from a fluorescein molecule with thermally activated delayed fluorescence (TADF). The self-assembled nanophotosensitizers can specifically enter the tumor cells and disassemble inside lysosomes companied with “turn-on” fluorescence and photodynamic therapy effect. Such smart nanophotosensitizers will open new opportunities for cancer theranostics.

PEGylation of nano‐drug delivery systems (NDDSs) has been investigated to overcome the side effect of conventional chemotherapy including improving pharmacokinetics by prolonging drug circulation, reducing immune clearance and premature drug leakage. Although, PEGylation of NDDSs can also disturb the tumor penetration and cellular uptake with the diameter enhancement. Therefore, in this work, we constitute a light‐triggered dePEGylation strategy, which results in the decrease of diameter of the pH‐responsive hydroxyapatite drug nanocarriers (DOX@HAP‐PEG) for enhanced cellular uptake and tumor penetration. Under light irradiation (650 nm), PEG chains can be availably separated from the nanocarrier by cleaving the Cy linker. Moreover, the cellular uptake of DOX@HAP‐PEG and DOX@HAP‐PEG+L (DOX@HAP‐PEG under light irradiation) are explored against MCF‐7, Hela, and HepG2 cancer cells. The results show that the cellular uptake of DOX@HAP‐PEG is lower than that of DOX@HAP‐PEG+L. In addition, in 3D tumor model, DOX@HAP‐PEG+L can better penetrate into the cell spheroid than DOX@HAP‐PEG, which is demonstrated by the accumulated fluorescence signals in the cell spheroid.

Efficiency of standard chemotherapy is dramatically hindered by intrinsic multidrug resistance (MDR). Recently, to amplify therapeutic efficacy, photodynamic therapy (PDT)-induced mitochondrial dysfunction by decorating targeting moieties on nanocarriers has obtained considerable attention. Nevertheless, low targeting efficiency, complex synthesis routes, and difficulty in releasing contents become the major obstacles in further clinical application. Herein, an ingenious liposomal-based nanomedicine (L@BP) was fabricated by encapsulating a mitochondria-anchored photosensitizer (Cy-Br) and paclitaxel (PTX) for realizing enhanced cooperation therapy. At the cellular level, L@BP could hurdle endosomal traps to localize and implement PDT in mitochondria. Intriguingly, the PDT-induced in situ mitochondrial dysfunction led to intracellular ATP reduction, which triggered the downregulated P-glycoprotein transportation capacity and thus resulted in diminishing the efflux of chemotherapeutic agents and increasing drug uptake by drug-resistant cells. The prepared nanomedicine eminently accumulated in the tumor site and acquired enhanced therapeutic efficiency on PTX-resistant lung cancer cells, which possessed great potential in circumventing MDR tumors.

Highly efficient triplet photosensitizers (PSs) have attracted increasing attention in cancer photodynamic therapy where photo-induced reactive oxygen species (ROSs, such as singlet oxygen) are produced via singlet–triplet intersystem crossing (ISC) of the excited photosensitizer to kill cancer cells. However, most PSs exhibit the fatal defect of a generally less-than-1% efficiency of ISC and low yield of ROSs, and this defect strongly impedes their clinical application. In the current work, a new strategy to enhance the ISC and high phototherapy efficiency has been developed, based on the molecular design of a thio-pentamethine cyanine dye (TCy5) as a photosensitizer. The introduction of an electron-withdrawing group at the meso-position of TCy5 could dramatically reduce the singlet–triplet energy gap (ΔEst) value (from 0.63 eV to as low as 0.14 eV), speed up the ISC process (τISC = 1.7 ps), prolong the lifetime of the triplet state (τT = 319 μs) and improve singlet oxygen (1O2) quantum yield to as high as 99%, a value much higher than those of most reported triplet PSs. Further in vitro and in vivo experiments have shown that TCy5-CHO, with its efficient 1O2 generation and good biocompatibility, causes an intense tumor ablation in mice. This provides a new strategy for designing ideal PSs for cancer photo-therapy., The electron-withdrawing group at the meso-position of Thio-Cy5 could dramatically reduce the singlet–triplet energy gap, and speed up the intersystem crossing process.

