Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application

Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.

Application of Nano-Delivery Systems in Lymph Nodes for Tumor Immunotherapy

Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),etc.The unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune cells.LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses.Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein.Meanwhile,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly.Therefore,LNs have become a key target for tumor immunotherapy.Unfortunately,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor effects.The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs.Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to LNs.Herein,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly.Moreover,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.

Study on the secondary structure and hydration effect of human serum albumin under acidic pH and ethanol perturbation with IR/NIR spectroscopy

Human serum albumin(HSA)is the most abundant protein in plasma and plays an essential physiological role in the human body.Ethanol precipitation is the most widely used way to obtain HSA,and pH and ethanol are crucial factors affecting the process.In this study,infrared(IR)spectroscopy and near-infrared(NIR)spectroscopy in combination with chemometrics were used to investigate the changes in the secondary structure and hydration of HSA at acidic pH(5.6-3.2)and isoelectric pH when ethanol concentration was varied from 0%to 40%as a perturbation.IR spectroscopy combined with the two-dimensional correlation spectroscopy(2DCOS)analysis for acid pH system proved that the secondary structure of HSA changed significantly when pH was around 4.5.What's more,the IR spectroscopy and 2DCOS analysis showed different secondary structure forms under different ethanol concentrations at the isoelectric pH.For the hydration effect analysis,NIR spectroscopy combined with the McCabe-Fisher method and aquaphotomics showed that the free hydrogen-bonded water fluctuates dynamically,with ethanol at 0-20%enhancing the hydrogen-bonded water clusters,while weak hydrogen-bonded water clusters were formed when the ethanol concentration increased continuously from 20%to 30%.These measurements provide new insights into the structural changes and changes in the hydration behavior of HSA,revealing the dynamic process of protein purification,and providing a theoretical basis for the selection of HSA alcoholic precipitation process parameters,as well as for further studies of complex biological systems.

Exploring the mechanism of action of DHI on myeloproliferative neoplasms based on network pharmacology

Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.

Deciphering the potential mechanism of Radix Rehmanniae Praeparata for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Rehmanniae Radix Praeparata(RRP,Shu Dihuang in Cinese)is a traditional Chinese herb with multiple pharmacological effects and is commonly used to treat blood deficiency syndrome,such as cancer-related anemia(CRA),alone or in combination with other herbs.However,its main active ingredients and mechanisms of action in treating CRA remain unknown.This study aims to elucidate RRP’s potential mechanism and main active components in treating CRA by using network pharmacology and molecular docking technology system.Methods:The main components of RRP were obtained by the TCMSP database and literature search,and active components and potential targets were obtained by the SwissADME and SwissTargetPridiction databases.CRA targets were collected through GeneCards,DisGeNET,and DrugBank databases.Protein-protein interaction networks of potential targets were constructed via STRING 11.5 and analyzed visually with Cytoscape 3.9.1.The Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis,which were subsequently visualized with Cytoscape 3.9.1 or SangerBox platform.Moreover,Autodock Vina was used for the molecular docking of potential targets and main active ingredients that were visualized with PyMOL software.Results:In this study,31 main active ingredients of PPR were screened,and 155 related targets related to CRA were unearthed.Protein-protein interaction results showed that PPR’s core proteins for CRA intervention correlate to STAT3,SRC,MAPK3,MAPK1,PIK3R1,PIK3CA,and AKT.Multiple signaling pathways were closely related to the treatment of CRA intervened by PPR,including the PI3K-Akt signaling pathway,HIF-1 signaling pathway,JAK-STAT3 signaling pathway,TNF-αsignaling,cytokine signaling pathway and NF-kappB signaling pathway,which are closely involved in the proliferation and differentiation of hematopoietic stem cell and inflammatory response.Molecular docking results showed that these potential targets had good conformation with the core active components of RRP for treating CRA.Conclusion:This study revealed RRP’s main active components and potential molecular mechanisms in treating CRA,providing a reference for subsequent basic research.

