An uPA cleavable conjugate of a recombinant αvβ3 targeting toxin and its bioactivity

Zhu, Wen; Zhou, Yu; Sun, Daolai

doi:10.1007/s11274-010-0491-7

Cited by 4 publications

(3 citation statements)

References 34 publications

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“…In an effort to reduce hemolysis, the melittin sequence has been altered in some studies. − However, these alterations led to decreased membrane activity in cancer cells . Other efforts have included conjugating melittin to an antibody or a targeting protein to increase the cancer cell specificity. , However, most melittin bioconjugates reported to date retain significant hemolytic activities, preventing them from being administered intravenously.…”

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confidence: 99%

Hybrid Melittin Cytolytic Peptide-Driven Ultrasmall Lipid Nanoparticles Block Melanoma Growth in Vivo

et al. 2013

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The cytolytic peptide melittin is a potential anticancer candidate that may be able to overcome tumor drug resistance due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, which is especially pronounced following intravenous administration. Here, we designed a hybrid cytolytic peptide, α-melittin, in which the N-terminus of melittin is linked to the C-terminus of an amphipathic α-helical peptide (α-peptide) via a GSG linker. The strong α-helical configuration allows α-melittin to interact with phospholipids and self-assemble into lipid nanoparticles, with a high efficiency for α-melittin encapsulation (>80%) and a strong ability to control the structure of the nanoparticle (~20 nm). This α-melittin-based lipid nanoparticle (α-melittin-NP) efficiently shields the positive charge of melittin (18.70 ± 0.90 mV) within the phospholipid monolayer, resulting in the generation of a neutral nanoparticle (2.45 ± 0.56 mV) with reduced cytotoxicity and a widened safe dosage range. Confocal imaging data confirmed that α-melittin peptides were efficiently released from the nanoparticles and were cytotoxic to the melanoma cells. Finally, α-melittin-NPs were administered to melanoma-bearing mice via intravenous injection. The growth of the melanoma cells was blocked by the α-melittin-NPs, with an 82.8% inhibition rate relative to the PBS-treated control group. No side effects of treatment were found in this study. Thus, the excellent properties of α-melittin-NP give it potential clinical applications in solid tumor therapeutics through intravenous administration.

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confidence: 99%

Hybrid Melittin Cytolytic Peptide-Driven Ultrasmall Lipid Nanoparticles Block Melanoma Growth in Vivo

et al. 2013

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“…However, very low concentrations of melittin can induce hemolytic side effects after intravenous injection, which severely limits in vivo applications. Many efforts have been made to modify the melittin sequence to reduce the hemolysis [ 39 – 41 ]. C. Huang et al developed an ultra-small size of melittin nanoparticles (α-melittin-NP) [ 28 ], α-melittin-NP can not only be effectively shielded the hemolytic properties by the phospholipid layer, but also has a great ability to directly kill melanoma cells, specifically activate liver sinusoidal endothelial cells and APCs in LNs [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Effective treatment of metastatic sentinel lymph nodes by dual-targeting melittin nanoparticles

Dai,

Yu,

Leng

et al. 2023

J Nanobiotechnol

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Sentinel lymph node (SLN) metastasis is an important promoter of distant metastasis in breast cancer. Therefore, the timely diagnosis and precise treatment are crucial for patient staging and prognosis. However, the simultaneous diagnosis of metastasis and the implementation of imaging-guided SLN therapy is challenging. Here, we report a melittin-loaded and hyaluronic acid (HA)-conjugated high-density lipoprotein (HDL) mimic phospholipid scaffold nanoparticle (MLT-HA-HPPS), which dually-target to both breast cancer and its SLN and efficiently inhibit SLN metastasis in the LN metastasis model. The melittin peptide was successfully loaded onto HA-HPPS via electrostatic interactions, and MLT-HA-HPPS possesses effective cytotoxicity for breast cancer 4T1 cells. Moreover, the effective delivery of MLT-HA-HPPS from the primary tumor into SLN is monitored by NIR fluorescence imaging, which greatly benefits the prognosis and treatment of metastatic SLNs. After paracancerous administration, MLT-HA-HPPS can efficiently inhibit primary tumor growth with an inhibition rate of 81.3% and 76.5% relative to the PBS-treated control group and HA-HPPS group, respectively. More importantly, MLT-HA-HPPS can effectively inhibit the growth of the metastatic SLNs with an approximately 78.0%, 79.1%, and 64.2% decrease in SLNs weight than those in PBS, HA-HPPS, and melittin-treated mice, respectively. Taken together, the MLT-HA-HPPS may provide an encouraging theranostic of SLN drug delivery strategy to inhibit primary tumor progression and prevent SLN metastasis of breast cancer. Graphical Abstract

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“…The phenotypes of the mutant strains were characterized by hemolytic activity, extracellular protease (ECPase) activity, and biofilm formation. Hemolytic and ECPase activity were assayed as previously described (23, 24). Biofilm formation was measured using crystal violet staining (25).…”

Section: Methodsmentioning

confidence: 99%

Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates

Wang

Ali

et al. 2019

Front. Immunol.

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In our previous study, several iron-related outer membrane proteins in Aeromonas hydrophila , a serious pathogen of farmed fish, conferred high immunoprotectivity to fish, and were proposed as potential vaccine candidates. However, the protective efficacy of these extracellular proteins against A. hydrophila remains largely unknown. Here, we identified secreted proteins that were differentially expressed in A. hydrophila LP-2 in response to iron starvation using an iTRAQ-based quantitative proteomics method. We identified 341 proteins, of which 9 were upregulated in response to iron starvation and 24 were downregulated. Many of the differently expressed proteins were associated with protease activity. We confirmed our proteomics results with Western blotting and qPCR. We constructed three mutants by knocking out three genes encoding differentially expressed proteins (Δ orf01830 , Δ orf01609 , and Δ orf03641 ). The physiological characteristics of these mutants were investigated. In all these mutant strains, protease activity decreased, and Δ orf01609 , and Δ orf01830 were less virulent in zebrafish. This indicated that the proteins encoded by these genes may play important roles in bacterial infection. We next evaluated the immune response provoked by the six iron-related recombinant proteins (ORF01609, ORF01830, ORF01839, ORF02943, ORF03355, and ORF03641) in zebrafish as well as the immunization efficacy of these proteins. Immunization with these proteins significantly increased the zebrafish immune response. In addition, the relative percent survival (RPS) of the immunized zebrafish was 50–80% when challenged with three virulent A. hydrophila strains, respectively. Thus, these extracellular secreted proteins might be effective vaccine candidates against A. hydrophila infection in fish.

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An uPA cleavable conjugate of a recombinant αvβ3 targeting toxin and its bioactivity

Cited by 4 publications

References 34 publications

Hybrid Melittin Cytolytic Peptide-Driven Ultrasmall Lipid Nanoparticles Block Melanoma Growth in Vivo

Hybrid Melittin Cytolytic Peptide-Driven Ultrasmall Lipid Nanoparticles Block Melanoma Growth in Vivo

Effective treatment of metastatic sentinel lymph nodes by dual-targeting melittin nanoparticles

Comparative Extracellular Proteomics of Aeromonas hydrophila Reveals Iron-Regulated Secreted Proteins as Potential Vaccine Candidates

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