The protein corona formation has been reported to influence the liposomes’behavioral performance in vivo.Accordingly,the effect of physiologically relevant inorganic ion pairs(sodium chloride,sodium sulfate,magnesium...The protein corona formation has been reported to influence the liposomes’behavioral performance in vivo.Accordingly,the effect of physiologically relevant inorganic ion pairs(sodium chloride,sodium sulfate,magnesium chloride,and magnesium sulfate)was investigated.Bovine serum albumin(BSA)was selected as the model protein.Parameters including particle size and zeta potential were assessed,while various spectroscopic techniques were utilized to elucidate the changes in BSA during its interaction with liposomes.The particle size and light intensity distribution changes indicated that the introduction of inorganic pairs,especially the metal cations,could significantly influence both the adsorption of BSA and the aggregation of particles.Furthermore,spectral characterization elucidated that BSA exhibited more extended peptide chains with enhanced exposure to hydrophobic acid amino residues upon adding ion pairs.Electrostatic adsorption and chelation insertion were proposed as metal ion binding modes and the corresponding BSA corona formation.In the electrostatic adsorption mode,sodium ions can enhance the electrostatic interactions,facilitating the“connection”between BSA and liposomes.Magnesium ions can induce stronger hydrophobic interactions through chelation,effectively“drag”BSA segments into the lipid bilayer.This work highlighted important physiological factors for protein-liposome interaction and provided rational model constructions to lay the foundation for further relevant studies.展开更多
Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self...Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.展开更多
Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which...Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.展开更多
Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to ...Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.展开更多
Objective:This study aimed to prepare doxorubicin hydrochloride liposomes and explore their application value in patients with liver cancer.Methods:Doxorubicin hydrochloride liposomes were prepared using the ammonium ...Objective:This study aimed to prepare doxorubicin hydrochloride liposomes and explore their application value in patients with liver cancer.Methods:Doxorubicin hydrochloride liposomes were prepared using the ammonium sulfate gradient method.Doxorubicin,as a broad-spectrum antitumor drug,has significant toxic and side effects after toxicological investigation.After preparing DOX-Lip,single-factor analysis was used to analyze the effects of solution pH,number of ultrafiltration,oil-water ratio,incubation temperature,and time on the encapsulation efficiency of doxorubicin hydrochloride liposomes.The process was optimized through orthogonal experiments and then applied clinically.110 patients with liver cancer were selected as the research subjects to verify the drug’s effectiveness.Results:The results of this study showed that under optimal process conditions,the prepared doxorubicin hydrochloride liposomes were evenly distributed,similar to spherical shapes,with an average particle size of 85–87 mm and a Zeta potential of 15–16 mV,indicating good encapsulation efficiency.The application of these liposomes to clinical treatment of liver cancer demonstrated good therapeutic effects and could effectively promote favorable patient prognosis.Conclusion:The doxorubicin hydrochloride liposomes prepared through process optimization exhibit strong stability and pronounced sustained-release characteristics,providing a solid foundation for the treatment of liver cancer.展开更多
As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effective...As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.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
Six factors and 10 levels of each factor were selected by using the (uniform design method( with the aid of the computer for preparing APS liposomes. The optimal procedure for preparing APS liposomes was established a...Six factors and 10 levels of each factor were selected by using the (uniform design method( with the aid of the computer for preparing APS liposomes. The optimal procedure for preparing APS liposomes was established and it can suit the large scale production in a pharmaceutical factory. The shelf-life of APS liposomes at 20℃ is 1.46 years. Diameters of the vesicles ( > 90% ) in APS liposomes are less than 1 μm, and the system is stable. At 40℃ the diameters of vesicles were not changed in three months. Pharmacological experiments revealed that APS liposomes exerted a strong immunoenhancement in mice. Studies in this paper established a foundation for the production and the clinical application of APS liposomes.展开更多
One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transderm...One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel （DTX）, a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes （SEL） were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application condi- tions. The DTX SELs with optimum composition （phospholipid-surfactant, 85：15, w/w） provided a significantly higher steadystate amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.展开更多
Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffol...Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.展开更多
Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To ad...Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.展开更多
To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and...To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.展开更多
Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tiss...Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.展开更多
Aim Peptides as ligands have shown the active targeting properties to the receptors like integrins, a family of receptors over-expressed in cancers. The present study was to develop and characterize two peptides modif...Aim Peptides as ligands have shown the active targeting properties to the receptors like integrins, a family of receptors over-expressed in cancers. The present study was to develop and characterize two peptides modified drug-containing liposomes. Methods Argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine-aspartic acid-serine （GRGDS） pentapeptide were used for modifications on the doxorubicin-loaded sterically stabilized liposomes （SSL-doxorubicin） for the liposome preparation, RGD-SSL-doxorubicin and GRGDS-SSL-doxorubicin, respectively. Characterizations were performed by measurements of the encapsulation efficiency, particle size and zeta potential, release rates in a simulated in vivo environment, and cytotoxicity to ovarian cancer cells. Cell uptake was investigated by flow cytometry and confocal microscopy methods. Results All encapsulation efficiencies of the liposomes were above 95%, and the modifications using RGD or GRGDS did not affect the final encapsulation efficiency. Average particle sizes of the liposomes Were in the range between 105.7 ± 3.5 nm and 130.5 ± 3.0 nm, and zeta potential values were between -3.3 ± 0.3 and -6.1 ± 0.3 mV. Approximately 2/5 of doxorubicin was released from liposomes before 12 h in the simulated in vivo environment containing fetal bovine serum. Inhibitory rates to cancer cells of the modified liposomes were slightly lower as compared to free doxorubicin. Similar phenomena were observed in the uptake measured by flow cytometry and confocal assay. After uptake applying various formulations on the cancer cells, doxorubicin was mainly distributed in the nuclei of SKOV-3 cells. Conclusion Two new doxorubicin-contained liposomes were successfully prepared and modified with argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine- aspartic acid-serine （GRGDS） pentapeptide. In vitro characterization indicated that modifications did not alter significantly the properties of the sterically stabilized liposomes.展开更多
This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were exa...This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were examined. Visible spectrophotometry and the HPLC method were established for determination of the DNR in the DNRSL. The release of DNR from DNRSL in HBS (pH 7.5) and rat serum at 37 oC were examined. The results showed that the DNRSL had high entrapment efficiency (>85%), small size and slow release.展开更多
An anti-trichomonas vaginalis monoclonal antiboody was derivatized with palmitic acid using an activated ester of N-hydroxysuccinimide About 50% of the re-sulting antibody could be incorporated into liposomes.The lipo...An anti-trichomonas vaginalis monoclonal antiboody was derivatized with palmitic acid using an activated ester of N-hydroxysuccinimide About 50% of the re-sulting antibody could be incorporated into liposomes.The liposomes showed specific binding to T. vaginalis by IFA and cytotoxicity tests. These results clearly demonstrated the effectiveness of targeting of liposomes modified by monoclonal antibody in vitro.展开更多
The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths...The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths were documented globally.COVID-19 has been rapidly evolving,affecting virus transmissibility and properties and contributing to increased disease severity.The Omicron is themost circulating variant of concern.Although success in its treatment has indicated progress in tackling the virus,limitations in delivering the current antiviral agents in battling emerging variants remain remarkable.With the latest advancements in nanotechnology for controlling infectious diseases,liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies,incorporating monoclonal antibodies for the active and passive targeting of infected patients.This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARSCoV-2 and its variants.展开更多
Hepatocellular carcinoma （HCC） is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous...Hepatocellular carcinoma （HCC） is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel （DTX） and small interfering RNA （siRNA）. The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.展开更多
In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared...In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared with a narrow size distribution below 200 nm. It was shown that the encapsulated siRNA in the liposomes could be effectively protected from serum degradation. Also, enhanced cell binding and intracellular uptake of siRNA in the doxorubicin-resistant human ova- rian cancer cell lines SKOV3/A were found in RGD-Lipo-siRNA preparation as compared to that of unmodified cationic lipsomes （Lipo-siRNA）. Using the post-insertion method for RGD modification, lysosome release of siRNA in pRGD-Lipo-siRNA was improved. From flow cytometry, significant increase of doxorubicin accumulation was observed in the SKOV3/A cells treated with pRGD-Lipo-siRNA targeting human MDR1 gene. In vitro cytotoxicity assay showed that the significant cell growth inhibition was achieved in the SKOV3/A cells after treating with the combined use of siRNA and doxorubicin. In conclusions, postinserted RGD modified lipoplex, pRGD-Lipo-siRNA, was successfully used for siRNA transfection and achieved drug resistance reversal in human ovarian cancer SKOV3/A （doxorubicin-resistant） cells. It suggested that this liposomes might be a potential vehicle for siRNA delivery in vivo.展开更多
