Outer membrane vesicles (OMVs) are nanoscale spherical vesicles released from Gram‐negative bacteria. The lipid bilayer membrane structure of OMVs consists of similar components as bacterial membrane ...and thus has attracted more and more attention in exploiting OMVs' bio‐applications. Although the endotoxic lipopolysaccharide on natural OMVs may impose potential limits on their clinical applications, genetic modification can reduce their endotoxicity and decorate OMVs with multiple functional proteins. These genetically engineered OMVs have been employed in various fields including vaccination, drug delivery, cancer therapy, bioimaging, biosensing, and enzyme carrier. This review will first briefly introduce the background of OMVs followed by recent advances in functionalization and various applications of engineered OMVs with an emphasis on the working principles and their performance, and then discuss about the future trends of OMVs in biomedical applications.
Bio‐applications of OMVs
The structural parameters of fluid phase bilayers composed of phosphatidylcholines with fully saturated, mixed, and branched fatty acid chains, at several temperatures, have been determined by ...simultaneously analyzing small-angle neutron and X-ray scattering data. Bilayer parameters, such as area per lipid and overall bilayer thickness have been obtained in conjunction with intrabilayer structural parameters (e.g. hydrocarbon region thickness). The results have allowed us to assess the effect of temperature and hydrocarbon chain composition on bilayer structure. For example, we found that for all lipids there is, not surprisingly, an increase in fatty acid chain trans–gauche isomerization with increasing temperature. Moreover, this increase in trans–gauche isomerization scales with fatty acid chain length in mixed chain lipids. However, in the case of lipids with saturated fatty acid chains, trans–gauche isomerization is increasingly tempered by attractive chain–chain van der Waals interactions with increasing chain length. Finally, our results confirm a strong dependence of lipid chain dynamics as a function of double bond position along fatty acid chains.
► Fluid bilayers composed of phosphatidylcholines are studied at several temperatures. ► Structural parameters are determined by neutron and X-ray scattering analysis. ► Thermal behavior of bilayer interactions is dominated by trans–gauche isomerization. ► Van der Waals interactions dictate chain length dependence in saturated lipids. ► Lipid chain dynamics depend strongly on double bond position.
Combinatory modulation of the physical and biochemical characteristics of nanocarrier delivery systems is an emergent topic in the field of nanomedicine. Here, we studied the combined effects of ...incorporation of active targeting moieties into nanocarriers and their morphology affecting the enhanced permeation and retention effect for nanomedicine cancer therapy. Self-assembled lipid discoidal and vesicular nanoparticles with low-polydispersity sub-50 nm size range and identical chemical compositions were synthesized, characterized, and correlated with in vitro cancer cellular internalization, in vivo tumor accumulation and cancer treatments. The fact that folate-associated bicelle yields the best outcome is indicative of the preference for discoidal carriers over spherical carriers and the improved targeting efficacy due to the targeting ligand/receptor binding. The approach is successfully adopted to design the nanocarriers for photodynamic therapy, which yields a consistent trend in in vitro and in vivo efficacy: folate nanodiscs > folate vesicles > nonfolate nanodiscs > nonfolate vesicles. Folate discs not only have shown a higher tumor uptake and photothermal therapeutic efficiency, but also minimize skin photosensitivity side effects. The advantages of nanodiscoidal bicelles as nanocarriers, including well-defined size, robust formation, easy encapsulation of hydrophobic molecules (therapeutics and/or diagnostics), easy incorporation of targeting molecules, and low toxicity, enable the scalable manufacturing of a generalized in vivo multimodal delivery platform.
