BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Shu-Qin Gao,Hong Yuan,Xin-Zhi Yang,Heng-Fang Xiang,Xiangshi Tan,Ge-Bo Wen,Ying-Wu Lin
Globins are heme proteins such as hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb), playing important roles in biological system. In addition to normal functions, zebrafish Ngb was able to penetrate cell membranes, whereas less was known for other globin members. In this study, to improve the cell-membrane-penetrating activity of globins, we used sperm whale Mb as a model protein and constructed a quadruple mutant of G5K/Q8K/A19K/V21K Mb (termed 4K Mb), by introduction of four positive charges on the protein surface , which was designed according to the amino acid alignment with that of zebrafish Ngb. Spectroscopic and crystallographic studies showed that the four positively charged Lys residues did not affect the protein structure. Cell-membrane-penetrating essay further showed that 4K Mb exhibited enhanced activity compared to that of native Mb. This study provides valuable information for the effect of distribution of charged residues on the protein structure and the cell-membrane-penetrating activity of globins. Therefore, it will guide the design of protein-based biomaterials for biological applications.
研究领域:
生物化学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yameng Wang,Zhiyuan Wang,Qibin Li,Yangjun Feng,Jinling Li,Yuxiang Lu,JingYing Zhang,Xue Ke
The special physiological barriers of women, such as vaginal mucus and self-cleaning behavior, pose great challenges for the treatment of vulvovaginal candidiasis ( VVC ), and the drug resistance caused by fungal biofilms limits the application of existing antifungal drugs. Based on this, we designed a “three-in-one” thermosensitive gel system (AF/BP Gel) loaded with antibiofilm nanoparticles (AF NPs) and mucus penetration-assisting nanoparticles (BP NPs) to achieve vaginal adhesion while enhancing mucus and biofilm penetration. AF NPs were loaded with farnesol (FAR) and amphotericin B (AMB), and FAR is one of quorum sensing molecules which can interfere with biofilm-related genes such as ALS3 , HWP1 , RAS1 , CPH1 , EFG1 , NRG1 , TUP1 , UME6 , and disperse mature biofilm, thus playing a synergic antibiofilm role with AMB. BP NPs was loaded with bromelain (BRO), which cleared the mucus barrier for AF NPs and help it penetrate deep into the infection. These two kinds of nanoparticles use the thermosensitive gel matrix to reach the surface of the vaginal mucosa uniformly and persistently to overcome the obstacle of vaginal self-cleaning. AF/BP Gel showed great anti- candida albicans activity in vitro and in vivo , and greatly improved the inflammatory conditions in VVC mice. Overall, this “three-in-one” thermosensitive gel system can overcome multiple physiological barriers and resist different periods of biofilm, providing a new platform for treating vagina-associated infections.
研究领域:
药剂学
·
微生物学
·
妇科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2019
·Vol. 19
·期 4
·1800364
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IF 2.895
Yang Ming,Yao Xiao,Yuan Tian,Shaobing Zhou
Considerable efforts have been devoted to enhancing the cell penetration of nanoparticles by coating cell-penetrating peptides (CPPs) on the surface. However, the internalization mechanism for a CPP at different concentrations varies a lot. It is acknowledged that the mechanism is restricted to endocytic pathway at relatively low concentrations; however, direct translocation becomes dominant at high concentrations. This raises an interesting question on how the surface Tat coating density of the nanoparticles would influence their cell–membrane interaction and the consequent internalization behavior. This study systematically investigates the effect of Tat peptides on the internalization behavior of polymeric micelles by tuning surface Tat coating density, incubation concentrations, incubation time, and other factors using poly(ethylene glycol)–poly(ε-caprolactone) copolymer (PEG-PCL) micelles. It is found that both energy-dependent and energy-independent pathways are involved in the cellular uptake process, and the Tat-conjugated polymeric micelles strongly accumulated on the cell surface at initial stage. The membrane-anchoring and internalization rate increase with the increasing Tat coating density. Furthermore, the increasing of Tat coating density accelerates the energy-independent pathway. It is envisioned that this finding will further shed light on the surface modification of nanoparticles for enhanced cell penetration and direct translocation into cell cytoplasm.
