Photonic control of ligand nanospacing in self-assembly regulates stem cell fate

Extracellular matrix(ECM)undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored.Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo^(+)self-assembly composed of azobenzene derivatives(Azo^(+))stacked via cation-πinteractions and stabilized with RGD ligand-bearing poly(acrylic acid).Near-infrared-upconverted-ultraviolet light induces cis-Azo^(+)-mediated inflation that suppresses cation-πinteractions,thereby inflating liganded self-assembly.This inflation increases nanospacing of“closely nanospaced”ligands from 1.8 nm to 2.6 nm and the surface area of liganded selfassembly that facilitate stem cell adhesion,mechanosensing,and differentiation both in vitro and in vivo,including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo^(+)molecules and loaded molecules.Conversely,visible light induces trans-Azo^(+)formation that facilitates cation-πinteractions,thereby deflating self-assembly with“closely nanospaced”ligands that inhibits stem cell adhesion,mechanosensing,and differentiation.In stark contrast,when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly,the surface area of“distantly nanospaced”ligands increases,thereby suppressing stem cell adhesion,mechanosensing,and differentiation.Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified.This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging

Phototherapeutic nanoplatforms that combine photodynamic therapy(PDT)and photothermal therapy(PTT)with the guidance of photoacoustic(PA)imaging are an effective strategy for the treatment of tumors,but establishing a universal method for this strategy has been challenging.In this study,we present a supramolecular assem-bly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent(PcDA)via the anion and cation supramolec-ular interaction between two water-soluble phthalocyanine ramifications,PcD and PcA.This approach promotes the absorption of energy,thus enhancing the genera-tion of reactive oxygen species(ROS)and heat by PcDA,improving its therapeutic efficacy,and overcoming the low photon utilization efficiency of conventional PSs.Notably,after the intravenous injection of PcDA,neoplastic sites could be clearly visualized using PA imaging,with a PA signal-to-liver ratio as high as 11.9.Due to these unique features,PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light irradiation.This study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging.

Fluorescent probes for the detection of disease-associated biomarkers

Fluorescent probes have emerged as indispensable chemical tools to the field of chemical biology and medicine.The ability to detect intracellular species and monitor physiological processes has not only advanced our knowledge in biology but has provided new approaches towards disease diagnosis.In this review,we detail the design criteria and strategies for some recently reported fluorescent probes that can detect a wide range of biologically important species in cells and in vivo.In doing so,we highlight the importance of each biological species and their role in biological systems and for disease progression.We then discuss the current problems and challenges of existing technologies and provide our perspective on the future directions of the research area.Overall,we hope this review will provide inspiration for researchers and prove as useful guide for the development of the next generation of fluorescent probes.

Photodynamic and photothermal therapies for bacterial infection treatment

Bacteria can cause numerous infectious diseases and has been a major threat to human humans.Although antibiotics have partially succeeded in treating bacteria,owing to antibiotic abuse,the emergence of multidrug-resistant(MDR)bacteria has drastically diminished their potency.Since the invention of laser,the combination of light and photosensitizers,photodynamic therapy(PDT),has become an effective noninvasive treatment along with photothermal therapy(PTT),in which heat is generated by nonradiative relaxation.Antimicrobial PDT and PTT are emerging as effective treatments for bacterial infection,particularly against MDR bacteria.This mini review covers the recent progresses in PDT and PTT for bacterial treatment.

A bifunctional rhodamine derivative as chemosensor for recognizing Cu^2+ and Hg^2+ ions via different spectra

A new simple bifunctional chemosensor 1 based on rhodamine was synthesized by hydrazide and formylformic acid,which could detect Cu^2+and Hg^2+via dif ferent detecting methods in CH3 CN-HEPES buffer solution(20 mmol/L,pH 7.4)(1:9,v/v)respectively.When sensor 1 bound with Cu^2+,it showed a colorimetric change,while a selective enhancement in fluorescence occurred upon 1 binding with Hg^2+,resulting from the spirolatam-ring opening process.The binding modes of 1 with Cu^2+and Hg^2+were investigated based on UV,fluorescence change,ESI-Mass and Job’s Plot data.Moreover,sensor 1 could selectively detect target ion in a mixed solution of Cu^2+and Hg^2+,and the two metal ions do not inte rfere with each other in the process of detecting Cu^2+or Hg^2+with 1.

