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International Journal of Molecular... Nov 2022AQEE-30 is one of the VGF peptides, which are derived from the VGF polypeptide precursor, and related to various physiological phenomena including neuroprotective...
AQEE-30 is one of the VGF peptides, which are derived from the VGF polypeptide precursor, and related to various physiological phenomena including neuroprotective effects in Huntington's disease and amyotrophic lateral sclerosis (ALS). Although various functions of AQEE-30 have been reported so far, the structure of this peptide has not been reported yet. In this study, the structure of human AQEE-30 was investigated in hexafluoroisopropanol (HFIP) and dodecyl phosphocholine (DPC) micelle solutions, using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. CD results showed that AQEE-30 had a partial helical structure in aqueous buffer, and the helical structure was stabilized in the HFIP and DPC micelle solutions. The 3D structures determined by NMR spectroscopy showed that AQEE-30 adopted mainly α-helical structure in both the HFIP and DPC micelle solutions. The surface of AQEE-30 showed that it was predominantly negatively charged. The residues from 601 to 611 in both the HFIP and DPC micelle solutions showed amphiphilicity with four negatively charged residues, glutamate. The C-terminal consecutive arginine residues formed a partial positively charged surface. These results suggest an α-helical active structure of AQEE-30 in the cell-membrane environment.
Topics: Humans; Micelles; Neuropeptides; Circular Dichroism; Membranes; Peptides; Nerve Growth Factors
PubMed: 36430431
DOI: 10.3390/ijms232213953 -
Biomacromolecules May 2021Secondary structure formation differentiates polypeptides from most of the other synthetic polymers, and the transitions from random coils to rod-like α-helices or...
Secondary structure formation differentiates polypeptides from most of the other synthetic polymers, and the transitions from random coils to rod-like α-helices or β-sheets represent an additional parameter to direct self-assembly and the morphology of nanostructures. We investigated the influence of distinct secondary structures on the self-assembly of reactive amphiphilic polypept(o)ides. The individual morphologies can be preserved by core cross-linking via chemoselective disulfide bond formation. A series of thiol-responsive copolymers of racemic polysarcosine--poly(-ethylsulfonyl-dl-cysteine) (pSar--p(dl)Cys), enantiopure polysarcosine--poly(-ethylsulfonyl-l-cysteine) (pSar--p(l)Cys), and polysarcosine--poly(-ethylsulfonyl-l-homocysteine) (pSar--p(l)Hcy) was prepared by -carboxyanhydride polymerization. The secondary structure of the peptide segment varies from α-helices (pSar--p(l)Hcy) to antiparallel β-sheets (pSar--p(l)Cys) and disrupted β-sheets (pSar--p(dl)Cys). When subjected to nanoprecipitation, copolymers with antiparallel β-sheets display the strongest tendency to self-assemble, whereas disrupted β-sheets hardly induce aggregation. This translates to worm-like micelles, solely spherical micelles, or ellipsoidal structures, as analyzed by atomic force microscopy and cryogenic transmission electron microscopy, which underlines the potential of secondary structure-driven self-assembly of synthetic polypeptides.
Topics: Micelles; Polymerization; Polymers; Protein Structure, Secondary; Sulfhydryl Compounds
PubMed: 33830742
DOI: 10.1021/acs.biomac.1c00253 -
International Journal of Molecular... Jan 2023Nucleic acids have become important building blocks in nanotechnology over the last 30 years. DNA and RNA can sequentially build specific nanostructures, resulting in... (Review)
Review
Nucleic acids have become important building blocks in nanotechnology over the last 30 years. DNA and RNA can sequentially build specific nanostructures, resulting in versatile drug delivery systems. Self-assembling amphiphilic nucleic acids, composed of hydrophilic and hydrophobic segments to form micelle structures, have the potential for cancer therapeutics due to their ability to encapsulate hydrophobic agents into their core and position functional groups on the surface. Moreover, DNA or RNA within bio-compatible micelles can function as drugs by themselves. This review introduces and discusses nucleic acid-based spherical micelles from diverse amphiphilic nucleic acids and their applications in cancer therapy.