研究领域:
生物医学工程
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药剂学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Ping Xu,Libo Yuan,Ke Wang,Boyuan Pan,Yong Ye,Kui Lu
Two peptide-carbazole conjugates , CTAT and CNLS, were designed and synthesized using carbazole Schiff base to modify the cell membrane penetrating peptide TAT (47–57) and the nuclear localization peptide NLS at the N terminus . The interaction with ctDNA was investigated by multispectral and agarose gel electrophoresis . And the effects of CNLS and CTAT on the G-quadruplex structure were explored by circular dichroism titration experiments. The results show that both CTAT and CNLS interact with ctDNA in a minor groove binding manner. Both conjugates bind more tightly to DNA than the individual substances CIBA, TAT and NLS. In addition, CTAT and CNLS are capable of unfolding parallel G-quadruplex structures and are potential G-quadruplex unfolding agents. Finally, broth microdilution was performed to test the antimicrobial activity of the peptides. The results showed that CTAT and CNLS had a 4-fold increase in antimicrobial activity compared with the parent peptides TAT and NLS. They could exert antimicrobial activity by disrupting the integrity of cell membrane bilayer and binding to DNA, and could be used as novel antimicrobial peptides for the development of novel antimicrobial antibiotics.
研究领域:
生物化学
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分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
·
IF 3.65
Chaoran Xu,Wei He,Yaqi Lv,Chao Qin,Lingjia Shen,Lifang Yin
A prodrug-based nanosystem obtained by formulating prodrug and nanotechnology into a system is one of the most promising strategies to enhance drug delivery for disease treatment. Herein, we report a new nanosystem based on HA–PTX conjugates (HA–PTX Ns), which penetrated across cell membranes into cytosol, thus enhancing paclitaxel (PTX) delivery. HA–PTX Ns were successfully obtained based on HA–PTX, and their average particle size was approximately 200 nm. Importantly, unlike other prodrug-based nanosystems, HA–PTX Ns obtained cellular entry without entrapment within the lysosomal–endosomal system by using pathways including clathrin-mediated endocytosis, microtubule-associated internalization, macropinocytosis and cholesterol-dependence. Due to significant accumulation in tumors, HA–PTX Ns had more than a 4-fold decrease in tumor volume on day 14 in contrast with PTX alone. In conclusion, HA–PTX Ns could enter cells, bypass the lysosomal–endosomal system and improve PTX delivery.
研究领域:
药物递送
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肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2016
·
IF 5.583
Yuejing Xi,Tao Song,Songyao Tang,Nuosha Wang,Jianzhong Du
Traditional antibiotics usually sterilize in chemical ways, which may lead to serious drug resistance. By contrast, peptide-based antibacterial materials are less susceptible to drug resistance. Herein we report the preparation of an antibacterial peptide-based copolymer micelle and the investigation of its membrane-penetration antibacterial mechanism by transmission electron microscopy (TEM). The copolymer is poly(l-lactide)-block-poly(phenylalanine-stat-lysine) [PLLA31-b-poly(Phe24-stat-Lys36)], which is synthesized by ring-opening polymerization. The PLLA chains form the core, whereas the polypeptide chains form the coronas of the micelle in aqueous solution. This micelle boasts excellent antibacterial efficacy against both Gram-positive and Gram-negative bacteria. Furthermore, TEM studies clearly reveal that the micelles pierce and then destroy the cell membrane of the bacteria. We also compared the advantages and disadvantages of two general methods for measuring the Minimal Inhibitory Concentration (MIC) values of antibacterial micelles. Overall, this study provides us with direct evidence for the antibacterial mechanism of polypeptide-based micelles and a strategy for synthesizing biodegradable antibacterial nanomaterials without antibiotic resistance.