Bicellar systems have become popularized as their rich morphology can be applied in biochemistry, physical chemistry, and drug delivery technology. To the biochemical field, bicelles are powerful ...model membranes for the study of transmembrane protein behavior, membrane transport, and environmental interactions with the cell. Their morphological responses to environmental changes reveal a profound fundamental understanding of physical chemistry related to the principle of self-assembly. Recently, they have also drawn significant attention as theranostic nanocarriers in biopharmaceutical and diagnostic research due to their superior cellular uptake compared to liposomes. It is evident that applications are becoming broader, demanding to understand how the bicelle will form and behave in various environments. To consolidate current works on the bicelle's modern applications, this review will discuss various effects of composition and environmental conditions on the morphology, phase behavior, and stability. Furthermore, various applications such as payload entrapment and polymerization templating are presented to demonstrate their versatility and chemical nature.
Display omitted
•The important parameters of controlling the formation of discoidal bicelles are presented.•The structural stability and lipid transfer of discoidal bicelles are discussed.•The applications of bicelles are summarized.
Targeting Breast Cancer Metastasis Jin, Xin; Mu, Ping
Breast Cancer: Basic and Clinical Research,
01/2015, Letnik:
2015, Številka:
S1
Journal Article, Book Review
Recenzirano
Odprti dostop
Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from ...distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting.
The authors designed a structurally stable nano‐in‐nano (NANO2) system highly capable of bioimaging via an aggregation‐enhanced NIR excited emission and photoacoustic response achieved based on ...atomically precise gold nanoclusters protected by linear thiolated ligands Au25(SCnH2n+1)18, n = 4–16 encapsulated in discoidal phospholipid bicelles through a one‐pot synthesis. The detailed morphological characterization of NANO2 is conducted using cryogenic transmission electron microscopy, small/wide angle X‐ray scattering with the support of molecular dynamics simulations, providing information on the location of Au nanoclusters in NANO2. The photoluminescence observed for NANO2 is 20–60 times more intense than that of the free Au nanoclusters, with both excitation and emission wavelengths in the near‐infrared range, and the photoacoustic signal is more than tripled. The authors attribute this newly discovered aggregation‐enhanced photoluminescence and photoacoustic signals to the restriction of intramolecular motion of the clusters’ ligands. With the advantages of biocompatibility and high cellular uptake, NANO2 is potentially applicable for both in vitro and in vivo imaging, as the authors demonstrate with NIR excited emission from in vitro A549 human lung and the KB human cervical cancer cells.
The rational design of NANO2 as an imaging/theranostic platform is presented.
Peptide nucleic acids (PNAs) are nucleic acid analogs with hybridization properties and enzymatic stability superior to that of DNA. In addition to gene targeting applications, PNAs have garnered ...significant attention as bio‐polymers due to the Watson–Crick‐based molecular recognition and flexibility of synthesis. Here, PNA amphiphiles are engineered using chemically modified gamma PNA (8 mer in length) containing hydrophilic diethylene glycol units at the gamma position and covalently conjugated lauric acid (C12) as a hydrophobic moiety. Gamma PNA (γ PNA) amphiphiles self‐assemble into spherical vesicles. Further, nano‐assemblies (NA) are formulated using the amphiphilic γ PNA as a polymer via ethanol injection‐based protocols. Comprehensive head‐on comparison of the physicochemical and cellular uptake properties of PNA derived self‐ and NA is performed. Small‐angle neutron and X‐ray scattering analysis reveal ellipsoidal morphology of γ PNA NA that results in superior cellular delivery compate to the spherical self‐assembly. Next, the functional activities of γ PNA self‐and NA in lymphoma cells via multiple endpoints, including gene expression, cell viability, and apoptosis‐based assays are compared. Overall, it is established that γ PNA amphiphile is a functionally active bio‐polymer to formulate NA for a wide range of biomedical applications.
Herein, gamma peptide nucleic acids (γ PNA)‐based amphiphiles are engineered by conjugating hydrophobic lauric acid domain with γ PNA containing hydrophilic diethylene glycol scaffolds. γ PNA self‐assembles into large spherical vesicles with >200 nm diameter. In parallel comparison, it is investigated that γ PNA nano‐assemblies, formulated via ethanol injection, form small ellipsoidal vesicles (100 nm) with superior transfection features than γ PNA self‐assemblies.