Topics: Humans; Micelles; Nucleic Acids; Drug Delivery Systems; RNA; DNA; Neoplasms; Hydrophobic and Hydrophilic Interactions
PubMed: 36675110
DOI: 10.3390/ijms24021592 -
Acta Biomaterialia Sep 2020Cabazitaxel, a novel tubulin inhibitor with poor affinity for P-glycoprotein, is a second-generation taxane holding great promise for the treatment of metastatic...
Cabazitaxel, a novel tubulin inhibitor with poor affinity for P-glycoprotein, is a second-generation taxane holding great promise for the treatment of metastatic castration-resistant prostate cancer. However, its poor solubility and lack of target-ability limit its therapeutic applications. Herein, we develop a biodegradable, enzyme-responsive, and targeted polymeric micelle for cabazitaxel. The micelle is formed from two amphiphilic block copolymers. The first block copolymer consists of PEG, an enzyme-responsive peptide, and cholesterol; whereas the second block copolymer consists of a targeting ligand, PEG and cholesterol. The enzyme-responsive peptide is cleavable in the presence of matrixmetaloproteinase-2 (MMP-2), which is overexpressed in the tumor microenvironment of prostate cancer. The micelle showed a very low critical micelle concentration (CMC), high drug loading, and high entrapment efficiency. Release of cabazitaxel from the micelle is dependent on the cleavage of the enzyme-responsive peptide. Moreover, the micelle showed dramatically higher cellular uptake in prostate cancer cells compared to free cabazitaxel. Importantly, the ligand-coupled polymeric micelle demonstrated better inhibition of tumor growth in mice bearing prostate cancer xenografts compared to unmodified micelle and free cabazitaxel. Taken together, these findings suggest that the enzyme-responsive cabazitaxel micelle is a potent and promising drug delivery system for advanced prostate cancer therapy. STATEMENT OF SIGNIFICANCE: Herein, we develop a biodegradable, enzyme-responsive, and actively targeted polymer micelle for cabazitaxel, which is a novel tubulin inhibitor with poor affinity for P-glycoprotein. Despite cabazitaxel's great promise for metastatic castration-resistant prostate cancer, its poor solubility, lack of target-ability, and high systemic toxicity limit its therapeutic applications, and therefore a targeted delivery system is highly needed for cabazitaxel. Our results demonstrate the importance of active targeting in targeted prostate cancer therapy. Encapsulating cabazitaxel in the micelle increases its activity and is expected to reduce its systemic toxicity, which is a major hurdle in its clinical applications. Moreover, the polymeric micelle may servers as a promising nanoscale platform for the targeted delivery of other chemotherapeutic agents to prostate cancer.
Topics: Animals; Cell Line, Tumor; Humans; Male; Mice; Micelles; Polymers; Prostatic Neoplasms; Taxoids; Tumor Microenvironment
PubMed: 32562805
DOI: 10.1016/j.actbio.2020.06.019 -
Biochimica Et Biophysica Acta.... Sep 2022Non-ionic detergents are important tools for the investigation of interactions between membrane proteins and lipid membranes. Recent studies led to the question as to...
Non-ionic detergents are important tools for the investigation of interactions between membrane proteins and lipid membranes. Recent studies led to the question as to whether the ability to capture protein-lipid interactions depends on the properties of detergents or their concentration in purification buffers. To address this question, we present the synthesis of an asymmetric, hybrid detergent that combines the head groups of detergents with opposing delipidating properties. We discuss detergent properties and protein purification outcomes to reveal whether the properties of detergent micelles or the detergent concentration in purification buffers drive membrane protein delipidation. We anticipate that our findings will enable the development of rationally design detergents for future applications in membrane protein research.