Liposomes were prepared by adding hydrophilic agents PEG PE, rigidity agent SM in the bilayer membrane for mimetic red cell membrane. In PBS or serum, release of calcein content from liposomes dramatically decreased,...Liposomes were prepared by adding hydrophilic agents PEG PE, rigidity agent SM in the bilayer membrane for mimetic red cell membrane. In PBS or serum, release of calcein content from liposomes dramatically decreased, which demonstrated increasing membrane stability by adding PEG PE or SM. The ratio b/R of the remains of liposomes in blood to that in RES was used as a parameter of biodistribution in vivo. At 2 h after iv injection, b/R of modified liposomes was enhanced 6.5～13.1 fold. Their clearance half life from blood circulation was delayed 1.6～5.8 fold. The modification of liposome membrane by PEG PE or SM is the favorable condition for drug liposomes to target the non RES.展开更多
基金supported by the National Natural Science Foundation of China(No.82373800)Guangdong Basic and Applied Basic Research Foundation(No.2024A1515011236)Continuation"Project of Excellent Doctors,Guangzhou Basic and Applied Basic Research Foundation(No.2025A04J5082).
文摘The protein corona formation has been reported to influence the liposomes’behavioral performance in vivo.Accordingly,the effect of physiologically relevant inorganic ion pairs(sodium chloride,sodium sulfate,magnesium chloride,and magnesium sulfate)was investigated.Bovine serum albumin(BSA)was selected as the model protein.Parameters including particle size and zeta potential were assessed,while various spectroscopic techniques were utilized to elucidate the changes in BSA during its interaction with liposomes.The particle size and light intensity distribution changes indicated that the introduction of inorganic pairs,especially the metal cations,could significantly influence both the adsorption of BSA and the aggregation of particles.Furthermore,spectral characterization elucidated that BSA exhibited more extended peptide chains with enhanced exposure to hydrophobic acid amino residues upon adding ion pairs.Electrostatic adsorption and chelation insertion were proposed as metal ion binding modes and the corresponding BSA corona formation.In the electrostatic adsorption mode,sodium ions can enhance the electrostatic interactions,facilitating the“connection”between BSA and liposomes.Magnesium ions can induce stronger hydrophobic interactions through chelation,effectively“drag”BSA segments into the lipid bilayer.This work highlighted important physiological factors for protein-liposome interaction and provided rational model constructions to lay the foundation for further relevant studies.
基金supported by the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University(No.2024LZXNYDJ017)the Project Program of the Science and Technology Department of Sichuan Province(No.2025zNSFSC0679)the Project Program of Chongqing Science and Technology Bureau(No.cstc2020jcyjmsxmX1037).
文摘Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.
基金supported by the National Natural Science Foundation of China (Nos.81872823,82073782,and 82241002)the Key R&D Plan of Ganjiang New District of Jiangxi (No.2023010)。
文摘Cisplatin(CDDP)-based chemotherapy is an effective strategy for the treatment of advanced nasopharyngeal carcinoma(NPC).However,serious toxic side effects of CDDP limit patient tolerance and treatment compliance,which urgently needs to be addressed in clinical application.Liposomes have been considered ideal vehicles for reducing CDDP toxicity due to their high biocompatibility,low toxicity and passive targeting ability.Nevertheless,CDDP's poor water/lipid solubility usually results in a low liposome druglipid ratio,limiting tumor delivery ability.Herein,a CDDP-polyphenol complex liposome was designed to increase the drug loading capacity of CDDP to realize the reduction of toxicity and effective antitumor effect simultaneously.The complex was prepared via complexation reaction of different stoichiometric ratios of CDDP and polyphenolic substances(gallic acid,epigallocatechin gallate and tannic acid),followed by encapsulation of complex in liposomes to improve tumor targeting.Notably,the molecular interaction forces between CDDP and polyphenolic substances were intensively investigated through a binding force disruption assay.In vitro studies demonstrated that the optimal formulation of CDDP-epigallocatechin gallate complex liposome(CDDP-EGCG Lips) showed the highest CDDP encapsulation efficiency,favorable stability,pH-sensitive release,enhanced cellular uptake and apoptosis effect.In vivo studies revealed that CDDP-EGCG Lips retarded the elimination of CDDP to prolong their circulation time,inhibited the growth of tumors,and significantly reduced the toxic side effects compared to CDDP monotherapy.This delivery strategy holds great promise for improving the clinical use of platinum-based drugs.