Direct-infusion nanoelectrospray ionization high-resolution mass spectrometry (DI-nESI-HRMS) is an alternative approach to chromatography-MS-based techniques for nontargeted metabolomics, offering a high sample throughout. However, its annotation accuracy of analytes is still full of challenges. In this study, we proposed a strategy for the annotation and quantitation of nontargeted metabolomic data using a spectral-stitching DI-nESI-HRMS with data-independent acquisition. The metabolite annotation strategy included the isotopic distribution, MS/MS spectrum similarity, and precursor and product ion correlation as well as matching of the extracted metabolite features along with the targeted metabolite precursors. Two groups of mixed standard solutions containing 40 and 79 metabolites were, respectively, used to establish the metabolite annotation strategy and validate its reliability. The results showed that the detected standards could be well annotated at top three explanations and total qualitative percentages were 100% (40 of 40) for the standard solution and 94.9% (74 of 78) for the standards spiked into the serum matrix. The intensity of the precursor ions was used for quantitation except for isomers, which were quantified by the intensities of the characteristic product ions if available. Finally, the strategy was applied to study serum metabolomics in diabetes, and the results demonstrated that it is promising for a large-scale cohort metabolomic study.

Photodynamic therapy (PDT) is a treatment that uses light-sensitive drugs and a light source to destroy cancer cells. Methylene blue (MB) is an efficient photosensitizing agent that has been widely used in PDT. However, MB suffers from the hypochromic effect that is caused by self-aggregation and DNA binding in vivo. It is also easily reduced to ineffective leucomethylene blue in the hypoxic environments surrounding solid tumors. In this work, we prepared MB carbon dots (MB-CDs) using MB as the carbon source. The MB-CDs not only inherit the PDT capabilities of MB, but also demonstrate good biocompatibility and low toxicity. Importantly, MB-CDs demonstrate excellent resistance to interference from reduction, aggregation, and DNA interactions. The MB-CDs exhibited satisfactory PDT activities both in vitro and in vivo. The tumor sizes were reduced to below 20% of their original volumes when irradiated by a 590-nm light-emitting diode source.

Photodynamic therapy (PDT), a light triggered therapeutic mode, has been recognized as an attractive treatment for oncotherapy. The phototoxicity to normal tissues during treatment limited the development of PDT owing to the always “on” properties of photosensitizers. Activatable photosensitizers are of great importance for improving the selectivity of PDT. Herein, we regarded the overexpressed GGT (γ-Glutamyl transpeptidase) enzyme in tumor cells as a biomarker and developed an activatable photosensitizer Cy-GGT by decorating a specific recognition moiety of GGT, L-glutamic acid, to a hemicyanine dye based on photosensitizer Cy-NH2. Cy-GGT was in the “off” state with negligible fluorescence and suppressed singlet oxygen generation, but it could be specifically hydrolyzed to Cy-NH2 in the presence of GGT, accompanied with significant fluorescence recovery and singlet oxygen generation increase under light irradiation. The in vitro and in vivo studies indicated that Cy-GGT was suitable for precise tumor imaging and could work as an efficient photosensitizer for inhibiting tumor growth.

Chemotherapy is one of the commonly used methods to treat various types of cancers in clinic by virtue of its high efficiency and universality. However, strong side effects and low concentration of conventional drugs at the tumor site have always been important factors that plague the chemotherapy effects of patients, further precluding their practical applications. Thereof, to solve the above dilemma, by integration of anticancer drug (nitrogen mustard, NM) into an NIR fluorophore (a dicyanoisophorone derivative), an intelligent prodrug NIR-NM was developed via molecular engineering strategy. Prodrug NIR-NM stimulated in hypoxia condition exhibits significantly higher toxicity to cancer cells than normal cells, essentially reducing the collateral damage to healthy cells and tissues of nitrogen mustard. More importantly, the nanoparticle prodrug FA-lip@NIR-NM showed the advantages of the high accumulation of drug at tumor site and long-circulation capacity in vivo , which endowed it the ability to track the release of the active chemotherapeutic drug and further treat solid tumors.

