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Biophysical Journal Apr 2018Biomolecules exist and function in cellular microenvironments that control their spatial organization, local concentration, and biochemical reactivity. Due to the...
Biomolecules exist and function in cellular microenvironments that control their spatial organization, local concentration, and biochemical reactivity. Due to the complexity of native cytoplasm, the development of artificial bioreactors and cellular mimics to compartmentalize, concentrate, and control the local physico-chemical properties is of great interest. Here, we employ self-assembling polypeptide coacervates to explore the partitioning of the ubiquitous cytoskeletal protein actin into liquid polymer-rich droplets. We find that actin spontaneously partitions into coacervate droplets and is enriched by up to ∼30-fold. Actin polymerizes into micrometer-long filaments and, in contrast to the globular protein BSA, these filaments localize predominately to the droplet periphery. We observe up to a 50-fold enhancement in the actin filament assembly rate inside coacervate droplets, consistent with the enrichment of actin within the coacervate phase. Together these results suggest that coacervates can serve as a versatile platform in which to localize and enrich biomolecules to study their reactivity in physiological environments.
Topics: Actins; Cytoskeleton; Peptides; Polylysine; Protein Multimerization; Protein Structure, Quaternary
PubMed: 29642033
DOI: 10.1016/j.bpj.2018.02.020 -
Biomedicine & Pharmacotherapy =... Jun 2023Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive...
Drug delivery systems require that carrier materials have good biocompatibility, degradability, and constructability. Poly(amino acids), a substance with a distinctive secondary structure, not only have the basic features of the carrier materials but also have several reactive functional groups in the side chain, which can be employed as drug carriers to deliver anticancer drugs. The conformation of isomers of drug carriers has some influence on the preparation, morphology, and efficacy of nanoparticles. In this study, two isomers of polylysine, including ε-polylysine (ε-PL) and α-polylysine (α-PL), were used as drug carriers to entrap methotrexate (MTX) and construct nano-drug delivery systems. ε-PL/MTX nanoparticles with the morphology of helical nanorods presented a small particle size (115.0 nm), and relative high drug loading content (57.8 %). The anticancer effect of ε-PL/MTX nanoparticles was 1.3-fold and 2.6-fold stronger than that of α-PL/MTX nanoparticles in vivo and in vitro, respectively. ε-PL is an ideal drug carrier with potential clinical application prospects.
Topics: Methotrexate; Polylysine; Antineoplastic Agents; Drug Carriers; Nanoparticles
PubMed: 37037095
DOI: 10.1016/j.biopha.2023.114662 -
Contrast Media & Molecular Imaging 2016Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful...
Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI.
Topics: Animals; Astrocytes; Cell Line, Tumor; Connexin 43; Contrast Media; Gadolinium DTPA; Glioma; Humans; Magnetic Resonance Imaging; Polylysine; Radiography; Rats
PubMed: 26265140
DOI: 10.1002/cmmi.1653 -
ACS Combinatorial Science Apr 2017Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched...
Cationic macromolecular carriers can be effective carriers for small molecular compounds, drugs, epitopes, or nucleic acids. Polylysine-based polymeric branched polypeptides have been systematically studied on the level of cells and organisms as well. In the present study, we report our findings on the cellular uptake characteristics of nine structurally related polylysine-based polypeptides with cationic side chains composed of (i) single amino acid (poly[Lys(X)], XK) or (ii) oligo[dl-alanine] (poly[Lys(dl-Ala)], AK) or (iii) oligo[dl-alanine] with an additional amino acid (X) at the terminal position (poly[Lys(X-dl-Ala)] (XAK)) or (iv) at the position next to the polylysine backbone (poly[Lys(dl-Ala-X)] (AXK)). In vitro cytotoxicity and cellular uptake were characterized on HT-29 human colon carcinoma and HepG2 human hepatocarcinoma cell lines. Data indicate that the polycationic polypeptides studied are essentially nontoxic in the concentration range studied, and their uptake is very much dependent on the side chain structure (length, identity of amino acid X, and distance between the terminal positive charges) and also on the cell lines. Our findings in uptake inhibition studies suggest that predominantly macropinocytosis and caveole/lipid raft mediated endocytosis are involved. The efficacy of their internalization is markedly influenced by the hydrophobicity and charge properties of the amino acid X. Interestingly, the uptake properties of the these polypeptides show certain similarities to the entry pathways of several cell penetrating peptides.
