Reconstituting membrane proteins in liposomes and determining their structure is a common method for determining membrane protein structures using single-particle cryo-electron microscopy(cryo-EM).However,the strong s...Reconstituting membrane proteins in liposomes and determining their structure is a common method for determining membrane protein structures using single-particle cryo-electron microscopy(cryo-EM).However,the strong signal of liposomes under cryo-EM imaging conditions often interferes with the structural determination of the embedded membrane proteins.Here,we propose a liposome signal subtraction method based on single-particle two-dimensional(2D)classification average images,aimed at enhancing the reconstruction resolution of membrane proteins.We analyzed the signal distribution characteristics of liposomes and proteins within the 2D classification average images of protein–liposome complexes in the frequency domain.Based on this analysis,we designed a method to subtract the liposome signals from the original particle images.After the subtraction,the accuracy of single-particle three-dimensional(3D)alignment was improved,enhancing the resolution of the final 3D reconstruction.We demonstrated this method using a PIEZO1-proteoliposome dataset by improving the resolution of the PIEZO1 protein.展开更多
A betamethasone dipropionate (BD) liposomal cream was developed to treat rheumatological, inflammatory, allergic diseases and psoriasis. BD is a corticosteroid, anti-inflammatory, and immunosuppressant. However, adver...A betamethasone dipropionate (BD) liposomal cream was developed to treat rheumatological, inflammatory, allergic diseases and psoriasis. BD is a corticosteroid, anti-inflammatory, and immunosuppressant. However, adverse effects are associated with prolonged topical use. For this reason, liposomes were loaded with BD because they offer excellent biocompatibility, bio adhesiveness, and penetrability that improve the effects caused by the conventional drug. Liposomal dispersions were prepared by emulsification using phospholipid 90 (lipid) and Tween 80 (surfactant). The particle size, polydispersity index (PDI), and zeta potential were measured using a particle analyzer. The betamethasone (BM) percentage of encapsulated active (EA) ingredient was also determined through High Performance Liquid Chromatography (HPLC). The Franz cell and tape stripping characterized these in vitro and ex vivo. Then the final formulation reached a particle size of 70.80 ± 3.31 nm, a PDI of 0.242 ± 0.038, a zeta potential of −11.68 ± 0.77 mv and encapsulate active of 83.1% ± 2.4, complying with the parameters of a nanotechnological formulation. In vitro and ex vivo studies confirmed significantly efficacy of the cream over the commercial product, through the greater penetration into the pig ear skin, resulting in an improved drug. Finally, the liposomal cream demonstrated significant potential for enhanced percutaneous absorption, attributed to its nanometric size. This innovative nanotechnology approach aims to reduce the frequency of topical applications, thereby minimizing the side effects associated with psoriasis treatment.展开更多
We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 ...We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 light chain 3 Beta,and autophagy-related gene 5 to inhibit autophagy,binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy,and interacts with glutathione peroxidase 4 to promote iron apoptosis.There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation.From a pharmaceutical point of view,there are certain requirements for Tau protein delivery systems,such as loading efficiency,stability,and targeting.Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency.Since Tau is a hydrophilic molecule with high water solubility,liposomes,micelles,and amphiphilic polymer nanoparticles may represent a superior choice.The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs,respectively,whereas Tau is expected to be loaded into the water region.In addition,a representative method of actively targeting hematopoietic stem cells is introduced.A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes(lecithin plus cholesterol).展开更多
Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor reg...Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.展开更多