Singlet oxygen (1O2) is a strong oxidant which plays important roles in photodynamic therapy (PDT). The exploitation of photosensitizers with high 1O2 production is crucial to improve PDT efficiency. In this study, a radical labeled quartet photosensitizer Cy-DENT is reported with high singlet oxygen quantum yield (ΦΔ=32.3%) due to a radical enhanced inter-system crossing (ISC) process. After the introduction of 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) radical, quartet state 4[R,T] of Cy-DENT could be formed to give an over 20-fold enhancement of singlet oxygen quantum yield compared to Cy-DEN (without TEMPO radical) under irradiation of near infrared (NIR) light. In addition, the 1O2 production is well controlled by varying the electron-donating ability of the terminal substituent group. Cy-DENT possesses good cell permeability and is localized in mitochondria. Under the irradiation of 700 nm light, Cy-DENT can produce high levels of ROS to destroy the mitochondria membrane potential and induce cell apoptosis. Through the encapsulation of PEG-SS-PCL micelle, Cy-DENT can be effectively delivered to tumors and suppresses the tumor growth after PDT treatment.

Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both in vitro and in vivo experiments prove that APNB can efficiently treat A. baumannii infection. Particularly, the recovery from A. baumannii infection after APNB treatment is faster than that with ampicillin and polymyxin B in vivo. Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice.

Porous polybenzimidazole (PBI) membranes with a high ability to store phosphoric acid (PA) and transfer protons are promising materials as high-temperature proton exchange membranes (HT-PEMs) for fuel cell applications. However, porous PA-doped PBI membranes show poor mechanical properties due to porous structure and the PA plasticizing effect. Herein, a new leaf-like three-layer porous PA-doped PBI HT-PEM is designed and prepared, which contains an inside porous layer and two dense skin layers as the protected layers. Such a unique structure endows PA-doped PBI to reach a high PA-doping level, thus improving the proton exchange performance. The as-prepared three-layer HT-PEM exhibits the highest peak power density of 713 mW cm−2, superior to that of a two-layer membrane (551.1 mW cm−2). Additionally, the durability of three-layer HT-PEM fuel cells is greatly enhanced through a cross-linking method, and only 0.064 mV h−1 decay of load voltage is observed after 200 h. These results indicate that the introduction of a leaf-like three-layer porous structure is an effective strategy to design HT-PEMs with excellent performance for fuel cell applications.

Circulating tumor cells (CTCs) have been considered as a potential biomarker for evaluation of cancer metastasis and prognosis, especially in hepatocellular carcinoma (HCC). However, the isolation and detection of rare CTCs in HCC patients face enormous challenges due to omittance and nonspecific binding. We previously designed a small molecular NIR fluoresent agent, named MLP, which had high affinity with a tumor cell-overexpressed enzyme, aminopeptidase N (APN). Based on that, in this work we introduced a novel strategy via coassembling the antiepithelial cell adhesion molecule (EpCAM) antibody and MLPinto theFe3O4 magnetic nanobeads (MB-MLP-EpCAM) to isolate and identify HCC-CTCs coinstantaneously. MB-MLP-EpCAM significantly improved the CTC-capture efficiency (>85%) without sacrificing cell viability (>90%). Most importantly, the advantages of precise dual-targetability, high resolution of fluorescence imaging, and prominent selectivity make our nanoplatform have great potential to achieve in vivo real-time identification and monitoring of CTCs clinically.