The size, shape, stiffness (composition) and surface properties of nanoparticles (NPs) have been recognized as key design parameters for NP-mediated drug delivery platforms. Among them, the surface ...functionalization of NPs is of great significance for targeted drug delivery. For instance, targeting moieties are covalently coated on the surface of NPs to improve their selectively and affinity to cancer cells. However, due to a broad range of possible choices of surface decorating molecules, it is difficult to choose the proper one for targeted functions. In this work, we will review several representative experimental and computational studies in selecting the proper surface functional groups. Experimental studies reveal that: (1) the NPs with surface decorated amphiphilic polymers can enter the cell interior through penetrating pathway; (2) the NPs with tunable stiffness and identical surface chemistry can be selectively accepted by the diseased cells according to their stiffness; and (3) the NPs grafted with pH-responsive polymers can be accepted or rejected by the cells due to the local pH environment. In addition, we show that computer simulations could be useful to understand the detailed physical mechanisms behind these phenomena and guide the design of next-generation NP-based drug carriers with high selectivity, affinity, and low toxicity. For example, the detailed free energy analysis and molecular dynamics simulation reveals that amphiphilic polymer-decorated NPs can penetrate into the cell membrane through the "snorkeling" mechanism, by maximizing the interaction energy between the hydrophobic ligands and lipid tails. We anticipate that this work will inspire future studies in the design of environment-responsive NPs for targeted drug delivery.
Nature provides us a panorama of fibrils with tremendous structural polymorphism from molecular building blocks to hierarchical association behaviors. Despite recent achievements in creating ...artificial systems with individual building blocks through self-assembly, molecularly encoding the relationship from model building blocks to fibril association, resulting in controlled macroscopic properties, has remained an elusive goal. In this paper, by employing a designed set of glycopeptide building blocks and combining experimental and computational tools, we report a library of controlled fibril polymorphism with elucidation from molecular packing to fibril association and the related macroscopic properties. The growth of the fibril either axially or radially with right- or left-handed twisting is determined by the subtle trade-off of oligosaccharide and oligopeptide components. Meanwhile, visible evidence for the association process of double-strand fibrils has been experimentally and theoretically proposed. Finally the fibril polymorphs demonstrated significant different macroscopic properties on hydrogel formation and cellular migration control.
Display omitted
Solid lipid nanoparticles (SLNs) have gained tremendous attraction as carriers for controlled drug delivery. Despite numerous advances in the field, one long-standing historical ...challenge for their practical applications remains unmet: redispersibility after drying. In this work, a novel design of SLNs using a layer-by-layer (LbL) technique was developed and the formulations were optimized by surface response methodology (Box-Behnken design). To the best of our knowledge, this is the first study reporting the fabrication of SLNs from all natural ingredients in the absence of any synthetic surfactants or coatings. The SLNs were prepared by a combined solvent-diffusion and hot homogenization method, with soy lecithin as natural emulsifier (first layer), followed by the subsequent coating with sodium caseinate (second layer) and pectin (third layer), both of which are natural food biopolymers. The adsorption of pectin coating onto caseinate was reinforced by hydrophobic and electrostatic interactions induced by a pH-driven process along with thermal treatment. The innovative nano spray drying technology was further explored to obtain ultra-fine powders of SLNs. Compared to uncoated or single-layer coated SLNs powders, which showed severe aggregation after spray drying, the well-separated particles with spherical shape and smooth surface were obtained for layer-by-layer (LbL) SLNs, which were redispersible into water without variation of dimension, shape and morphology. The SLNs were characterized by Fourier transform infrared and high-performance differential scanning calorimetry for their physical properties. The LbL-coated SLNs based on all natural ingredients have promising features for future applications as drug delivery systems, overcoming the major obstacles in conventional spray drying and redispersing SLNs-based formulations.
PDF