[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl ...[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was investigated using a single factor method,and a quality evaluation system was established based on the appearance,particle size,PDI,and re-dispersibility of the lyophilized samples.[Results]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was determined by single factor experiments.The pre-freezing period was 16 h at-80℃,the total drying time was 36 h,and the addition of 10%mannitol-sucrose was used as the lyoprotectant.[Conclusions]The product prepared by the lyophilization method exhibits a fluffy and full appearance,with minimal shrinkage and collapse.The volume remains consistent before and after lyophilization,and the re-dispersibility is satisfactory.The re-dissolution process is rapid,and the particle size and polydispersity index(PDI)remain largely unchanged before and after lyophilization.展开更多
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,usual...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.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising i...Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.展开更多
目的探讨经尿道前列腺等离子双极电切术(transurethral plasmakinetic resection of prostate,TUPKP)治疗高危良性前列腺增生(BPH)患者的临床疗效。方法采用前瞻性多中心研究设计。在全国20家医院泌尿外科按照纳入排除标准,入组行TUPKP...目的探讨经尿道前列腺等离子双极电切术(transurethral plasmakinetic resection of prostate,TUPKP)治疗高危良性前列腺增生(BPH)患者的临床疗效。方法采用前瞻性多中心研究设计。在全国20家医院泌尿外科按照纳入排除标准,入组行TUPKP治疗的高危BPH患者,分析患者基线、围手术期及术后3个月随访的相关数据,评价疗效和安全性。结果2016年9月至2018年12月共入组229名高危BPH患者。与基线相比,术后3个月随访的国际前列腺症状评分改变量为-17.28[95%CI(-18.02,-16.54)]分、最大尿流率改变量为5.61[95%CI(0.68,10.54)]mL·s^(-1)、残余尿量改变量为-84.50[95%CI(-96.49,-72.51)]mL、生活质量评分改变量为-3.24[95%CI(-3.42,-3.06)]分,差异均具有统计学意义(P<0.05)。术中及术后并发症的发生率低,未发生与手术相关的不良事件。结论TUPKP可以用于治疗高危BPH患者,建议由技术熟练的术者实施手术。展开更多
基金Project supported by the National Natural Science Foundation of China (Grant Nos.32241023 and 92254306)the Fund from the Tsinghua–Peking Joint Center for Life SciencesBeijing Frontier Research Center for Biological Structure。
文摘Reconstituting membrane proteins in liposomes and determining their structure is a common method for determining membrane protein structures using single-particle cryo-electron microscopy(cryo-EM).However,the strong signal of liposomes under cryo-EM imaging conditions often interferes with the structural determination of the embedded membrane proteins.Here,we propose a liposome signal subtraction method based on single-particle two-dimensional(2D)classification average images,aimed at enhancing the reconstruction resolution of membrane proteins.We analyzed the signal distribution characteristics of liposomes and proteins within the 2D classification average images of protein–liposome complexes in the frequency domain.Based on this analysis,we designed a method to subtract the liposome signals from the original particle images.After the subtraction,the accuracy of single-particle three-dimensional(3D)alignment was improved,enhancing the resolution of the final 3D reconstruction.We demonstrated this method using a PIEZO1-proteoliposome dataset by improving the resolution of the PIEZO1 protein.
文摘A betamethasone dipropionate (BD) liposomal cream was developed to treat rheumatological, inflammatory, allergic diseases and psoriasis. BD is a corticosteroid, anti-inflammatory, and immunosuppressant. However, adverse effects are associated with prolonged topical use. For this reason, liposomes were loaded with BD because they offer excellent biocompatibility, bio adhesiveness, and penetrability that improve the effects caused by the conventional drug. Liposomal dispersions were prepared by emulsification using phospholipid 90 (lipid) and Tween 80 (surfactant). The particle size, polydispersity index (PDI), and zeta potential were measured using a particle analyzer. The betamethasone (BM) percentage of encapsulated active (EA) ingredient was also determined through High Performance Liquid Chromatography (HPLC). The Franz cell and tape stripping characterized these in vitro and ex vivo. Then the final formulation reached a particle size of 70.80 ± 3.31 nm, a PDI of 0.242 ± 0.038, a zeta potential of −11.68 ± 0.77 mv and encapsulate active of 83.1% ± 2.4, complying with the parameters of a nanotechnological formulation. In vitro and ex vivo studies confirmed significantly efficacy of the cream over the commercial product, through the greater penetration into the pig ear skin, resulting in an improved drug. Finally, the liposomal cream demonstrated significant potential for enhanced percutaneous absorption, attributed to its nanometric size. This innovative nanotechnology approach aims to reduce the frequency of topical applications, thereby minimizing the side effects associated with psoriasis treatment.
