A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-Ⅱ Photo-Immunotherapy of Metastatic Tumor

Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.

Design and optimization of a greener sinomenine hydrochloride preparation process considering variations among different batches of the medicinal herb

The current methods used to industrially produce sinomenine hydrochloride involve several issues,including high solvent toxicity,long process flow,and low atomic utilization efficiency,and the greenness scores of the processes are below 65 points.To solve these problems,a new process using anisole as the extractant was proposed.Anisole exhibits high selectivity for sinomenine and can be connected to the subsequent water-washing steps.After alkalization of the medicinal material,heating extraction,water washing,and acidification crystallization were carried out.The process was modeled and optimized.The design space was constructed.The recommended operating ranges for the critical process parameters were 3.0–4.0 h for alkalization time,60.0–80.0℃ for extraction temperature,2.0–3.0(volume ratio)for washing solution amount,and 2.0–2.4 mol·L^(-1) for hydrochloric acid concentration.The new process shows good robustness because different batches of medicinal materials did not greatly impact crystal purity or sinomenine transfer rate.The sinomenine transfer rate was about 20%higher than that of industrial processes.The greenness score increased to 90 points since the novel process proposed in this research solves the problems of long process flow,high solvent toxicity,and poor atomic economy,better aligning with the concept of green chemistry.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

BACE1 inhibitors:A promising therapeutic approach for the management of Alzheimer’s disease

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta(Aβ)aggregates,resulting from mutations in the amyloid precursor protein.The enzymeβ-secretase,also known asβ-site amyloid precursor protein cleaving enzyme 1(BACE1),plays a crucial role in generating Aβpeptides.With no targeted therapy available for Alzheimer’s disease,inhibiting BACE1 aspartic protease has emerged as a primary treatment target.Since 1999,compounds demonstrating potential binding to the BACE1 receptor have advanced to human trials.Structural optimization of synthetically derived compounds,coupled with computational approaches,has offered valuable insights for developing highly selective leads with drug-like properties.This review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease agents.It summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status,indicating future directions for novel BACE1 inhibitors.The promising clinical results of Elenbecestat(E-2609)catalyze the development of effective,selective BACE1 inhibitors in the future.

The role of reactive oxygen species in gastric cancer

Gastric cancer(GC)ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide.Reactive oxygen species(ROS)are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance.ROS are closely associated with the occurrence,development,and treatment of GC.This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction.In addition,the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized.The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC.

Biological,pathological,and multifaceted therapeutic functions of exosomes to target cancer

Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.

Veratrilla baillonii Franch alleviate the symptoms of diabetes in type 2 diabetic rats induced by high-fat diet and streptozotocin

Our previous research studies have shown that Veratrilla baillonii Franch,a food supplement used by ethnic minorities in Southwest China,has multiple pharmacological activities,such as detoxification,antiinflammatory,antioxidant,and anti-insulin resistance.However,the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus(T2DM)remains unclear.The current study is to evaluate the therapeutic effects of V.baillonii on T2DM rats and to explore the underlying mechanisms.The T2DM rat model was successfully established by a high-sugar and high-fat diet(HFD)combination with intraperitoneal injection of a small dose of streptozotocin(STZ,35 mg/kg).Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of V.baillonii(WVBF).The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance,ameliorate the liver,kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α,and oxidative damages.Further investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK pathways.These findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

A perspective review on the biosynthesis of plant-based secondary metabolites and their application as potent drugs

Many phytochemicals and their derived metabolites produced by plants are extensively employed in commercial goods,pharmaceutical products as well as in the environmental and medicalfields.However,these secondary metabolites obtained from plants are in low amounts,and it is difficult to synthesize them at the industrial level.Despite these challenges,they may be utilized for a variety of medicinal products that are either available in the market or are being researched and tested.Secondary metabolites are complex compounds that exhibit chirality.Further,under controlled conditions with elicitors,desired secondary metabolites may be produced from plant cell cultures.This review emphasizes the various aspects of secondary metabolites including their types,synthesis,and applications as medicinal products.The article aims to promote the use of plant secondary metabolites in the management and treatment of various diseases.

