JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Xiaolei Ma,Rui Cong,Xin Cui,Yiwei Tang,Jie Ren,Jinfan Hou,Boyu Liu,Jiehui Zhao,Pengwei Li,Lei Li,Heyang Zhang,Jiasheng Tu,Lei Jiang
Psoriasis is a prevalent chronic inflammatory skin disease characterized by immune cell activation and aberrant keratinocyte proliferation. Signal transducer and activator of transcription 3 (STAT3) plays a key role in the pathology of psoriasis, positioning it as a promising target for therapeutic strategies. However, current STAT3 inhibitors often lack specificity, leading to adverse effects. Here, we present the development of dendritic lipopeptides (DLPs) designed to facilitate the transdermal delivery of small interfering RNA (siRNA) to specifically inhibit STAT3 expression in psoriatic lesions. The dendritic architecture and peptide composition of DLP are crucial for interaction with keratin of stratum corneum and gene transfection efficiency, while the lipid chain selection aims to increase lipophilicity and enhance interactions with cellular membranes. We conducted extensive in vitro and in vivo investigations to assess the therapeutic efficacy of these DLPs for siRNA delivery in psoriasis treatment. The results demonstrated that our DLPs effectively penetrated the skin barrier, delivered siRNA to target cells, and significantly reduced STAT3 expression, regulated immune cell imbalance, leading to a marked improvement in psoriasis symptoms. In conclusion, our study presents a promising non-invasive approach to psoriasis treatment by focusing on the targeted suppression of STAT3 expression. The dendritic lipopeptides offer a safe and effective platform of siRNA delivery, potentially revolutionizing the management of psoriasis and other chronic inflammatory dermatological conditions.
研究领域:
皮肤病学
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分子生物学
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药物递送
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2015
·
IF 1.648
Ju Liang,Wenlan Wu,Danyu Lai,Junbo Li,Cailin Fang
A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 103 times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.
研究领域:
药剂学
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肿瘤学
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生物材料
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2015
·Vol. 16
·期 1
·1855-1872
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IF 2.862
Chuanshi Shao,Lin Liu,Hongze Gang,Shizhong Yang,Bozhong Mu
Surfactin originated from genusBacillusis composed of a heptapeptide moiety bonded to the carboxyl and hydroxyl groups of a β-hydroxy fatty acid and it can be chemically modified to prepare the derivatives with different structures, owing to the existence of two free carboxyl groups in its peptide loop. This article presents the chemical modification of surfactin esterified with three different alcohols, and nine novel surfactin derivatives have been separated from products by the high performance liquid chromatography (HPLC). The novel derivatives, identified with Fourier transform infrared spectroscopy (FT-IR) and electrospray ionization mass spectrometry (ESI-MS), are the mono-hexyl-surfactin C14 ester, mono-hexyl-surfactin C15 ester, mono-2-methoxy-ethyl-surfactin C14 ester,di-hexyl-surfactin C14 ester,di-hexyl-surfactin ester C15,di-2-methoxy-ethyl-surfactin ester C14,di-2-methoxy-ethyl-surfactin ester C15,di-6-hydoxyl-hexyl-surfactin C14 ester and,di-6-hydoxyl-hexyl-surfactin C15 ester. The reaction conditions for esterification were optimized and the dependence of yields on different alcohols and catalysts were discussed. This study shows that esterification is one of the most efficient ways of chemical modification for surfactin and it can be used to prepare more derivatives to meet the needs of study in biological and interfacial activities.Keywords:Keywords: surfactin;esterification;derivatives;lipopeptide;carboxyl group
研究领域:
微生物学
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生物化学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2017
·Vol. 5
·期 7
·1482-1497
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IF 4.543
Xiaobing Chen,Jun Yang,Hong Liang,Qian Jiang,Bowen Ke,Yu Nie
Integrating the advantages of artificial vectors with bioinspired strategies has opened interesting perspectives in the design of gene delivery systems. Herein, disulfide modified, self-assembled lipopeptides with arginine-rich periphery are demonstrated as gene vectors (RLS). It is surprising that these carriers achieved excellent gene transfection efficacy (up to 380-fold higher than PEI) in different cell lines (HeLa and B16 cells) at relatively low N/P (∼10) ratios, compared to the analog lipopeptides without disulfide bonds (RL, N/P 40). As shown from the morphologies observed by transmission electronic microscopy and surface charge detection by dynamic light scattering, the existence of disulfide bonds may influence the configuration/conformation of the RLS assembly with decreased zeta potential (+27.2 mV), compared to that of the analogs, RL (+46.5 mV). Correspondingly, RLS/DNA complexes showed relatively lower zeta potentials than those of RL/DNA complexes at different N/P ratios. Under the transfection conditions, RLS/DNA complexes (N/P 10) showed even less cellular uptake than that of RL/DNA complexes (N/P 40), and no difference was detected in buffering effect and endosomal escape between RLS and RL complexes. Examination by gel electrophoresis and fluorescence resonance energy transfer (FRET) images in cell culture conditions confirmed that RLS lipoplexes could effectively liberate DNA. Thus, the higher gene transfection efficiency of disulfide modified vectors might be mainly attributed to the cleavage of disulfide bonds; the rapid release of DNA and the superiority of the design was closely related to the reductive conditions in the cells.
