Mitochondrial H_(2)S_(n)-Mediated Anti-Inflammatory Theranostics

The insistent demand for space-controllable delivery,which reduces the side effects of non-steroidal antiinflammatory drugs(NSAIDs),has led to the development of a new theranostics-based approach for anti-inflammatory therapy.The current anti-inflammatory treatments can be improved by designing a drug delivery system responsive to the inflammatory site biomarker,hydrogen polysulfide(H_(2)S_(n)).Here,we report a noveltheranostic agent 1(TA1),consisting of three parts:H_(2)S_(n)-mediated triggering part,a two-photon fluorophore bearing mitochondria targeting unit(Rhodol-TPP),and anti-inflammatory COX inhibitor(indomethacin).In vitro experiments showed that TA1 selectively reacts with H_(2)S_(n)to concomitantly release both Rhodol-TPP and indomethacin.Confocal-microscopy imaging of inflammation-inducedlive cells suggested that TA1 is localized in the mitochondria where the H_(2)S_(n)is overexpressed.The TA1 reacted with H_(2)S_(n)in the endogenous and exogenous H_(2)S_(n)environments and in lipopolysaccharide treated inflammatory cells.Moreover,TA1 suppressed COX-2 level in the inflammatory-induced cells and prostaglandin E 2(PGE2)level in blood serum from inflammation-induced mouse models.In vivo experiments with inflammation-induced mouse models suggested that TA1 exhibits inflammation-site-elective drug release followed by significant therapeutic e ects,showing its function as a theranostic agent,capable of both anti-inflammatory therapy and precise diagnosis.Theranostic behavior of TA1 is highly applicable in vivo model therapeutics for the inflammatory disease.

Electric-field-controlled highly regioselective thiocyanation of N-containing heterocycles

Achieving highly regioselective synthesis in organic chemistry is challenging due to the uncontrollable orientation between reacting partners.External electric fields(EEFs)can influence the reactivity and selectivity of the substrate by causing directional adsorption.However,scalable and efficient techniques for using EEFs as“smart catalysts”have been lacking,hindering their application.In this study,we present a novel method for modifying the regioselectivity of quinoxaline-2(1H)-ones by functionalizing their C7-position using the electric double layer(EDL)theory.This approach led to moderate to good yields of the corresponding C7-thiocyanation products.DFT calculations and control experiments demonstrated that EEFs could reverse the regioselectivity of quinoxaline-2(1H)-ones,allowing the C7-thiocyanation to proceed via a radical reaction mechanism.Additionally,the resulting 7-thiocyano-1-methylquinoxaline-2(1H)-ones exhibited promising AIE properties.Our work showcases a promising strategy for achieving highly regioselective functionalization by aligning the electric field with the desired reaction/bond axis.

Palladium-free chemoselective probe for in vivo fluorescence imaging of carbon monoxide

Carbon monoxide(CO)is a vital intracellular gas messenger known for its cytoprotective and homeostatic properties.It plays a pivotal role in a myriad of biological processes.Therefore,the precise detection of CO is of paramount importance in unraveling the intricacies of pathological mechanisms and advancing the development of disease diagnosis.We herein introduce NFCOP,a state-of-the-art near-infrared(NIR)turn-on fluorescence(FL)probe that has been meticulously designed for highly sensitive,swift and selective imaging of CO.The NFCOP response occurred rapidly with CO,within just 10 s,and the calculated detection limit for CO was determined to be 0.32μmol/L.Further investigations conducted at the cellular level and in vivo demonstrated that NFCOP possesses high sensitivity and selectivity for imaging CO.

Lighting up plants with near-infrared fluorescence probes

Fluorescence imaging is a non-invasive and highly sensitive bioimaging technique that has shown remarkable strides in plant science. It enables real-time monitoring and analysis of biological and pathological processes in plants by labeling specific molecular or cellular structures with fluorescent probes. However, tissue scattering and phytochrome interference have been obstacles for conventional fluorescence imaging of plants in the ultraviolet and visible spectrum, resulting in unsatisfactory imaging quality. Fortunately, advances in near-infrared(NIR) fluorescence imaging technology(650-900 nm) offer superior spatial-temporal resolution and reduced tissue scattering, which is sure to improve plant imaging quality. In this review, we summarize recent progress in the development of NIR fluorescence imaging probes and their applications for in vivo plant imaging and the identification of plant-related biomolecules. We hope this review provides a new perspective for plant science research and highlights NIR fluorescence imaging as a powerful tool for analyzing plant physiology, adaptive mechanisms, and coping with environmental stress in the near future.