文摘Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.
文摘Objective:This study aimed to prepare doxorubicin hydrochloride liposomes and explore their application value in patients with liver cancer.Methods:Doxorubicin hydrochloride liposomes were prepared using the ammonium sulfate gradient method.Doxorubicin,as a broad-spectrum antitumor drug,has significant toxic and side effects after toxicological investigation.After preparing DOX-Lip,single-factor analysis was used to analyze the effects of solution pH,number of ultrafiltration,oil-water ratio,incubation temperature,and time on the encapsulation efficiency of doxorubicin hydrochloride liposomes.The process was optimized through orthogonal experiments and then applied clinically.110 patients with liver cancer were selected as the research subjects to verify the drug’s effectiveness.Results:The results of this study showed that under optimal process conditions,the prepared doxorubicin hydrochloride liposomes were evenly distributed,similar to spherical shapes,with an average particle size of 85–87 mm and a Zeta potential of 15–16 mV,indicating good encapsulation efficiency.The application of these liposomes to clinical treatment of liver cancer demonstrated good therapeutic effects and could effectively promote favorable patient prognosis.Conclusion:The doxorubicin hydrochloride liposomes prepared through process optimization exhibit strong stability and pronounced sustained-release characteristics,providing a solid foundation for the treatment of liver cancer.
基金supported by the National Natural Science Foundation of China(Nos.82373817 and 82003659)Shanghai Natural Science Foundation(No.23ZR1477500)Pudong Health Bureau of Shanghai(No.YC-2023-0401)。
文摘As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.
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.
文摘Six factors and 10 levels of each factor were selected by using the (uniform design method( with the aid of the computer for preparing APS liposomes. The optimal procedure for preparing APS liposomes was established and it can suit the large scale production in a pharmaceutical factory. The shelf-life of APS liposomes at 20℃ is 1.46 years. Diameters of the vesicles ( > 90% ) in APS liposomes are less than 1 μm, and the system is stable. At 40℃ the diameters of vesicles were not changed in three months. Pharmacological experiments revealed that APS liposomes exerted a strong immunoenhancement in mice. Studies in this paper established a foundation for the production and the clinical application of APS liposomes.
基金The Key Direction Program of Chinese Academy of Sciences(Grant No.kjcx2-sw-h12-01)
文摘One major problem encountered in transdermal drug delivery is the low permeability of drugs through the skin barrier. In the present study, we developed a surfactant-ethanolic liposomal system to improve the transdermal delivery of docetaxel （DTX）, a model drug for high molecular weight and poorly water-soluble drugs. Surfactant-ethanolic liposomes （SEL） were composed of phospholipids, ethanol, sodium cholate, DTX and PBS which were prepared by thin film dispersion method. The developed formulations were characterized by determining the vesicle shape and surface morphology, size and size distribution, entrapment efficiency and drug loading capacity. The effects of the developed formulations on the permeation of DTX across rat skin in vitro were investigated using the modified Franz diffusion cell under both occlusive and non-occlusive application condi- tions. The DTX SELs with optimum composition （phospholipid-surfactant, 85：15, w/w） provided a significantly higher steadystate amount of flux and cumulative permeation, compared to the tranditional liposomes, surfactant liposomes and ethanolic liposomes. The optimal SELs exhibited stable vesicle size, morphology and drug loading capacity. Our results indicated that SELs were promising carriers to enhance the transdermal delivery of DTX.