Topics: Detergents; Lipids; Membrane Proteins; Micelles
PubMed: 35551920
DOI: 10.1016/j.bbamem.2022.183958 -
Molecules (Basel, Switzerland) Jan 2023Dextran is by far one of the most interesting non-toxic, bio-compatible macromolecules, an exopolysaccharide biosynthesized by lactic acid bacteria. It has been... (Review)
Review
Dextran is by far one of the most interesting non-toxic, bio-compatible macromolecules, an exopolysaccharide biosynthesized by lactic acid bacteria. It has been extensively used as a major component in many types of drug-delivery systems (DDS), which can be submitted to the next in-vivo testing stages, and may be proposed for clinical trials or pharmaceutical use approval. An important aspect to consider in order to maintain high DDS' biocompatibility is the use of dextran obtained by fermentation processes and with a minimum chemical modification degree. By performing chemical modifications, artefacts can appear in the dextran spatial structure that can lead to decreased biocompatibility or even cytotoxicity. The present review aims to systematize DDS depending on the dextran type used and the biologically active compounds transported, in order to obtain desired therapeutic effects. So far, pure dextran and modified dextran such as acetalated, oxidised, carboxymethyl, diethylaminoethyl-dextran and dextran sulphate sodium, were used to develop several DDSs: microspheres, microparticles, nanoparticles, nanodroplets, liposomes, micelles and nanomicelles, hydrogels, films, nanowires, bio-conjugates, medical adhesives and others. The DDS are critically presented by structures, biocompatibility, drugs loaded and therapeutic points of view in order to highlight future therapeutic perspectives.
Topics: Dextrans; Drug Delivery Systems; Liposomes; Micelles; Nanoparticles
PubMed: 36770753
DOI: 10.3390/molecules28031086 -
International Journal of Molecular... Oct 2022Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining... (Review)
Review
Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining the benefits of polymeric micelles and magnetic nanoparticles within a single bioinstructive system. MPMs are formed by the self-assembly of polymer amphiphiles above the critical micelle concentration, generating a colloidal structure with a hydrophobic core and a hydrophilic shell incorporating magnetic particles (MNPs) in one of the segments. MPMs have been investigated most prominently as contrast agents for magnetic resonance imaging (MRI), as heat generators in hyperthermia treatments, and as magnetic-susceptible nanocarriers for the delivery and release of therapeutic agents. The versatility of MPMs constitutes a powerful route to ultrasensitive, precise, and multifunctional diagnostic and therapeutic vehicles for the treatment of a wide range of pathologies. Although MPMs have been significantly explored for MRI and cancer therapy, MPMs are multipurpose functional units, widening their applicability into less expected fields of research such as bioengineering and regenerative medicine. Herein, we aim to review published reports of the last five years about MPMs concerning their structure and fabrication methods as well as their current and foreseen expectations for advanced biomedical applications.
Topics: Contrast Media; Drug Delivery Systems; Hyperthermia, Induced; Micelles; Polymers; Precision Medicine
PubMed: 36233094
DOI: 10.3390/ijms231911793 -
Analytical Chemistry Jun 2018Creating new functional building blocks that expand the versatility of nanostructures depends on bottom-up self-assembly of amphiphilic biomolecules. Inspired by the...
Creating new functional building blocks that expand the versatility of nanostructures depends on bottom-up self-assembly of amphiphilic biomolecules. Inspired by the unique physicochemical properties of hydrophobic perfluorocarbons, coupled with the powerful functions of nucleic acids, we herein report the synthesis of a series of diperfluorodecyl-DNA conjugates (PF-DNA) which can efficiently self-assemble into micelles in aqueous solution. On the basis of the micelle structure, both target binding affinity and enzymatic resistance of the DNA probe can be enhanced. In addition, based on the hydrophobic effect, the PF-DNA micelles (PFDM) can actively anchor onto the cell membrane, offering a promising tool for cell-surface engineering. Finally, the PFDM can enter cells, which is significant for designing carriers for intracellular delivery. The combined advantages of the DNA micelle structure and the unique physicochemical properties of perfluorocarbons make these PFDM promising for applications in bioimaging and biomedicine.