研究领域:
生物化学
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分子生物学
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药物递送
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DOI
PubMed
高影响因子
ACTA PHYSICO-CHIMICA SINICA
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2017
·Vol. 33
·期 4
·829-835
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IF 0.767
WANG Si-Jia,LI Meng-Ya,XU Shou-Hong,LIU Hong-Lai
The leucine zipper lipopeptide is a dimer composed of two lipopeptides with α-helical structures that interact through hydrophobic forces. When heated to its phase transition temperature, the helixes unwind and form a disordered conformation. Based on the thermo-sensitivity of
these leucine zipper lipopeptides, we designed and synthesized a series of zipper-structured lipopeptides and then mixed them with lipids to form thermo-sensitive hybrid liposomes. Circular dichroism was used to investigate the secondary structure of the lipopeptides anchored in the liposomal
bilayer. Dynamic light scattering measurements were used to assess the diameters and zeta potentials of the liposomes. Fluorescence polarization was measured to study the fluidity of the liposomal bilayer. An ultraviolet spectrophotometer was used to stimulate Doxorubicin (DOX) release in
vitro at 37.0 and 45.0°C. We found that Lp-Lipo (hybrid of lipopeptide and liposome) displayed higher thermosensitivity than pure liposome. The cholesterol content and fluidity of the liposomal bilayer affected the thermocontrolled on-off switch of the lipopeptides.
Lp-Lipo shows great potential as a novel thermo-sensitive drug carrier.
研究领域:
生物化学
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药剂学
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分子生物学
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DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2019
·Vol. 103
·期 13
·5367-5377
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IF 3.67
Ding Lianshuai,Guo Wenbin,Chen Xinhua
The bacterium, Bacillus amyloliquefaciens Pc3, was previously isolated from Antarctic seawater and has been found to show antagonistic activity against the fungus, Rhizoctonia solani ACCC 36316, which causes a severe disease known as Sclerotinia sclerotiorum in rapeseed plants. Bacillus lipopeptides had been widely used as biocontrol agents for plant diseases. In this study, we isolated 11 lipopeptide compounds from B. amyloliquefaciens Pc3 culture broth via reversed-phase high-performance liquid chromatography (RP-HPLC) and used matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to identify these as iturin A (C 14 , C 15 , C 16 , C 17 ), fengycin B (C 14 , C 15 , C 16 , C 17 ), and surfactin (C 14 , C 15 , C 16 ). We further found that the addition of exogenous alkanoic acids, including myristic acid, pentadecanoic acid, palmitic acid, heptadecanoic acid, octadecanoic acid, and nonadecanoic acid, to the bacterial growth media could promote lipopeptide production and enhance the antifungal activities of crude lipopeptide extracts from B. amyloliquefaciens Pc3. In addition, the transcriptional levels of three lipopeptide synthesis genes, ituD , fenA , and srfA-A , and two fatty acid metabolism–related genes, FabI , which encodes enoyl-ACP reductase, and FadB , which encodes enoyl-CoA hydratase, were found to be upregulated in cells grown with exogenous alkanoic acids. Among the six alkanoic acids tested, those with odd carbon chain lengths had a greater effect on lipopeptide production, antifungal activity, and target gene upregulation than those with even carbon chain lengths. These results provide a practical approach for the efficient production of lipopeptides in Bacillus amyloliquefaciens Pc3.