基金supported by grants from the China Postdoctoral Science Foundation(Nos.2022TQ0397,2022MD723744,2022M710564,2022M720603)Natural Science Foundation of China(Nos.82272553,82102571,81974346,8210257,82472404)+8 种基金Chongqing Municipal Medical Youth Talent Support Program,Chongqing,China(No.YXQN202408)Natural Science Foundation of Chongqing,China(Nos.CSTB2022NSCQ-MSX0089,CSTB2022NSCQ-MSX0104,CSTB2024NSCQMSX0532)Joint Medical Research Project of Health Commission&Science and Technology Bureau of Chongqing,China(No.2024QNXM032)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(No.2023ZYD0071)National Natural Science Foundation of Sichuan(No.24NSFSC1274)Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee,Chongqing,China(Nos.CYS22389,CYB240224)National Natural Science Foundation of Sichuan(No.2024NSFSC0678)Research Project of the Affiliated Hospital of North Sichuan Medical College(Nos.2023ZD002,2023-2ZD001,2024JB001)Disciplines Construction Program of The Third Affiliated Hospital of Chongqing Medical University(Nos.KY23035,KY23041).
文摘Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.
基金supported by the Macao Science and Technology Development Fund (FDCT 0148/2022/A3 and 0019/2024/RIA1)the National Natural Science Foundation of China (No. 81572979)
文摘Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.
基金supported by the National Natural Science Foundation of China (No. 82074277 and 81773911)the Development Project of Shanghai Peak Disciplines-Integrated Medicine (No. 20180101)
文摘To utilize themultiple functions and give full play of ginsenosides,a variety of ginsenosides with different structures were prepared into liposomes and evaluated for their effect on the stability,pharmacokinetics and tumor targeting capability of liposomes.The results showed that the position and number of glycosyl groups of ginsenosides have significant effect on the in vitro and in vivo properties of their liposomes.The pharmacokinetics of ginsenosides liposomes indicated that the C-3 sugar group of ginsenosides is beneficial to their liposomes for longer circulation in vivo.The C-3 and C-6 glycosyls can enhance the uptake of their liposomes by 4T1 cells,and the glycosyls at C-3 position can enhance the tumor active targeting ability significantly,based on the specific binding capacity to Glut 1 expressed on the surface of 4T1 cells.According to the results in the study,ginsenoside Rg3 and ginsenoside Rh2 are potential for exploiting novel liposomes because of their cholesterol substitution,long blood circulation and tumor targeting capabilities.The results provide a theoretical basis for further development of ginsenoside based liposome delivery systems.
文摘Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.
基金National Natural Science Foundation of China(Grant No. 30572261)the 985 Projects (Phase II) of theState Key Laboratory of Natural and Biomimetic Drugs(Peking University, China).
文摘Aim Peptides as ligands have shown the active targeting properties to the receptors like integrins, a family of receptors over-expressed in cancers. The present study was to develop and characterize two peptides modified drug-containing liposomes. Methods Argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine-aspartic acid-serine （GRGDS） pentapeptide were used for modifications on the doxorubicin-loaded sterically stabilized liposomes （SSL-doxorubicin） for the liposome preparation, RGD-SSL-doxorubicin and GRGDS-SSL-doxorubicin, respectively. Characterizations were performed by measurements of the encapsulation efficiency, particle size and zeta potential, release rates in a simulated in vivo environment, and cytotoxicity to ovarian cancer cells. Cell uptake was investigated by flow cytometry and confocal microscopy methods. Results All encapsulation efficiencies of the liposomes were above 95%, and the modifications using RGD or GRGDS did not affect the final encapsulation efficiency. Average particle sizes of the liposomes Were in the range between 105.7 ± 3.5 nm and 130.5 ± 3.0 nm, and zeta potential values were between -3.3 ± 0.3 and -6.1 ± 0.3 mV. Approximately 2/5 of doxorubicin was released from liposomes before 12 h in the simulated in vivo environment containing fetal bovine serum. Inhibitory rates to cancer cells of the modified liposomes were slightly lower as compared to free doxorubicin. Similar phenomena were observed in the uptake measured by flow cytometry and confocal assay. After uptake applying various formulations on the cancer cells, doxorubicin was mainly distributed in the nuclei of SKOV-3 cells. Conclusion Two new doxorubicin-contained liposomes were successfully prepared and modified with argine-glycine-aspartic acid （RGD） tripeptide and glycine-argine-glycine- aspartic acid-serine （GRGDS） pentapeptide. In vitro characterization indicated that modifications did not alter significantly the properties of the sterically stabilized liposomes.