基金Supported by the National Natural Science Foundation of China,No.82373800Guangdong Basic and Applied Basic Research Foundation,No.2024A1515011236General Program of Administration of Traditional Chinese Medicine of Guangdong Province,No.20241071.
文摘We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 light chain 3 Beta,and autophagy-related gene 5 to inhibit autophagy,binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy,and interacts with glutathione peroxidase 4 to promote iron apoptosis.There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation.From a pharmaceutical point of view,there are certain requirements for Tau protein delivery systems,such as loading efficiency,stability,and targeting.Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency.Since Tau is a hydrophilic molecule with high water solubility,liposomes,micelles,and amphiphilic polymer nanoparticles may represent a superior choice.The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs,respectively,whereas Tau is expected to be loaded into the water region.In addition,a representative method of actively targeting hematopoietic stem cells is introduced.A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes(lecithin plus cholesterol).
基金funding from the Liaoning Province Doctoral Start-up(grant number 2023-BS-086).
文摘Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.
基金Youth Science Foundation Project of Sichuan Provincial Department of Science and Technology(2022NSFSC1437)Special Project of Scientific and Technological Research of Sichuan Provincial Administration of Traditional Chinese Medicine(2021MS121)Fundamental Research Funds for the Central Universities of Southwest Minzu University(ZYN2022040).
文摘[Objectives]To enhance the skin permeability of hydroxypropyl tetrahydropyrantriol and provide a reference for the subsequent prevention or treatment of skin aging.[Methods]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was investigated using a single factor method,and a quality evaluation system was established based on the appearance,particle size,PDI,and re-dispersibility of the lyophilized samples.[Results]The lyophilization process of hydroxypropyl tetrahydropyrantriol liposomes was determined by single factor experiments.The pre-freezing period was 16 h at-80℃,the total drying time was 36 h,and the addition of 10%mannitol-sucrose was used as the lyoprotectant.[Conclusions]The product prepared by the lyophilization method exhibits a fluffy and full appearance,with minimal shrinkage and collapse.The volume remains consistent before and after lyophilization,and the re-dispersibility is satisfactory.The re-dissolution process is rapid,and the particle size and polydispersity index(PDI)remain largely unchanged before and after lyophilization.
基金supported by the National Natural Science Foundation of China[grant numbers 21873057,22373059]the Natural Science Foundation of Shandong Province[grant numbers ZR2023MB082]。
文摘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.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
基金funded by the Optimization Study of Treatment Regimen and Clinical Practice in Ovarian Cancer(grant number:2016YFC1303702).
文摘Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.
文摘目的探讨经尿道前列腺等离子双极电切术(transurethral plasmakinetic resection of prostate,TUPKP)治疗高危良性前列腺增生(BPH)患者的临床疗效。方法采用前瞻性多中心研究设计。在全国20家医院泌尿外科按照纳入排除标准,入组行TUPKP治疗的高危BPH患者,分析患者基线、围手术期及术后3个月随访的相关数据,评价疗效和安全性。结果2016年9月至2018年12月共入组229名高危BPH患者。与基线相比,术后3个月随访的国际前列腺症状评分改变量为-17.28[95%CI(-18.02,-16.54)]分、最大尿流率改变量为5.61[95%CI(0.68,10.54)]mL·s^(-1)、残余尿量改变量为-84.50[95%CI(-96.49,-72.51)]mL、生活质量评分改变量为-3.24[95%CI(-3.42,-3.06)]分,差异均具有统计学意义(P<0.05)。术中及术后并发症的发生率低,未发生与手术相关的不良事件。结论TUPKP可以用于治疗高危BPH患者,建议由技术熟练的术者实施手术。