研究领域:
生物材料学
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微生物学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Fang Pan,Yueping Li,Yujie Ding,Songwei Lv,Rongrong You,Roja Hadianamrei,Mhd Anas Tomeh,Xiubo Zhao
Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells . In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Zhaoxu Meng,Liping Zhang,Zhonggui He,He Lian
The integration of noninvasive photodynamic therapy (PDT) and imaging in the gastrointestinal tract is extremely challenging because of the limited light penetration in traditional PDT, and physiological barriers such as inorganic salts and mucous layers. Herein, d-α-tocopherol polyethylene glycol 1000 succinate-succinic acid-mercapto-ethylamine (TPGS-SH) was used to functionalize upconverting nanoparticles (UCNPs) and endow the modified UCNPs@TPGS-SH nanoparticles with excellent hydrophilic properties, biocompatibility, gastrointestinal stability and mucus penetration. After loading the photosensitizer zinc phthalocyanine (ZnPC) onto UCNPs@TPGS-SH, the resulting nanosystem ZnPC-UCNPs@TPGS-SH converted near-infrared light (NIR) to visible light, which activated ZnPC to generate singlet oxygen that showed a strong killing effect in Caco-2 cells. In-situ mucosal penetration assay showed that ZnPC-UCNPs@TPGS-SH accumulated more in the enterocytes of duodenum, jejunum and ileum, and less in the mucosal layer compared to ZnPC-UCNPs@TPGS. Moreover, cellular uptake and in situ tracing experiments confirmed that the florescent light emitted by UCNPs upon upconversion of deep penetrating NIR light could also serve as an imaging probe. These findings demonstrate the promising potential of this theranostic nanosystem for simultaneous deep penetrating biological tracing and PDT in gastrointestinal cancer.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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药学科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Meng Ding,Wei Zhao,Xu Zhang,Lingjie Song,Shifang Luan
Bacterial biofilm is notorious for causing chronic infections, whose antibiotic treatment is bringing about severe multidrug resistance and environmental contamination. Stimuli-responsive nanocarriers have become encouraging materials to combat biofilm infections with high efficiency and low side effect. Herein, a charge-switchable and pH-responsive nanocomplex is fabricated via a facile aqueous one-pot zeolitic imidazolate framework-8 (ZIF-8) encapsulation of proteinase K (PK) and photosensitizer Rose Bengal (RB), for enzymatic and photodynamic therapies (PDT) against biofilm infections. Once encountering in acidic microenvironment, the surface charge of nanocomplex can switch self-adaptively from negative to positive, hence remarkably facilitating the biofilm penetration of nanocomplex. After acid-induced decomposition of nanocomplex, the released PK degrades biofilm matrix and loosens its structure, promoting diffusion of RB inside the biofilm. Afterwards, upon visible light illumination, the RB generates highly reactive oxygen species (ROS), which can readily and efficiently kill the remained bacteria even in the biofilm core. The charge-assisted penetration makes PK and RB fully functional, resulting in a cooperative effect concerning high biofilm eradication capacity, as testified by biofilm models both in vitro and in vivo . The green synthesis and good therapeutic performance of the nanocomplex manifests its considerable potential as a nontoxic and effective platform for biofilm treatment.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·
IF 15.1
Haibin Wu,Min Wei,Shen Hu,Pu Cheng,Shuhan Shi,Fan Xia,Lenan Xu,Lina Yin,Guang Liang,Fangyuan Li,Daishun Ling
Nanozymes, featuring intrinsic biocatalytic effects and broad-spectrum antimicrobial properties, are emerging as a novel antibiotic class. However, prevailing bactericidal nanozymes face a challenging dilemma between biofilm penetration and bacterial capture capacity, significantly impeding their antibacterial efficacy. Here, this work introduces a photomodulable bactericidal nanozyme (ICG@hMnO x ), composed of a hollow virus-spiky MnO x nanozyme integrated with indocyanine green, for dually enhanced biofilm penetration and bacterial capture for photothermal-boosted catalytic therapy of bacterial infections. ICG@hMnO x demonstrates an exceptional capability to deeply penetrate biofilms, owing to its pronounced photothermal effect that disrupts the compact structure of biofilms. Simultaneously, the virus-spiky surface significantly enhances the bacterial capture capacity of ICG@hMnO x . This surface acts as a membrane-anchored generator of reactive oxygen species and a glutathione scavenger, facilitating localized photothermal-boosted catalytic bacterial disinfection. Effective treatment of methicillin-resistant Staphylococcus aureus -associated biofilm infections is achieved using ICG@hMnO x , offering an appealing strategy to overcome the longstanding trade-off between biofilm penetration and bacterial capture capacity in antibacterial nanozymes. This work presents a significant advancement in the development of nanozyme-based therapies for combating biofilm-related bacterial infections.