文摘This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were examined. Visible spectrophotometry and the HPLC method were established for determination of the DNR in the DNRSL. The release of DNR from DNRSL in HBS (pH 7.5) and rat serum at 37 oC were examined. The results showed that the DNRSL had high entrapment efficiency (>85%), small size and slow release.
文摘An anti-trichomonas vaginalis monoclonal antiboody was derivatized with palmitic acid using an activated ester of N-hydroxysuccinimide About 50% of the re-sulting antibody could be incorporated into liposomes.The liposomes showed specific binding to T. vaginalis by IFA and cytotoxicity tests. These results clearly demonstrated the effectiveness of targeting of liposomes modified by monoclonal antibody in vitro.
基金the financial support obtained from Universiti Kebangsaan Malaysia(DIP-2021-001)ASEANIndia Science&Technology Development Fund(AISTDF)(SERB/F/3955/2022-2023).
文摘The global COVID-19 pandemic arising from SARS-CoV-2 has impacted many lives,gaining interest worldwide ever since it was first identified in December 2019.Till 2023,752 million cumulative cases and 6.8 million deaths were documented globally.COVID-19 has been rapidly evolving,affecting virus transmissibility and properties and contributing to increased disease severity.The Omicron is themost circulating variant of concern.Although success in its treatment has indicated progress in tackling the virus,limitations in delivering the current antiviral agents in battling emerging variants remain remarkable.With the latest advancements in nanotechnology for controlling infectious diseases,liposomes have the potential to counteract SARS-CoV-2 because of their ability to employ different targeting strategies,incorporating monoclonal antibodies for the active and passive targeting of infected patients.This review will present a concise summary of the possible strategies for utilizing immunoliposomes to improve current treatment against the occurrence of SARSCoV-2 and its variants.
基金National Natural Science Foundation of China(Grant No.81273454)Beijing National Science Foundation(Grant No.7132113)+1 种基金Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)Innovation Team of Ministry of Education(Grant No.BMU20110263)
文摘Hepatocellular carcinoma （HCC） is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel （DTX） and small interfering RNA （siRNA）. The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.
基金National Natural Science Foundation of China(Grant No.30701056)Foundation of MOST(973 Program,Grant No.2007CB935801)+1 种基金Beijing Natural Science Foundation of China(Grant No.7083112)Doctoral Foundation of Ministry of Education of China(Grant No.20070001813).
文摘In this study, the novel RGD-modified stabilized cationic liposomes were developed as the delivery vehicle for siRNA targeting human MDR1 gene. The complex of cationic liposomes and siRNA, RGD-Lipo-siRNA, was prepared with a narrow size distribution below 200 nm. It was shown that the encapsulated siRNA in the liposomes could be effectively protected from serum degradation. Also, enhanced cell binding and intracellular uptake of siRNA in the doxorubicin-resistant human ova- rian cancer cell lines SKOV3/A were found in RGD-Lipo-siRNA preparation as compared to that of unmodified cationic lipsomes （Lipo-siRNA）. Using the post-insertion method for RGD modification, lysosome release of siRNA in pRGD-Lipo-siRNA was improved. From flow cytometry, significant increase of doxorubicin accumulation was observed in the SKOV3/A cells treated with pRGD-Lipo-siRNA targeting human MDR1 gene. In vitro cytotoxicity assay showed that the significant cell growth inhibition was achieved in the SKOV3/A cells after treating with the combined use of siRNA and doxorubicin. In conclusions, postinserted RGD modified lipoplex, pRGD-Lipo-siRNA, was successfully used for siRNA transfection and achieved drug resistance reversal in human ovarian cancer SKOV3/A （doxorubicin-resistant） cells. It suggested that this liposomes might be a potential vehicle for siRNA delivery in vivo.
文摘Liposomes were prepared by adding hydrophilic agents PEG PE, rigidity agent SM in the bilayer membrane for mimetic red cell membrane. In PBS or serum, release of calcein content from liposomes dramatically decreased, which demonstrated increasing membrane stability by adding PEG PE or SM. The ratio b/R of the remains of liposomes in blood to that in RES was used as a parameter of biodistribution in vivo. At 2 h after iv injection, b/R of modified liposomes was enhanced 6.5～13.1 fold. Their clearance half life from blood circulation was delayed 1.6～5.8 fold. The modification of liposome membrane by PEG PE or SM is the favorable condition for drug liposomes to target the non RES.