Determination of the immunoglobulin G precipitation end-point by an intelligent near-infrared spectroscopy system

Precipitation is a key manufacturing unit during the immunoglobulin G(IgG)production,which guarantees the quality of the final product.Ethanol is usually used to purify IgG during the precipitation process,so it is important to monitor the ethanol concentration online.Near-infrared(NIR)spectroscopy is a powerful process analytical technology(PAT)which has been proved to be feasible to determine the ethanol concentration during the precipitation process.However,the NIR model is usually established based on the specific process,so a universal model is needed.And the clarity degree of solution will affect the quality of the spectra.Therefore,in this study an integrated NIR system was introduced to establish a universal NIR model which could predict the ethanol concentration online and determine the end-point of the whole process.First,a spectra acquisition device was designed and established in order to get high-quality NIR spectra.Then,a simple prepared ethanol NIR model was constructed to predict the actual manufacturing process.Finally,the end-point was determined to stop the peristaltic pump when the ethanol concentration reached 20%.The results showed that the spectra quality was good,model prediction was accurate,and process monitoring was accurate.In conclusion,all results indicated that the integrated NIR system could be used to monitor the biopharmaceutical process to help us understand the pharmaceutical process.

Chemical constituents and theiranti-infective activity of Paeonia suffruticosa

Objective:Research the chemical constituents of Paeonia suffruticosa that are responsible for its anti-infective properties.Methods:Several column chromatographic methods were used to purify the chemical constituents from P.suffruticosa,including medium pressure liquid chromatography,Sephadex LH-20,and normal silica gel.A disc diffusion method was used to screen for antibacterial activity,and their anti-virulence activity was assessed on the type III secretion system(T3SS)of Salmonella pathogenicity island 1(SPI-1)in Salmonella enterica serovar Typhimurium UK-1 g 8956 by SDS-PAGE and western blots.Results:Twenty-one compounds were identified.Compounds 7,8 and 17 showed moderate activity against S.aureus ATCC25923,compounds 8,9 and 10 showed weak activities against B.subtilis ACCC11060.Meanwhile,phenols(14-18)and flavonoids(20 and 21)inhibited T3SS protein secretion of S.typhimurium without affecting bacterial growth.Furthermore,a strong inhibitory effect was observed for 17 and 20 on SPI-1 mediated invasion of HeLa cells.Additionally,no toxicity was observed for these compounds.Conclusion:P.suffruticosa has anti-infective properties due in part to the fact that phenols and flavonoids can block the secretion of T3SS-associated protein effectors.

A review of the ethnobotanical value,phytochemistry,and pharmacology of Physalis pubescens L.

Physalis pubescens L.(P.pubescens)was widely used for the treatment of inflammation-related diseases,such as sore throat,aphonia,phlegm,heat,and cough in folk medicine.The fruits of P.pubescens are commonly consumed as fruit in many areas of the world.In the past few decades,the phytochemistry and pharmacology of P.pubescens were extensively investigated.About 170 chemical constituents were purified from P.pubescens.The extract and chemical constituents of P.pubescens demonstrate diverse pharmacological effects,including anti-oxidation,anti-inflammation,anticancer,antimicrobial activity,immunomodulation,diuretic effect,hypoglycemic,and hypolipidemic in vitro and in vivo.Herein,we systematically summarized the ethnomedicinal uses,botanical characterization,distribution,phytochemistry,and pharmacology of P.pubescens,and establish the correlation between chemical constituents and pharmacological effects.

Advances in the therapeutic drugs of Coronavirus disease 2019 (COVID-19)

Since December 2019,the outbreak of a new coronavirus that named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and caused coronavirus disease 2019(COVID-19)has greatly threatened the public health and raised great concerns worldwide.In late December 2019,patients with COVID-19 were found in Wuhan,China.COVID-19 is an acute disease that causes the lesions in the lungs mainly,which develop into diffuse alveolar injury and pulmonary hyaline membrane formation to cause progressive respiratory failure in critically ill patients.Although specific drug therapies and vaccines have yet to be discovered,There're currently multiple medicines for the treatment of COVID-19 in the clinic.We have summarized the drugs widely used in the world,including remdesivir,chloroquine,favipiravir,lopinavir/ritonavir,ribavirin,some clinically adjuvant drugs and traditional Chinese medicines with great potential.In order to avoid the damage caused by immune disorders in COVID-19 patients,tocilizumab and dexamethasone plays an auxiliary role in fighting the epidemic.In this review,the potential effective drugs for COVID-19 will be summarized.