Chemodynamic therapy (CDT) refers to generating hydroxyl radical ( OH) in tumor sites via hydrogen peroxide (H2O2) catalyzed by transition metal ions in cancer cells under acidic environment. However, H2O2 content is not enough for effective CDT, although H2O2 content in cancer cells is higher than that of normal cells. Herein, we synthesized DOX@BSA-Cu NPs (nanoparticles) for effective CDT by providing enhanced content of H2O2 in cancer cells. The results proved Cu2+ in NPs could be reduced to Cu+ by glutathione (GSH) and effectively converted H2O2 to OH. Moreover, the loaded low-dose doxorubicin (DOX) in the NPs could improve the content of H2O2 and resulted in more efficient generation of OH in cancer cells. Thus DOX@BSA-Cu NPs exhibited higher cytotoxicity to cancer cells. This research may provide new ideas for the further studies on more effective Cu(II)-based CDT nanoagents.

The detection of the circulating tumor cells (CTCs) detached from solid tumors has emerged as a burgeoning topic for cancer diagnosis and treatment. The conventional CTC enrichment and identification mainly rely on the specific binding of the antibodies on the capture interface of the magnetic nanoparticles with the corresponding biomarkers on the cell membranes. However, these methods could easily generate false-negative results due to the extremely low concentration of CTCs and the internal heterogeneity of the tumor cells. Herein, with the aim of selectively identifying CTCs and improving the detection accuracy in peripheral blood, we designed the fluorometric “turn on” Au nanoparticles (DHANs) with the modification of a tumor-targeted moiety, dehydroascorbic acid (DHA) and a fluorometric aptamer, which could be “switched-on” by an over-expressed intracellular protein, namely hypoxia-inducible factor-1α (HIF 1α). This novel nanoformulated detection platform demonstrated the great capacity for visualizing various CTCs in peripheral blood with significantly improved detection efficiency and sensitivity. As a result, the nanoplatform has a great potential to be further applied for CTC detection in vitro or in vivo, which holds promise for extensive CTC studies., The detection of the circulating tumor cells (CTCs) detached from solid tumors has emerged as a burgeoning topic for cancer diagnosis and treatment.

Accurate sensing of endogenous microRNAs remains a great challenge for unsatisfactory signal-to-background ratios of traditional techniques. Meanwhile, low sensitivity and insufficient specificity ...

Palladium(0) as one of the vital transition metals, is employed in numerous industries, such as drug synthesis, aerospace high-tech field and automobile industry. When the Pd(0) enter into the body, it will bind with thiol-containing amino acids, DNA, RNA, and other biomolecules damaging to human health. Thus, developing a novel tool for monitoring and imaging of Pd(0) in vivo is very urgent. In the work, based on a intramolecular charge transfer (ICT) mechanism a two-photon fluorescent probe NIPd had been designed and synthesized for the recognition Pd(0). In vitro experiments data displayed that probe NIPd exhibited a 13-fold fluorescent increase for Pd(0) in 30 min in the aqueous solution with a detection limit of 16 nmol/L. It also showed the outstanding selectivity and antijamming performance. More importantly, NIPd could be served as a two-photon fluorescent probe for real-time monitoring Pd(0) in living cells and mice.

Photodynamic cancer therapy has attracted great attention with the increasing threat of tumors, and improving its therapeutic efficacy is highly desirable. However, due to the highly efficient intersystem crossing potency to generate singlet oxygen (1O2), high-efficiency photosensitizers often suffer from weak fluorescence and excess injury to normal tissue. To overcome these obstacles, here we show a reliable self-reporting strategy for real-time monitoring of therapeutic progression. As a proof of concept, a molecular dyad is designed by connecting benzo[a]phenoselenazinium (NBSe) to rhodamine (Rh), namely Rh-NBSe, where the fluorescence of the Rh unit is initially suppressed by the fluorescence resonance energy transfer mechanism, but enabled to recover as feedback signal once the reaction with photosensitized 1O2 takes place. The observed fluorescence increases by irradiation in vitro and in vivo successfully reflect the real-time 1O2 generation speed in photodynamic therapy. In addition, the favorable therapeutic advantages of Rh-NBSe are also verified, for example, the high ΦΔ (0.8) and the low IC50 (0.2 μM, 6 J cm−2). Based on the therapeutic ability and real-time 1O2 self-reporting ability, Rh-NBSe demonstrates significant potential for self-regulating phototherapy., Photodynamic cancer therapy has attracted great attention with the increasing threat of tumors, and improving its therapeutic efficacy is highly desirable.