Topics: DNA; Fluorocarbons; Halogenation; Micelles; Molecular Structure
PubMed: 29770690
DOI: 10.1021/acs.analchem.8b01005 -
Biomedicine & Pharmacotherapy =... Oct 2023The purpose of this study was to examine the effects of nano-micelle curcumin (NMC)-induced redox imbalance on mitochondrial biogenesis and mitophagy. For this purpose,...
The purpose of this study was to examine the effects of nano-micelle curcumin (NMC)-induced redox imbalance on mitochondrial biogenesis and mitophagy. For this purpose, 24 mature male Wistar rats were divided into control and NMC-received groups (7.5, 15, and 30 mg/kg) groups. After 48 days, the Nrf1, Nrf2, and SOD (Cu/Zn) expression levels, as well as GSH/GSSG, NADP+ /NADPH relative balances (elements involved in redox homeostasis) were analyzed. Moreover, to explore the effect of NMC on mitochondrial biogenesis, the expression levels of Mfn1, Mfn2, OPA1, Fis1, and Drp1 were investigated. Finally, the expression levels of Parkin/PARK and PINK (genes involved in mitochondrial quality control), as well as LC3-I/II (mitophagy marker), were analyzed. Observations showed that NMC, dose-dependently, altered GSH/GSSG, NADP+ /NADPH relative balances, suppressed SOD expression and diminished its biochemical level, and repressed Nrf1 and Nrf2 expression levels. Moreover, it could change the Mfn1, Mfn2, OPA1, Fis1, and Drp1 expression pattern and stimulate the Parkin/PARK and PINK as well as LC3-I/II expression levels, dose-dependently. In conclusion, chronic and high-dose NMC is able to suppress the redox capacity by down-regulating the Nrf1 and Nrf2 expression. Finally, at high-dose levels, it is able to trigger mitophagy signaling in the testicles.
Topics: Male; Rats; Animals; Rats, Wistar; Organelle Biogenesis; Curcumin; Glutathione Disulfide; Mitophagy; NADP; NF-E2-Related Factor 2; Testis; Hydrolases; Micelles; Oxidation-Reduction; Superoxide Dismutase
PubMed: 37660650
DOI: 10.1016/j.biopha.2023.115363 -
Journal of Controlled Release :... Jan 2023New and improved nanomaterials are constantly being developed for biomedical purposes. Nanomaterials based on elastin-like polypeptides (ELPs) have increasingly shown... (Review)
Review
New and improved nanomaterials are constantly being developed for biomedical purposes. Nanomaterials based on elastin-like polypeptides (ELPs) have increasingly shown potential over the past two decades. These polymers are artificial proteins of which the design is based on human tropoelastin. Due to this similarity, ELP-based nanomaterials are biodegradable and therefore well suited to drug delivery. The assembly of ELP molecules into nanoparticles spontaneously occurs at temperatures above a transition temperature (T). The ELP sequence influences both the T and the physicochemical properties of the assembled nanomaterial. Nanoparticles with desired properties can hence be designed by choosing the appropriate sequence. A promising class of ELP nanoparticles are micelles assembled from amphiphilic ELP diblock copolymers. Such micelles are generally uniform and well defined. Furthermore, site-specific attachment of cargo to the hydrophobic block results in micelles with the cargo shielded inside their core, while conjugation to the hydrophilic block causes the cargo to reside in the corona where it is available for interactions. Such control over particle design is one of the main contributing factors for the potential of ELP-based micelles as a drug delivery system. Additionally, the micelles are easily loaded with protein or peptide-based cargo by expressing it as a fusion protein. Small molecule drugs and other cargo types can be either covalently conjugated to ELP domains or physically entrapped inside the micelle core. This review aims to give an overview of ELP-based micelles and their applications in nanomedicine.
Topics: Humans; Micelles; Elastin; Nanomedicine; Peptides; Drug Delivery Systems
PubMed: 36526018
DOI: 10.1016/j.jconrel.2022.12.033