Network pharmacology prediction and molecular docking-based strategy to investigate the possibility of CPL against myeloproliferative neoplasms

Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays important roles in the pathogenesis of myeloproliferative neoplasms(MPN).This study aims to preliminarily clarify the therapeutic potential and molecular mechanisms of CPL for MPN based on network pharmacology and molecular docking techniques.Methods:The active components and corresponding action targets of CPL were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while MPN-related targets were searched through GeneCards,DisGeNET,OMIM,DrugBank and TTD databases respectively.Protein-Protein Interaction(PPI)Networks of potential targets were constructed using STRING 11.5 and analyzed visually with Cytoscape 3.9.1.In addition,Metascape platform was used for GO and KEGG analysis that were subsequently visualized with Cytoscape 3.9.1 built-in plug-ins CluoGO or SangerBox platform.Finally,Autodock Vina was used for molecular docking of potential targets and main active ingredients,which were visualized with Pymol software.Experimentally,we used in vitro mouse primary cells culture system to evaluate the effect of CPL on the erythroid and megakaryocytes differentiation that are excessively driven in MPN respectively.Results:The active components of CPL in the treatment of MPN are mainly flavonoids.The core proteins of CPL for MPN intervention are correlated to TP53,AKT1,JUN,CASP3,EGFR,TNF,MYC,IL6.Multiple signaling pathways were closely related to the treatment of MPN intervened by CPL,including PI3K-Akt signaling,TNF-αsignaling,JAK-STAT signaling and NF-κB signaling pathways.These potential targets had good conformation with the core active ingredients of CPL.In line with above findings,we demonstrated that CPL significantly inhibits the proliferation of differentiation of erythrocytes and megakaryocytes in vitro,further supporting the therapeutic potential of CPL for MPN.Conclusion:This study revealed the active ingredients and potential molecular mechanism of CPL in the treatment of MPN,providing a reference for subsequent basic research.

Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle.The covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use.Effective antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable druggability.Numerous non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available information.Prospective viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.

Discovery of GluN2A subtype-selective N-methyl-d-aspartate(NMDA)receptor ligands

The N-methyl-d-aspartate(NMDA)receptors,which belong to the ionotropic Glutamate receptors,constitute a family of ligand-gated ion channels.Within the various subtypes of NMDA receptors,the GluN1/2A subtype plays a significant role in central nervous system(CNS)disorders.The present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors,encompassing negative allosteric modulators(NAMs),positive allosteric modulators(PAMs)and competitive antagonists.Moreover,the ligands’structure–activity relationships(SARs)and the binding models of representative ligands are also discussed,providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

Design,synthesis,and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs

Inspired by our previous studies to discover novel human immunodeficiency virus-1(HIV-1)nonnucleoside reverse transcriptase inhibitors(NNRTIs)by targeting the tolerant region II of the NNRTIs binding pocket(NNIBP),a series of novel benzo[4,5]thieno[2,3-d]pyrimidine derivatives were designed through structure-based drug design as novel potent HIV-1 NNRTIs.The results showed that compound16b was the most active inhibitor,exhibiting 50% effective concentration(EC50)values from 0.021μmol/L to 0.298μmol/L against wild-type(WT)and a panel of NNRTIs-resistant HIV-1 strains.Moreover,16b was demonstrated with a significantly low 50% cytotoxicity concentration(CC_(50))value(>200μmol/L)and high selectivity index(SI)values.In addition,16b yielded moderate reverse transcriptase(RT)enzyme inhibition with a 50% inhibition concentration(IC_(50))value of 0.183μmol/L,which demonstrated that it acted as HIV-1 NNRTIs.The binding mode of 16b with RT was also illustrated via molecular docking.Overall,this work provided a novel lead compound for developing potent HIV-1 NNRTIs.

Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase inhibitors.To fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design strategy.Most of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar levels.Among them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/L.Especially,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and etravirine.Besides,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and etravirine.The binding target of 23h was further confirmed to be HIV-1 reverse transcriptase.Molecular modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization campaign.Furthermore,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for 23h.Most importantly,23h was characterized by good pharmacokinetic properties and excellent safety in vivo.Collectively,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

Metal coordination-driven assembly of stimulator of interferon genes-activating nanoparticles for tumor chemo-immunotherapy

Activating the stimulator of interferon genes(STING)signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment(TME).Herein,we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist(i.e.,SR717)and a chemotherapeutic drug(i.e.,curcumin).After intravenous administration,the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune responses.Meanwhile,the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1,leading to the reversal of the immunosuppressive TME.The antitumor immunity induced by nanoparticles significantly inhibits the growth of primary,recurrent,and metastatic tumors.The assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy.

Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency

The syndrome of dampness stagnancy due to spleen deficiency(DSSD)is relatively common globally.Although the pathogenesis of DSSD remains unclear,evidence has suggested that the gut microbiota might play a significant role.Radix Astragali,used as both medicine and food,exerts the effects of tonifying spleen and qi.Astragalus polysaccharide(APS)comprises a macromolecule substance extracted from the dried root of Radix Astragali,which has many pharmacological functions.However,whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown.Here,we used DSSD rats induced by high-fat and low-protein(HFLP)diet plus exhaustive swimming,and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes,decreased the levels of interleukin-1β(IL-1β),IL-6,and endotoxin,and suppressed the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)pathway.Moreover,a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size(LEfSe).APS increased the diversity of the gut microbiota and changed its composition,such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella,and increasing that of Parasutterella,Parabacteroides,Clostridium XIVb,Oscillibacter,Butyricicoccus,and Dorea.APS also elevated the contents of short-chain fatty acids(SCFAs).Furthermore,the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes.In general,our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota,especially for some bacteria involving immune and inflammatory response and SCFA production,as well as the TLR4/NF-κB pathway.This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.

Loss of the vitamin D receptor triggers senescence in chronic myeloid leukemia via DDIT4-mediated DNA damage

Chronic myeloid leukemia(CML)is a hematopoietic malignancy driven by the fusion gene BCR::ABL1.Drug resistance to tyrosine kinase inhibitors(TKIs),due to BCR::ABL1 mutations and residual leukemia stem cells(LSCs),remains a major challenge in CML treatment.Here,we revealed the requirement of the vitamin D receptor(VDR)in the progression of CML.VDR was upregulated by BCR::ABL1 and highly expressed in CML cells.Interestingly,VDR knockdown inhibited the proliferation of CML cells driven by both BCR::ABL1 and TKI-resistant BCR::ABL1 mutations.Mechanistically,VDR transcriptionally regulated DDIT4 expression;reduced DDIT4 levels upon VDR knockdown triggered DNA damage and senescence via p53 signaling activation in CML cells.Furthermore,VDR deficiency not only suppressed tumor burden and progression in primary CML mice but also reduced the self-renewal capacity of CML-LSCs.Together,our study demonstrated that targeting VDR is a promising strategy to overcome TKI resistance and eradicate LSCs in CML.

Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation

Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

Precise design strategies of nanomedicine for improving cancer therapeutic efficacy using subcellular targeting

Therapeutic efficacy against cancer relies heavily on the ability of the therapeutic agents to reach their final targets.The optimal targets of most cancer therapeutic agents are usually biological macromolecules at the subcellular level,which play a key role in carcinogenesis.Therefore,to improve the therapeutic efficiency of drugs,researchers need to focus on delivering not only the therapeutic agents to the target tissues and cells but also the drugs to the relevant subcellular structures.In this review,we discuss the most recent construction strategies and release patterns of various cancer cell subcellular-targeting nanoformulations,aiming at providing guidance in the overall design of precise nanomedicine.Additionally,future challenges and potential perspectives are illustrated in the hope of enhancing anticancer efficacy and accelerating the translational progress of precise nanomedicine.

Studies on plasma-activated perilla seed oil:Diagnosis,optimisation,and validation of reactive species

Recently,the applications of cold atmospheric plasma(CAP)in liquid treatment have attracted increasing attention owing to its excellent medical efficacy.It has been proved that CAP can effectively enhance the biological activity of vegetable oils due to the generation of reactive species.Optimising the reactor parameter is an important approach to regulate reactive species in plasma-activated oil to obtain better biological effects.In this study,a self-made jet array driven by a pulsed power supply was used to generate large-area plasma to irradiate perilla seed oil(PSO),with the formation of plasmaactivated perilla seed oil(PAPSO).By means of laser-induced fluorescence and chemical titration,the relative density of hydroxyl radical radical in plasma jet,as well as the activity of PAPSO were measured under different discharge parameters,and realised the control of the activity of PAPSO.In vitro experiments showed that PAPSO significantly enhanced its ability to inhibit cancer cells proliferation and induce apoptosis after plasma treatment,which provides a reference for cancer treatment.This study is helpful to further understand the influence of plasma dose effect on the activity of media and provide guidance for related plasma medical applications.