研究领域:
纳米技术
·
生物医学工程
·
抗菌治疗
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生物材料
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ye Zhao,Yao Liu,Ran Liao,Pan Ran,Yuan Liu,Zixuan Li,Jichun Shao,Long Zhao
Sonodynamic therapy offers a highly accurate treatment for bacterial infections; however, its antibacterial efficacy is hindered by bacterial biofilms that limit the penetration of sonosensitizers. Herein, a nitric oxide (NO)-driven mushroom-like Janus nanomotor (BT@PDA-La) based on the unilateral coating of polydopamine (PDA) on piezoelectric tetragonal barium titanate (BT) and further modified with l-arginine (l-Arg) on the PDA side is fabricated. In the infected microenvironment with high levels of H2O2, NO is produced unilaterally from BT@PDA-La, thus leading to its self-propelled movement and facilitating its permeability in the biofilm. Under ultrasonic vibrations, the piezoelectric effect of BT@PDA-La is triggered by the exogenous mechanical wave, and toxic reactive oxygen species (ROS) are efficiently generated via an in situ catalytic reaction. The synergistic treatment with ROS/NO achieved the destruction of biofilms and embedded drug-resistant bacteria in vitro. Importantly, BT@PDA-La exhibits excellent biofilm penetration capacity, effectively eliminating biofilm infection while accelerating the healing of infected muscles by alleviating oxidative stress, regulating inflammatory factors, and accelerating angiogenesis. Collectively, this study provides a promising strategy for enhancing the penetration of pathological environment-driven nanomaterials through biofilms and advances the application of nanomotors for the therapy of bacterial infections in clinical medicine.
研究领域:
纳米技术
·
生物医学工程
·
微生物学
·
治疗药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Bing Cao,Jian Zhang,Yingfei Ma,Yanan Wang,Yun li,Ruixue Wang,Donghai Cao,Yongzhen Yang,Ruiping Zhang
Periodontitis is the leading cause of adult tooth missing. Thorny bacterial biofilm and high reactive oxygen species (ROS) levels in tissue are key elements for the periodontitis process. It is meaningful to develop an advanced therapeutic system with sequential antibacterial/ antioxidant ability to meet the overall goals of periodontitis therapy. Herein, a dual-polymer functionalized melanin-AgNPs (P/D-MNP-Ag) with biofilm penetration, hydroxyapatite binding, and sequentially treatment ability are fabricated. Polymer enriched with 2-(Dimethylamino)ethyl methacrylate (D), can be protonated in an acid environment with enhanced positive charge, promoting penetration in biofilm. The other polymer is rich in phosphate group (P) and can chelate Ca 2+ , promoting the polymer to adhere to the hydroxyapatite surface. Melanin has good ROS scavenging and photothermal abilities, after in situ reduction Ag, melanin-AgNPs composite has sequentially transitioned between antibacterial and antioxidative ability due to heat and acid accelerated Ag + release. The released Ag + and heat have synergistic antibacterial effects for bacterial killing. With Ag + consumption, the antioxidant ability of MNP recovers to scavenge ROS in the inflammatory area. When applied in the periodontitis model, P/D-MNP-Ag has good therapeutical effects to ablate biofilm, relieve inflammation state, and reduce alveolar bone loss. P/D-MNP-Ag with sequential treatment ability provides a reference for developing advanced oral biofilm eradication systems.
研究领域:
材料科学
·
纳米技术
·
牙科科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）