PEGylation of drug delivery systems (DDSs) provides a promising approach to overcome the side effect of traditional chemotherapy via the enhanced permeability and retention (EPR) effect, although it further inhibits the internalization behavior of nanocarriers. PEGylation/dePEGylation of the nanocarriers at the desired site exhibits great advantages for nanocarrier-based on-demand drug release. Here, we reported a photoinduced polyethylene glycol (PEG) deshielding nanocarrier, SiO

Singlet oxygen (1O2) plays significant physiological and pathological functions, especially in causing photodynamic stress in vivo. However, specific 1O2 monitoring is an immense challenge, owing to its short half-lives and high oxidizing ability. To address this, we engineered three photostable two-photon fluorescence probe NBs for highly efficient 1O2 monitoring based on bioinspired novel tryptophan derivatives, among which NB-MOT was the best one comprehensively. Upon being cracked with 1O2, NB-MOT rapidly (within 5 s) demonstrated a remarkable enhancement in fluorescence intensity (∼180 fold) and lifetime (∼18 fold). Taking these advantages into account, NB-MOT was applied to evaluate exogenous and endogenous 1O2 in diverse biosystems. We successfully tracked the intracellular 1O2 level during photodynamic therapy, and for the first time achieved 1O2 mapping in live cells with dual-mode imaging as well as revealed ciprofloxacin-induced photodynamic stress in mice. NB-MOT was thus believed to be of instructive significance for studying the 1O2-mediated stress in wider biological milieus.

Photodynamic therapy (PDT) has drawn significant attention as a noninvasive cancer treatment. At present, PDT applications are limited in vivo because of the short lifetime and limited diffusion distance of cytotoxic reactive oxygen species (ROS) in the cellular environment. We propose to overcome this challenge by generating limited and short-lived ROS that are localized in key organelles, particularly the nucleus, in tumor cells. We developed Se/N-doped carbon dots (Se/N-CDs) as a photosensitizer for PDT. The Se/N-CDs were shown to bind RNA selectively by digestion experiments, isothermal titration microcalorimetry, and cell dyeing with RNA probes. Se/N-CDs near the nuclear membrane produced ROS that damaged the membrane under light irradiation, permitting the entry of more Se/N-CDs and thereby improving the conversion efficiency of photosensitization. Furthermore, in vitro and in vivo experiments indicated that the Se/N-CDs could inhibit tumor growth more effectively by PDT within the nucleus.

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., A local hydrophobic cage is built up inside fluorescent silica nanoparticles for enhancing the photophysical properties of organic dyes to overcome ACQ and poor photostability in aqueous media.

The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM-ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline-malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP-recognition units. The rapid liberation of DQM-OH aggregates in the presence of ALP resulted in aggregation-induced fluorescence. The up-regulation of ALP expression in tumor cells was imaged using DQM-ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two-photon microscopy platform, providing the fluorescence-guided recognition of sub-millimeter tumorigenesis. DQM-ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.