Efficacy and safety of acupuncture in treating low back and pelvic girdle pain during pregnancy:a systematic review and meta-analysis of randomized controlled trials

Objectives:Low back and pelvic girdle pain(LBPGP)is common during pregnancy.Acupuncture is an effective and safe therapy for pain relief.However,further evidence is required to confirm the efficacy and safety of acupuncture in treating LBPGP during pregnancy.This study aimed to systematically review and investigate the clinical efficacy and safety of acupuncture for the treatment of pregnancy-related LBPGP.Methods:The PubMed,EMBASE,Cochrane Library,CNKI,VIP,and WanFang databases were searched from January 2000 to August 2023.Only the randomized controlled trials(RCTs)involving pregnant women between 16 and 34 weeks of gestation diagnosed with LBPGP were included in the study.A meta-analysis was conducted and pooled risk ratios(RRs)or mean differences(MDs)with 95%confidence intervals(CIs)were compared.Results:Meta-analysis included 12 RCTs involving 1,641 participants.Eleven trials compared acupuncture alone or acupuncture combined with standard care(SC),of which three trials also used non-penetrating or placebo acupuncture as the control group.One trial compared acupuncture alone with non-penetrating acupuncture.Compared with SC,acupuncture combined with SC group significantly decreased visual analog scale score(mean difference(MD)=−2.83,95%CI=−3.41 to−2.26,P<0.00001),cesarean section rate(RR=0.69,95%CI=0.49–0.97,P=0.03),preterm birth rate(RR=0.42,95%CI=0.27–0.65,P<0.0001),labor duration(MD=−1.97,95%CI=−2.73 to−1.20,P<0.0001),and Oswestry disability index score(MD=−9.14,95%CI=−15.68 to−2.42,P=0.008).In addition,acupuncture combined with SC significantly improved 12-Items Short Form Health Survey of physical component summaries(SF12-PCS).No significant differences were observed in the spontaneous delivery rate,newborn weight,drowsiness,and 12-Items Short Form Health Survey of mental component summaries(SF12-MCS)between the two groups.Adverse events such as needle pain and needle bleeding were aggravated in both the SC and acupuncture treatment groups but none were associated with acupuncture during or after the treatment period.Conclusions:Meta-analysis showed that acupuncture combined with SC had better efficacy than SC alone and could be a potential therapy for LBPGP during pregnancy.The safety results imply that acupuncture caused few adverse reactions;however,more evidence is required for further confirmation.

Guidelines for application of high-content screening in traditional Chinese medicine:concept,equipment,and troubleshooting

High-content screening(HCS)technology combines automated high-speed imaging hardware and single-cell quantitative analysis.It can greatly accelerate data acquisition in cellular fluorescence imaging and is a powerful research technique in traditional Chinese medicine(TCM).An increasing number of laboratories and platforms,including TCM laboratories,have begun utilizing HCS systems.However,this technology is still in its infancy in TCM research and there is a lack of sufficient experience with the associated concepts,instrument configurations,and analysis methods.To improve the understanding of HCS among researchers in the field of TCM,this paper summarizes the concept of HCS,software and hardware configuration,the overall research process,as well as common problems and related solutions of HCS in TCM research based on our team’s previous research experience,providing several research examples and an outlook on future perspectives,aiming to provide a technical guide for HCS in TCM research.

Current developments of bioanalytical sample preparation techniques in pharmaceuticals

Sample preparation is considered as the bottleneck step in bioanalysis because each biological matrix has its own unique challenges and complexity.Competent sample preparation to extract the desired analytes and remove redundant components is a crucial step in each bioanalytical approach.The matrix effect is a key hurdle in bioanalytical sample preparation,which has gained extensive consideration.Novel sample preparation techniques have advantages over classical techniques in terms of accuracy,automation,ease of sample preparation,storage,and shipment and have become increasingly popular over the past decade.Our objective is to provide a broad outline of current developments in various bioanalytical sample preparation techniques in chromatographic and spectroscopic examinations.In addition,how these techniques have gained considerable attention over the past decade in bioanalytical research is mentioned with preferred examples.Modern trends in bioanalytical sample preparation techniques,including sorbent-based microextraction techniques,are primarily emphasized.

Recent advancement of chemical imaging in pharmaceutical quality control:From final product testing to industrial utilization

Chemical imaging(CI)possesses a strong ability of pharmaceutical analysis.Its great strength relies on the integration of traditional spectroscopy(one dimension)and imaging technique(two dimensions)to generate three-dimensional data hypercubes.Data pre-processing or processing methods are proposed to analyze vast data matrixes and thereby realizing different research objectives.In this review paper,various pharmaceutical applications of quality control over the past few years are summed up in two groups of final product test and industrial utilization.The scope of"quality control"here includes traditional analytical use,process understanding and manufactural control.Finally,two major challenges about undesirable sample geometry and lengthy acquisition time are discussed for prospective commercial or industrial application.