NIR emissive Ru(Ⅱ)metallacycle as a sonosensitizer/sonocatalyst assisting in vivo bacterial diagnosis and eradicating multidrug-resistant biofilms

Microbial biofilm-related infections present a significant global health challenge,posing a major threat to public health systems[1].Biofilms,complex structures formed by the aggregation of microorganisms,are commonly found on medical devices,human tissue surfaces,and in natural environments[2].These biofilms exhibit high levels of antibiotic resistance and survival stability,rendering traditional antibiotic treatments ineffective in eradicating infections[3].

A Plasma Membrane Polarity Sensor Harnessing Conjoined Twisted Intramolecular Charge Transfer Modulation and Charge Number Control Strategy

Polarity is a critical microenvironmental factor of the plasma membrane,which can offer valuable insights into various biological processes.Herein,we proposed a novel strategy for the construction of fluorescent agents to measure plasma membrane polarity by conjoining twisted intramolecular charge transfer(TICT)modulation and charge number control.It is shown that compounds with a stronger TICT tendency are more sensitive to polarity shifts due to the number of dialkylated amino groups present(from 1 to 3),and the molecules with two or more charged centers remain in the plasma membrane.Therefore,we developed two fluorescent agents with high polarity sensitivity,excellent turn-on ratios,and superior ability,to target the plasma membrane.In the wash-free fluorescence imaging and fluorescence lifetime tests,our designed agent could detect plasma membrane polarity with high precision,allowing effective distinction between cancer cells and normal cells based on their differences in plasma membrane polarity.Moreover,both fluorescence and fluorescence lifetime changes of the plasma membrane in the ferroptosis model established by Sorafenib confirmed an increase in plasma membrane polarity during cell ferroptosis.

Covalent organic framework nanomedicines:Biocompatibility for advanced nanocarriers and cancer theranostics applications

Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area.The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs,such as poor localization at the tumor site,high drug doses and toxicity,recurrence,and poor immune response.However,inadequate biocompatibility restricts their potential in clinical translation.Therefore,advanced nanomaterials with high biocompat-ibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines.Intrinsic properties of nanoscale covalent organic frameworks(nCOFs),such as suitable size,modular pore geometry and porosity,and straightforward post-synthetic modification via simple organic transformations,make them incredibly attractive for future nanomedicines.The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery.This review summarizes recently published applications of COFs in drug delivery,photo-immuno therapy,sonodynamic therapy,photothermal therapy,chemotherapy,pyroptosis,and combination therapy.Herein we mainly focused on modifications of COFs to enhance their biocompatibility,efficacy and potential clinical translation.This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nano-medicines and will help in the rapid development of cancer drug carriers and theranostics.

Photo-Activated Ferroptosis for Cancer Therapy: Advances, Challenges, and Prospects

Ferroptosis, a recently identified form of non-apoptotic programmed cell death, has attracted significant attention in the field of cancer therapy due to its unique mechanism of cell death. To meet the demands of ferroptosis-mediated cancer treatment, several small molecule-based drugs have been reported for the implementation of ferroptosis. However, some cancer cells are inherently resistant to these drugs, and the lack of selectivity of these drugs against cancer cells can limit their clinical application. Recent advancements in light-mediated biomedical techniques offer a promising alternative for the development of ferroptotic therapy, that is photo-controlled activation of ferroptosis. In this review, we systematically summarize the current strategies for photo-controlled ferroptosis activation and detail analysis of the underlying mechanisms of those photo-controlled ferroptotic therapies. Finally, we discuss the challenges associated with photo-activated ferroptosis and provide an outlook on the future developments in ferroptotic cancer therapy.

Construction of a 980 nm laser-activated Pt(Ⅱ)metallacycle nanosystem for efficient and safe photo-induced bacteria sterilization

Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vivo difficult.We therefore synthesized a novel Pt(Ⅱ)metallacycle(Pt1110)that can be activated with a 980 nm laser for photodiagnosis/treatment in deep tissue.We found that Pt1110 significantly improved photothermal conversion(95%improvement)and ^(1)O_(2) generation(ΦΔ75%increase)compared to the ligand itself 1 and was well capable of light-induced sterilization under safe laser irradiation(0.72 W/cm^(2)).In addition,Pt1110 has little to no toxicity to cells.After incorporated into liposome,Pt1110 NPs was effective in wound healing in infection and keratitis models upon laser irradiation,which was accurately observed by NIR-Ⅱfluorescence imaging.This novel metal-coordinated supramolecular material has a potential to become a universal platform for phototherapy in deep tissue.