Conventional photosensitizers (PSs) often show poor tumor retention and are rapidly cleared from the bloodstream, which is one of the key hindrances to guarantee precise and efficient photodynamic therapy (PDT) in vivo. In this work, we present a photosensitizer assembly nanosystem that sharply enhances tumor retention up to ∼10 days. The PSs are synthesized by meso-substituting anthracene onto the BODIPY scaffold (AN-BDP), which then self-assemble into stable nanoparticles (AN-BDP NPs) with amphiphilic block copolymers due to the strong intermolecular π-π interaction of anthracene. Additionally, the incorporated anthracene excites the PSs, producing singlet oxygen under red light irradiation. Although AN-BDP NPs could completely suppress regular test size tumor (∼100 mm3 ) by one-time radiation, only 12% tumour growth inhibition rate was observed in the case of large size tumor (∼350 mm3 ) under the same conditions. Due to the long time tumor retention, AN-BDP NPs allows single-dose injection and three-time light treatments, resulting in an over 90% inhibition rate, much more efficient than single-time radiation of conventional clinically used PSs including chlorin (Ce6) and porphyrin with poor tumor retention. The results reveal the importance of long tumor retention time of PSs for efficient PDT, which can accelerate the clinical development of nanophotosensitizers. This article is protected by copyright. All rights reserved.

Inkless printing based on rewritable papers has recently made great progress because it can improve the utilization rate of papers, which is of great significance for saving resources and protecting the environment. Among them, light-responsive rewritable papers (LRPs) are a hot research topic because light is clean, easily available, wavelength and intensity adjustable, and noncontacting. However, the photochromic material, as the imaging substance of LRPs, is easily affected by environmental conditions, resulting in insufficient time to read the information. In view of this, we designed and constructed an acid/base tunable diarylethene molecular system that can effectively adjust the photochromic properties by reversibly changing the electron density of the diarylethene photoreaction center through protonation and demonstrated its potential as an imaging material with a longer legible time. What makes us more satisfied is that the acidification can not only extend the legible time of carrying information but also bring a clear and stable absorption/fluorescence imaging dual mode, which can better reflect details and improve contrast. Therefore, we believe that this tunable photochromic diarylethene molecule is a potential imaging material for the development of new LRPs.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off‐target sites. A red‐light‐activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo‐photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (1O2) cleavable linker. The polymer self‐assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off‐target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces 1O2 for photodynamic therapy. Sequentially, the generated 1O2 triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual‐model release strategy creates a synergistic chemo‐photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on‐demand release of therapeutic agents in vivo., Amphiphilic metallopolymers, which have a biodegradable polycarbonate backbone that contains the photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen cleavable linker, self‐assemble into nanoparticles. The nanoparticles carry the therapeutic agents into tumor cells without drug leakage. Red light irradiation induces sequential release of the Ru complex and PTX for enhanced chemo‐photodynamic therapy.

Monitoring the tumor oxygen level when implementing photodynamic therapy (PDT) on malignant cancer has vital significance but remains challenging yet. Herein, by structurally manipulating a 2,4-dimethylpyrrole-engineered asymmetric BODIPY scaffold with different kinds, numbers, and positions of halogen atoms, we rationally designed several monochromophore-based bifunctional photosensitizers, named BDPs (BDP-I, BDP-II, and BDP-III), with self-sensitized photooxidation characteristics for accurate oxygen reporting and photodynamic tumor ablation. We show that different ways of halogen regulation allow available tuning of BDPs' oxygen-dependent ratiometric fluorescence turn-ons upon light irradiation as well as type-II PDT efficiencies before and after self-sensitized photooxidation. Encouragingly, measuring the specific ratiometric signals of the most promising BDP-II enabled the direct observation of initial oxygen concentration in both living 4T1 cells and a tumor-bearing mice model, affording an alternative way for evaluating oxygen supplementation strategies. Meanwhile, the "always on" PDT effect of BDP-II ensured efficient tumor ablation via apoptosis. Our research was thus believed to be of instructive significance for future application of oxygen-related auxiliary strategies and the design of unimolecular multifunctional PDT agents for cancer precision therapy.

A rigid hemicyanine CSZ-J and a flexible molecule ESZ-J were synthesized. In particular, the conformationally restrained CSZ-J had higher fluorescence quantum yields, longer fluorescence lifetimes and higher triplet state quantum yields. CSZ-J could generate highly cytotoxic ROS simultaneously via type I and type II processes. This will contribute to the design and development of new photosensitizers in the future.