Topics: Cations; Cell Line, Tumor; Drug Delivery Systems; Endocytosis; Humans; Peptides; Polylysine; Protein Conformation; Structure-Activity Relationship
PubMed: 28276242
DOI: 10.1021/acscombsci.6b00133 -
Clinical Cancer Research : An Official... Oct 2018Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and...
Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells. In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and blood. Two patients completed 2 cycles of IT treatments, and 1 achieved clinical benefit (stable disease, progression-free survival 6 months), whereas the remainder had progressive disease. Poly-ICLC was well tolerated, with principal side effects of fatigue and inflammation at injection site (
Topics: Aged; Biopsy; Carboxymethylcellulose Sodium; Drug Administration Schedule; Female; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; Immunologic Factors; Immunomodulation; Injections, Intralesional; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Pilot Projects; Poly I-C; Polylysine; Prognosis; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 29950349
DOI: 10.1158/1078-0432.CCR-17-1866 -
International Journal of Nanomedicine 2007Microbicides are compounds that applied vaginally or rectally, protect the user from sexually transmitted infections. Although no commercial product is yet available,... (Review)
Review
Microbicides are compounds that applied vaginally or rectally, protect the user from sexually transmitted infections. Although no commercial product is yet available, many candidates are under development. A leading candidate, VivaGel (SPL7013 Gel) is the product of nanotechnology. The active ingredient is SPL7013, a dendrimer that was designed specifically with HIV and HSV antiviral activity and human safety in mind. SPL7013 has demonstrated efficacy against human immunodeficiency virus and herpes simplex virus in in vitro and animal models. VivaGel appears to be well tolerated in both animals and humans. This review summarizes the studies of VivaGel and its active ingredient, SPL7013.
Topics: Anti-Infective Agents, Local; Antiviral Agents; Clinical Trials as Topic; Dendrimers; HIV Infections; Herpes Simplex; Humans; Polylysine
PubMed: 18203424
DOI: No ID Found -
International Journal of Nanomedicine 2020Celastrol (CEL), a triterpene extracted from the Chinese herb , has been reported to have profound anticancer activities. However, poor water solubility and high side...
BACKGROUND
Celastrol (CEL), a triterpene extracted from the Chinese herb , has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL.
PURPOSE
We proposed a facile "in situ drug conjugation-induced self-assembly" strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma.
METHODS
First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)--poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model.
RESULTS
The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL.
CONCLUSION
In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.
Topics: Animals; Antineoplastic Agents, Phytogenic; Delayed-Action Preparations; Dynamic Light Scattering; Hydrophobic and Hydrophilic Interactions; Male; Melanoma; Melanoma, Experimental; Mice, Inbred C57BL; Micelles; Microscopy, Electron, Transmission; Nanoparticles; Pentacyclic Triterpenes; Polyethylene Glycols; Polylysine; Triterpenes
PubMed: 32110017
DOI: 10.2147/IJN.S232603 -
Molecules (Basel, Switzerland) May 2023Thin oxide layers form easily on the surfaces of titanium (Ti) components, with thicknesses of <100 nm. These layers have excellent corrosion resistance and good...
Thin oxide layers form easily on the surfaces of titanium (Ti) components, with thicknesses of <100 nm. These layers have excellent corrosion resistance and good biocompatibility. Ti is susceptible to bacterial development on its surface when used as an implant material, which reduces the biocompatibility between the implant and the bone tissue, resulting in reduced osseointegration. In the present study, Ti specimens were surface-negatively ionized using a hot alkali activation method, after which polylysine and polydopamine layers were deposited on them using a layer-by-layer self-assembly method, then a quaternary ammonium salt (QAS) (EPTAC, DEQAS, MPA-N) was grafted onto the surface of the coating. In all, 17 such composite coatings were prepared. Against and , the bacteriostatic rates of the coated specimens were 97.6 ± 2.0% and 98.4 ± 1.0%, respectively. Thus, this composite coating has the potential to increase the osseointegration and antibacterial performance of implantable Ti devices.