Rational Design and Application of an Indolium-Derived Heptamethine Cyanine with Record-Long Second Near-Infrared Emission

Heptamethine cyanine dyes,typified by indocyanine green,have been extensively employed as bioimaging indicators and theranostic agents.Significant efforts have been made to develop functional heptamethine cyanine dyes with outstanding bioimaging and theranostic utilities.In this work,we rationally designed and successfully developed a novel indolium-like heptamethine cyanine dye by installing indolium-derived polycyclic aromatic hydrocarbons on the terminal ends of a conjugated polyene backbone.This dye showed excellent photostability and showed bright fluorescent emission in the second near-infrared(NIR-Ⅱ)window with a peak at approximately 1120 nm.Such long wavelength emission prompted a superior bioimaging resolution in vivo.In particular,this NIR-Ⅱ dye had the remarkable capability of marking the blood vessels of the hindlimbs,abdomens,and brains of mice.More significantly,this dye involved a typical indolium-like heptamethine skeleton and exhibited two strong absorption bands in the 700–1300 nm NIR range,which endowed it with an intrinsic tumor-targeting capability and a high photothermal conversion efficiency(up to 68.2%),serving for the photothermal therapy of tumors under the guidance of NIR-Ⅱ fluorescence imaging.This work provides an efficient design strategy for achieving indolium-like heptamethine cyanine dyes with further NIR-Ⅱ emission.

Molecular Structural Evolution of Near-Infrared Cationic AggregationInduced Emission Luminogens:Preclinical Antimicrobial Pathogens Activities and Tissues Regeneration

Increasingly infectious diseases from microbial pathogens(including bacteria and fungi)threaten human health:a situation that has aroused public health concern around the world.Unfortunately,broad-spectrum antimicrobial agents for treatment resistance pathogens and molecular research on their antimicrobial mechanisms are still scarce.Thus,the development of smart agents against microbial infection for surmounting the above dilemmas is an urgent task.In this contribution,we have tactfully designed a family of flexible aggregation-induced emission luminogens(AIEgens)with various alkyl chain lengths and successfully optimized a cationic AIEgen TPA-S-C6-NMe_(3)^(+)based on the molecular relay strategy for killing both bacteria and fungi in vitro with desired results under white light irradiation,superior to traditional commercial photosensitizers including methylene blue,chlorin e6,and protoporphyrin IX.The cationic AIEgen TPA-S-C6-NMe_(3)^(+)was bound to microbial pathogens via electrostatic and hydrophobic forces and exerted antimicrobial efficacy due to the synergistic effect of alkyl chain length,reactive oxygen species(ROS)generation capability,and two positive charges.Remarkably,AIEgen TPA-S-C6-NMe_(3)^(+)also exhibited a striking antimicrobial activity in vivo,and promoted the generation of new blood vessels and fibroblasts in bacteria-infected tissues,which was beneficial for wound healing in mice.Overall,we expect that our work could provide a powerful tool against microbial pathogens to avoid infections and to promote tissues regeneration in clinical practice.

Turning an FDA-approved therapeutic into an AIEgen for imaging live bacteria and for bacterial detection

Aggregation Induced Emission(AIE)is an attractive,fluorescent-based phenomenon that can be used to design fluorescent imaging agents and fluorescent sensors.In this highlight,we discuss a recently reported study that identifies the chemical scaffold of an FDA-approved therapeutic(deferasirox)as a molecule with AIE-like properties(AIEgen).Utilizing its therapeutic efficacy for bacterial biofilms,deferasiroxderivatives were shown able to treat and image bacteria biofilms and detect a bacterial biomarker.This demonstrates the potential of AIE for drug design as this allows the simultaneous ability to image the therapeutic’s location and mode of action.

Hypoxia-activatable nano-prodrug for fluorescently tracking drug release in mice

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.

Activity-based smart AIEgens for detection,bioimaging,and therapeutics:Recent progress and outlook

Activity-based approaches for designing AIEgens possess prominent advantages including high selectivity,sensitivity,and signal-to-noise ratio,and they have received more attention in recent years.Excellent activatable AIE probes have been reported for detecting toxic substances,imaging intracellular active molecules/biomolecules,as well as monitoring the activity of overexpressed enzymes in cancers.Moreover,the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation,while they have no distinct effect on normal cells,demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy.Thus,in this review,we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications.The challenges of activatable AIE probes and the corresponding solutions are described.We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.