研究领域:
微生物学
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植物病理学
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生物技术
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DOI
高影响因子
PROCESS BIOCHEMISTRY
·
2019
·
IF 2.883
Hong Zhou,Bailin Cong,Yongqi Tian,Yu He,Huanghao Yang
Three new cyclic lipopeptides (compounds 1–3) were isolated from Bacillus sp. SY27F, which collected from the deep-sea hydrothermal vent in the Indian Ocean. The planar structures of compounds 1–3 were characterized by LC–MS, GC–MS and NMR, whereas their absolute configurations were determined by modified Marfey’s analysis and optical rotation contrast. They shared the same heptapeptide chain (N-L-Gln 1 -D-Leu 2 -L-Leu 3 -L-Val 4 -L-Asp 5 -D-Leu 6 -L-Ile 7 -C), differing only by the length of the fatty acid chain. Compounds 1–3 displayed significant cytotoxic activity against DU145, MCF-7 and HepG2 cancer cell lines with IC 50 values of 96.8–190.7 nM and moderate to weak cytotoxicity against A549, HeLa and HT1080, with IC 50 values of 9.3–43.2 μM, respectively. However, none of the three compounds showed any antibacterial activity against Escherichia coli, Staphylococcus aureus and Monilia albicans .
研究领域:
微生物学
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药物化学
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海洋生物学
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DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2013
·Vol. 97
·期 21
·9525-9534
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IF 3.689
Zhang Xiaoyun,Li Baoqing,Wang Ye,Guo Qinggang,Lu Xiuyun,Li Shezeng,Ma Ping
Bacillus atrophaeus CAB-1 displays a high inhibitory activity against various fungal pathogens and suppresses cucumber powdery mildew and tomato gray mold. We extracted and identified lipopeptides and secreted proteins and volatile compounds produced by strain CAB-1 to investigate the mechanisms involved in its biocontrol performance. In vitro assays indicated all three types of products contributed to the antagonistic activity against the fungal pathogen Botrytis cinerea . Each of these components also effectively prevented the occurrence of the cucumber powdery mildew caused by Sphaerotheca fuliginea under greenhouse conditions. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry revealed that the major bioactive lipopeptide was fengycin A (C15–C17). We isolated the crude-secreted proteins of CAB-1 and purified a fraction with antifungal activity. This protein sequence shared a high identity with a putative phage-related pre-neck appendage protein, which has not been reported as an antifungal factor. The volatile compounds produced by CAB-1 were complex, including a range of alcohols, phenols, amines, and alkane amides. O -anisaldehyde represented one of the most abundant volatiles with the highest inhibition on the mycelial growth of B. cinerea . To our knowledge, this is the first report on profiling three types of antifungal substances in Bacilli and demonstrating their contributions to plant disease control.
研究领域:
植物病理学
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微生物学
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DOI
PubMed
高影响因子
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
·
2016
·Vol. 18
·期 15
·10129-10137
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IF 4.449
Sijia Wang,Yinxing Shen,Junqi Zhang,Shouhong Xu,Honglai Liu
Thermo-sensitive drug carriers are receiving increasing attention for use with localized hyperthermia at abnormal tissue sites or to easily implement hyperthermia. In this study, a thermo-sensitive lipopeptide was designed, consisting of a carbon chain and a leucine zipper with an amino acid sequence CH3-(CH2)4-CO-NH-VAQLEVK-VAQLESK-VSKLESK-VSSLESK-COOH. They could form dimers by the hydrophobic force at body temperature and separate into single random coils above the melting temperature (Tm). The lipopeptide was mixed with phospholipids to form a hybrid liposome (Lipo-LPe). The Tm of the free lipopeptide and lipopeptide in Lipo-LPe was found to be 48.0 °C and 42.5 °C from circular dichroism data, respectively. Compared with the pure liposome, the phase-transition temperature (Ttr) of Lipo-LPe, which was obtained by differential scanning calorimetry, was increased by about 5 °C, showing an improvement of thermal stability. The drug release rate of Lipo-LPe was slightly decreased at body temperature but greatly increased at mild hyperthermia in vitro. Drug release under intermittent heating was performed, and the reversibility of thermo-sensitive on/off switch was confirmed. Furthermore, Lipo-LPe achieved the maximum amount of cell death under mild hyperthermia. We concluded that Lipo-LPe, as a novel thermo-sensitive drug carrier, provides a promising opportunity for controlling drug release.