Regulating the microenvironment with nanomaterials:Potential strategies to ameliorate COVID-19

COVID-19,caused by SARS-CoV-2,has resulted in serious economic and health burdens.Current treatments remain inadequate to extinguish the epidemic,and efficient therapeutic approaches for COVID-19 are urgently being sought.Interestingly,accumulating evidence suggests that microenvironmental disorder plays an important role in the progression of COVID-19 in patients.In addition,recent advances in nanomaterial technologies provide promising opportunities for alleviating the altered homeostasis induced by a viral infection,providing new insight into COVID-19 treatment.Most literature reviews focus only on certain aspects of microenvironment alterations and fail to provide a comprehensive overview of the changes in homeostasis in COVID-19 patients.To fill this gap,this review systematically discusses alterations of homeostasis in COVID-19 patients and potential mechanisms.Next,advances in nanotechnology-based strategies for promoting homeostasis restoration are summarized.Finally,we discuss the challenges and prospects of using nanomaterials for COVID-19 management.This review provides a new strategy and insights into treating COVID-19 and other diseases associated with microenvironment disorders.

NIR-Ⅱ thiopyrylium dyads guided photodynamic inactivation of coronavirus

COVID-19,a highly contagious respiratory infection caused by the SARS-Co V-2 virus,was first identified in December 2019 and has rapidly expanded to become a global pandemic[1].From then on,millions of people were infected,while the exact number of infections is difficult to determine,as not all people who are infected with the virus get tested,and some may not show any symptoms,and the number is rising as the pandemic continues.The sickness is characterized by fever,cough.

Organic functional dyes

Functional dyes go beyond traditional color applications and offer distinctive properties and functionalities,making them suitable for a wide range of industrial applications such as healthcare,agriculture,textiles,and electronics.Functional dyes can serve as fluorescent probes in medical research,photosensitizers in cancer therapy,pesticide markers in agriculture,antimicrobial agents on textiles,and charge transport materials in electronics.The ongoing research into new functional dyes reflects the interest of industries in identifying novel applications for these materials.

2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

Picomolar-sensitiveβ-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulatedπ-elongated dioxaborine-dyes

The pathological origin of Alzheimer’s disease(AD)is still shrouded in mystery,despite intensive worldwide research efforts.The selective visualization ofβ-amyloid(Aβ),the most abundant proteinaceous deposit in AD,is pivotal to reveal AD pathology.To date,several small-molecule fluorophores for Aβspecies have been developed,with increasing binding affinities.In the current work,two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ_(1-42) fibrils-while concurrently preventing poor aqueous solubility-via biannulate donor motifs in D-π-A dyes.An unprecedented sub-nanomolar affinity was found(K_(d)=0.62±0.33 nM)and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo.These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.

Fluorescent Visualization of Nucleolar G-Quadruplex RNA and Dynamics of Cytoplasm and Intranuclear Viscosity

The nucleolus,the locus of ribosome biogenesis,was found to be the predominant intracellular target of a new fluorescent probe,V-P1.In solution,the probe demonstrated both a selectivity to RNA G-quadruplexes and a sensitivity to the viscosity,while G-quadruplex binding did not disturb the viscosity sensing.In cells,confocal and fluorescence lifetime imaging,combined with digestion and competition experiments,lent support to the hypothesis of an RNA-based G-quadruplex as the intracellular target,postulated to be nucleolar ribosomal RNA(rRNA).The probe demonstrated a high sensitivity to viscosity in both the cytoplasm and the nuclear compartment and was used to precisely interrogate the viscosity changes resulting from diverse stimuli,such as temperature,monensin treatment,and etoposide-induced apoptosis.Owing to the putative rRNA G-quadruplex binding in vitro and in vivo,and further combined with a relatively low degree of toxicity,the dye enabled the interrogation of cytoplasm and intranuclear viscosity changes under diverse conditions and found applications in studying the influence and significance of cytoplasm and intranuclear viscosity as well as in gaining insight into the native secondary structure of rRNA in nucleoli.

Ultrasound activatable antiangiogenic sonosensitizer for VEGFR associated glioblastoma tumor models

Angiogenic signaling pathway is a major contributing factor in cancer recurrence and progression,which can cause significantly reduced treatment outcomes,especially in the oxygen-dependent photo-and sonodynamic therapies.VEGF and its receptor(VEGFR)play a crucial role in angiogenesis progression;precisely,upregulated VEGF signaling ismainly associated with angiogenesis progression in many types of cancers.Herein,we report a sunitinib-conjugated sonosensitizer(TK-RB:tyrosine kinase-rose bengal)to enhance the anticancer efficacy through VEGF inhibitionmediated antiangiogenesis in conjunction with cellular/tumor damage by ROS generated under ultrasound irradiation.TK-RB reveals good selectivity and cytotoxicity toward VEGFR-positive cells(U87MG)over VEGFR-negative cells(MCF-7).The fluorescent imaging analysis in vivo/ex vivo and the tumor growth investigation in nude mice with U87MG glioblastoma tumor xenografts demonstrate that rose bengal having tyrosine kinase inhibitor(TK-RB)provides an enhanced antitumor effect.The current strategy will make a great contribution to optimizing anticancer performance by utilizing sonodynamic therapy together with antiangiogenics in several different malignancies.