Tumor hypoxia has proven to be the major bottleneck of photodynamic therapy (PDT) to clinical transformation. Different from traditional O2 delivery approaches, here we describe an innovative binary photodynamic O2-economizer (PDOE) tactic to reverse hypoxia-driven resistance by designing a superoxide radical (O2•-) generator targeting mitochondria respiration, termed SORgenTAM. This PDOE system is able to block intracellular O2 consumption and down-regulate HIF-1α expression, which successfully rescues cancer cells from becoming hypoxic and relieves the intrinsic hypoxia burden of tumors in vivo, thereby sparing sufficient endogenous O2 for the PDT process. Photosensitization mechanism studies demonstrate that SORgenTAM has an ideal intersystem crossing rate and triplet excited state lifetime for generating O2•- through type-I photochemistry, and the generated O2•- can further trigger a biocascade to reduce the PDT's demand for O2 in an O2-recycble manner. Furthermore, SORgenTAM also serves to activate the AMPK metabolism signaling pathway to inhibit cell repair and promote cell death. Consequently, using this two-step O2-economical strategy, under relatively low light dose irradiation, excellent therapeutic responses toward hypoxic tumors are achieved. This study offers a conceptual while practical paradigm for overcoming the pitfalls of phototherapeutics.

Endogenous gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have been demonstrated to perform significant physiological and pharmacological functions and are associated with various diseases in biological systems. In order to obtain a deeper insight into their roles and mechanisms of action, it is desirable to develop novel techniques for effectively detecting gaseous signaling molecules. Small-molecule fluorescent probes have been proven to be a powerful approach for the detection and imaging of biological messengers by virtue of their non-invasiveness, high selectivity, and real-time in situ detection capability. Based on the intrinsic properties of gaseous signaling molecules, numerous fluorescent probes have been constructed to satisfy various demands. In this perspective, we summarize the recent advances in the field of fluorescent probes for the detection of NO, CO and H2S and illustrate the design strategies and application examples of these probes. Moreover, we also emphasize the challenges and development directions of gasotransmitter-responsive fluorescent probes, hoping to provide a general implication for future research., This perspective article aims to introduce the design principles and recognition strategies of small-molecule fluorescent probes which are applied for the detection of gas signaling molecules including NO, CO and H2S in biological systems.

In this work, bovine serum albumin-based nanoparticles, BSA-ACVA-DOX NPs, were fabricated for ultrasound-driven drug release, and exhibited excellent tissue penetration. Moreover, a pulsatile release of DOX in vivo could be programmed by in vitro (i.e., remotely) switching the ultrasound on and off.

In this study, a near-infrared (NIR) theranostic photosensitizer was developed based on a heptamethine aminocyanine dye with a long-lived triplet state. This theranostic molecule can be activated by nitroreductase under mild hypoxia to be used in fluorescence imaging and highly efficient photodynamic therapy (PDT) both in 2D and 3D (spheroids) HeLa cell culture models.

Chemiluminescence, the generation of light through chemiexcitation as a result of chemical reactions, has emerged as a novel tool for bioimaging and therapy in vivo. Due to the elimination of external optical excitation, it can effectively avoid background autofluorescence existing in fluorescence techniques, providing extremely high signal-to-noise ratios and sensitivity in bioimaging. Furthermore, in situ emitted photons can replace traditional excitation light to construct chemiexcited photodynamic therapy or drug release systems for the monitoring and treatment of deeply seated diseases or tumors. In this tutorial review, we will focus on the recent advancements of chemiluminescent platforms based on luminophore substrates including luminol and its derivatives, cypridina luciferin analogs, peroxyoxalates, and dioxetanes, and systematically summarize the design principles, sensing mechanisms, and bioimaging and therapeutic applications of representative chemiluminescent probes as well as theranostic agents. Finally, the potential challenges and perspectives of chemiluminescent platforms for bioimaging and therapeutics are also discussed.