研究领域:
药剂学
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生物化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL CONTROL
·
2023
·
IF 4.2
Yu Ding,Fengjuan Liu,Jin Yang,Yingying Fan,Lvjian Yu,Zenghao Li,Na Jiang,Jing An,Ziwei Jiao,Cheng Wang
Penicillium expansum is the main causal organism of apple rot and causes huge economic losses during apple storage. Patulin (PAT) produced by P. expansum , occurs widely in apples and their products because of its water-solubility and thermal stability . In the present study, we isolated bacterial strains with antagonistic activity against P. expansum to effectively control the growth of P. expansum and production of PAT. We isolated a bacterium named YL-RY0310, which inhibited the growth of P. expansum and production of PAT in apples by 77.4% and 48.4%, respectively. Strain YL-RY0310 was 96% homologous to Bacillus mojavensis using morphological and 16S rRNA gene sequencing analyses. In addition, DNA amplification analysis using Bacillus -specific primers showed that the genes responsible for synthesis of lipopeptides of surfactin, iturins and fengycin are expressed. Oxford cup agar diffusion test showed that its crude lipopeptides could effectively inhibit the growth of P. expansum . Furthermore, strain YL-RY0310 could significantly degrade PAT; the degradation efficiencies of the intracellular and extracellular metabolites of the strain were 62.6% and 56.9%, respectively. Therefore, B. mojavensis YL-RY0310 could be used as a biocontrol agent to inhibit the growth of P. expansum and control PAT contamination in apples. This study provides a theoretical basis for a novel biological control strategy and degradation of mycotoxin.
研究领域:
植物病理学
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食品科学
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微生物学
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DOI
高影响因子
Small
·
2021
·Vol. 18
·期 3
·2104034
·
IF 13.281
Jiao Yang Lu,Wei Tao Huang,Kexuan Zhou,Xiaoli Zhao,Shuqing Yang,Liqiu Xia,Xuezhi Ding
Discovering new drugs and improving action mechanisms is a promising strategy to overcome chemotherapy ineffectiveness caused by cancer cell apoptosis resistance. Natural products (like cyclic lipopeptides, CLPs) are potential sources of nonapoptotic cell death inducers and can form diverse supramolecular structures, closely relating to their bioactivities. Herein, it is found for the first time that fatty chain is the key to maintain self-assembled form and antitumor activity of microbial-derived amphiphilic CLP bacillomycin Lb (B-Lb). Compared with B-Lb analogues assemblies without antitumor activity, B-Lb supramolecular self-assemblies (including nanomicelles, nanofibers, giant micrometer rods) can be generated in a multilevel and cross-scale manner and served as a methuosis-like cell death inducer triggered by cytoplasmic vacuolation through macropinocytosis in MDA-MB-231-Luc and MCF-7 cells and in vivo tumor-bearing mice. This study will promote constructing of customized CLP micro-/nanostructures with multipurposes and functions, and boost designing of new antitumor drugs as nonapoptotic cell death modulators based on structure–activity relationship.
研究领域:
药学
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生物技术
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癌症研究
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Yin Shi,Xiaoqian Feng,Liming Lin,Jing Wang,Jiaying Chi,Biyuan Wu,Guilin Zhou,Feiyuan Yu,Qian Xu,Daojun Liu,Guilan Quan,Chao Lu,Xin Pan,Jianfeng Cai,Chuanbin Wu
Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local “burst” release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6–6.3 μg mL −1 ), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.
研究领域:
生物医学工程
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药剂学
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微生物学
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DOI
PubMed
高影响因子
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