Topics: Titanium; Polylysine; Coated Materials, Biocompatible; Anti-Bacterial Agents; Escherichia coli; Ammonium Compounds; Surface Properties
PubMed: 37241863
DOI: 10.3390/molecules28104120 -
International Journal of Molecular... Mar 2023Polyethylene--polypeptide copolymers are biologically interesting, but studies of their synthesis and properties are very few. This paper reports synthesis and...
Polyethylene--polypeptide copolymers are biologically interesting, but studies of their synthesis and properties are very few. This paper reports synthesis and characterization of well-defined amphiphilic polyethylene--poly(L-lysine) (PE--PLL) block copolymers by combining nickel-catalyzed living ethylene polymerization with controlled ring-opening polymerization (ROP) of ε-benzyloxycarbonyl-L-lysine--carboxyanhydride (Z-Lys-NCA) and sequential post-functionalization. Amphiphilic PE--PLL block copolymers self-assembled into spherical micelles with a hydrophobic PE core in aqueous solution. The pH and ionic responsivities of PE--PLL polymeric micelles were investigated by means of fluorescence spectroscopy, dynamic light scattering, UV-circular dichroism, and transmission electron microscopy. The variation of pH values led to the conformational alteration of PLL from α-helix to coil, thereby changing the micelle dimensions.
Topics: Micelles; Polylysine; Polyethylene; Polymers; Peptides; Polyethylene Glycols
PubMed: 36982576
DOI: 10.3390/ijms24065495 -
The Journal of Reproduction and... Oct 2022In this study, we cryopreserved pig spermatozoa using carboxylated poly-L-lysine (CPLL) as the cryoprotectant to determine its efficacy. Pig spermatozoa were placed in a...
In this study, we cryopreserved pig spermatozoa using carboxylated poly-L-lysine (CPLL) as the cryoprotectant to determine its efficacy. Pig spermatozoa were placed in a freezing extender containing 3% (v/v) glycerol and different CPLL concentrations. The motility indices of the spermatozoa cryopreserved with 0.25% (v/v) CPLL at 6 (59.3), 9 (53.7), and 12 (26.2) h after thawing were significantly higher (P < 0.01 or P < 0.05) than those of the spermatozoa cryopreserved without CPLL (53.7, 40.1, and 17.5 at 6, 9, and 12 h after thawing, respectively). The concentration of CPLL in the freezing extender did not affect the ability of frozen-thawed spermatozoa to fertilize oocytes in vitro. However, the blastocyst formation rate of embryos derived from spermatozoa cryopreserved with 0.25% CPLL (24.6%) was significantly higher (P < 0.01) than that of embryos derived from spermatozoa cryopreserved without CPLL (11.2%). The conception rate of the sows inseminated with spermatozoa cryopreserved with 0.25% CPLL (72.2%) was not significantly different from that of the sows inseminated with spermatozoa stored at 17°C (81.3%). However, the mean number of total piglets born to the former (10.0) was significantly lower (P < 0.05) than that of total piglets born to the latter (13.4). The results showed that CPLL in the freezing extender maintained the motility of frozen-thawed pig spermatozoa and improved the in vitro development of embryos produced by in vitro fertilization. In addition, we have demonstrated that piglets could be obtained with artificial insemination using spermatozoa cryopreserved with CPLL.
Topics: Animals; Cryopreservation; Cryoprotective Agents; Female; Glycerol; Male; Polylysine; Semen Preservation; Sperm Motility; Spermatozoa; Swine
PubMed: 35908977
DOI: 10.1262/jrd.2022-058