Multimodal Identification by Transcriptomics and Multiscale Bioassays of Active Components in Xuanfeibaidu Formula to Suppress Macrophage-Mediated Immune Response

Xuanfeibaidu Formula (XFBD) is a Chinese medicine used in the clinical treatment of coronavirus disease 2019 (COVID-19) patients. Although XFBD has exhibited significant therapeutic efficacy in clinical practice, its underlying pharmacological mechanism remains unclear. Here, we combine a comprehensive research approach that includes network pharmacology, transcriptomics, and bioassays in multiple model systems to investigate the pharmacological mechanism of XFBD and its bioactive substances. High-resolution mass spectrometry was combined with molecular networking to profile the major active substances in XFBD. A total of 104 compounds were identified or tentatively characterized, including flavonoids, terpenes, carboxylic acids, and other types of constituents. Based on the chemical composition of XFBD, a network pharmacology-based analysis identified inflammation-related pathways as primary targets. Thus, we examined the anti-inflammation activity of XFBD in a lipopolysaccharide-induced acute inflammation mice model. XFBD significantly alleviated pulmonary inflammation and decreased the level of serum proinflammatory cytokines. Transcriptomic profiling suggested that genes related to macrophage function were differently expressed after XFBD treatment. Consequently, the effects of XFBD on macrophage activation and mobilization were investigated in a macrophage cell line and a zebrafish wounding model. XFBD exerts strong inhibitory effects on both macrophage activation and migration. Moreover, through multimodal screening, we further identified the major components and compounds from the different herbs of XFBD that mediate its anti-inflammation function. Active components from XFBD, including Polygoni cuspidati Rhizoma, Phragmitis Rhizoma, and Citri grandis Exocarpium rubrum, were then found to strongly downregulate macrophage activation, and polydatin, isoliquiritin, and acteoside were identified as active compounds. Components of Artemisiae annuae Herba and Ephedrae Herba were found to substantially inhibit endogenous macrophage migration, while the presence of ephedrine, atractylenolide I, and kaempferol was attributed to these effects. In summary, our study explores the pharmacological mechanism and effective components of XFBD in inflammation regulation via multimodal approaches, and thereby provides a biological illustration of the clinical efficacy of XFBD.

Design and optimization of purification process of sinomenine hydrochloride

Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material.The process included the following steps: alkalization, extraction, water washing, acid–water stripping,drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively.The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.

In vivo recognition of bioactive substances of Polygonum multiflorum for protecting mitochondria against metabolic dysfunction-associated fatty liver disease

BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is a severe threat to human health.Polygonum multiflorum(PM)has been proven to remedy mitochondria and relieve MAFLD,but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear.AIM To research the active ingredients of PM adjusting mitochondria to relieve highfat diet(HFD)-induced MAFLD in rats.METHODS Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms.The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats(mitochondrial pharmacology).PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry(mitochondrial pharmacochemistry).The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model,respectively.RESULTS PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD.PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis.Eight chemicals were found in the liver mitochondria of PM-administrated rats.The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated.CONCLUSION PM restored mitochondrial structure and function and alleviated MAFLD,which may be associated with the remedy of oxidative stress and energy production.The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD.Thus,PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction.Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol,compared to 95.8% in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Efficient,rapid and incremental extraction of bioactive compounds from the flowers of Hibiscus manihot L.

Flavonoids are the primary functional components in the flowers of Hibiscus manihot L.(HMLF).In this study,an efficient and green ionic liquid-high-speed homogenization coupled with microwave-assisted extraction(IL-HSH-MAE)technique was firstly established and implemented to extract seven target flavonoids from HMLF.Single-factor experiments and Box-Behnken design(BBD)were utilized to maximize the extraction conditions of IL-HSH-MAE,which were as follows:0.1 M of[C4mim]Br,homogenate speed of 7,000 rpm,homogenate time of 120 s,liquid/solid ratio of 24 mL/g,extraction temperature of 62℃and extraction time of 15 min.The maximal total extraction yield of seven target flavonoids attained 22.04 mg/g,which was considerably greater than the yields obtained by IL-HSH,IL-MAE,60%ethanol-HSH-MAE and 60%ethanol-MAE.These findings suggested that the IL-HSH-MAE method can be exploited as a rapid and efficient approach for extracting natural products from plants.The process also possesses outstanding superiority in being environmentally friendly and having a high extraction efficiency and is expected to be a luciferous prospect extraction technology.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mitochondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HGþ6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mitochondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upregulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Treatment of colorectal cancer by anticancer and antibacterial effects of hemiprotonic phenanthroline-phenanthroline^(+) with nanomicelle delivery

Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.