Charged Polypeptide Vesicles with Controllable Diameter

Contribution from the Materials Department, University of California at Santa Barbara, Santa Barbara, California 93106, USA.
Journal of the American Chemical Society (Impact Factor: 12.11). 10/2005; 127(35):12423-8. DOI: 10.1021/ja053557t
Source: PubMed


We report the preparation and characterization of charged, amphiphilic block copolypeptides that form stable vesicles and micelles in aqueous solution. Specifically, we prepared and studied the aqueous self-assembly of a series of poly(L-lysine)-b-poly(L-leucine) block copolypeptides, KxLy, where x ranged from 20 to 80 and y ranged from 10 to 30 residues, as well as the poly(L-glutamatic acid)-b-poly(L-leucine) block copolypeptide, E60L20. Furthermore, the vesicular assemblies show dynamic properties, indicating a high degree of membrane fluidity. This characteristic provides stimuli-responsive properties to the vesicles and allows fine adjustment of vesicle size using liposome-based extrusion techniques. Vesicle extrusion also provides a straightforward means to trap solutes, making the vesicles promising biomimetic encapsulants.

13 Reads
  • Source
    • "To date, polymersomes have been assembled from diverse di-and triblock copolymers [86]. Even bio-inspired building blocks such as various peptide residues and polysaccharides can be employed successfully to tune membrane formation [87] [88] [89] [90] [91] [92] [93] [94]. Zwitterionic-[95], sensor-responsive [96] [97] and stimuli-responsive building blocks have been used to prepare membranes with desired properties. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell.
    FEBS letters 06/2012; 586(15):2146-56. DOI:10.1016/j.febslet.2012.05.033 · 3.17 Impact Factor
  • Source
    • "The formation of purely polypeptide polymer vesicles was first demonstrated with the amphiphilic diblock co-polypeptide [poly(N ε -2-(2-(2-methoxyethoxy)ethoxy)acetyl-L- lysine] x -(poly-L-leucine) y (K x L y ) (Bellomo 2004) where the size and structure of these vesicles are dictated primarily by the ordered conformation of the peptide segments. Further work with K x L y has demonstrated the tunability of the aggregates where the fluidity of the vesicle membrane allows for control of vesicle size and the morphology of aggregates can be tuned with changes in the chain lengths of polylysine and polyleucine (Holowka 2005). By replacing the poly-lysine block of the K x L y co-polypeptide with poly-arginine (R x L y ), it is possible to impart the enhanced cellular delivery properties of other arginine-rich protein-transduction domains (i.e. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymersomes are polymer-based vesicular shells that form upon hydration of amphiphilic block copolymers. These high molecular weight amphiphiles impart physicochemical properties that allow polymersomes to stably encapsulate or integrate a broad range of active molecules. This robustness together with recently described mechanisms for controlled breakdown of degradable polymersomes as well as escape from endolysosomes suggests that polymersomes might be usefully viewed as having structure/property/function relationships somewhere between lipid vesicles and viral capsids. Here we summarize the assembly and development of controlled release polymersomes to encapsulate therapeutics ranging from small molecule anti-cancer drugs to siRNA and therapeutic proteins.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 11/2008; 71(3):463-74. DOI:10.1016/j.ejpb.2008.09.025 · 3.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly(ethylene oxide), poly(L-lysine), and poly(ɛ-caprolactone) arms, PEO(-b-PLL)-b-PCL, and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors, PEO(-b-PZLL)-b-PCL, were synthesized at first via the combination of consecutive “click” reactions and ring-opening polymerizations (ROP), where PZLL is poly(ɛ-benzyloxycarbonyl-L-lysine). Subsequently, the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers, PEO(-b-PLL)-b-PCL. In aqueous media at pH 7.4, PEO(-b-PLL)-b-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug, paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA (pDNA) at N/P ratios higher than ca. 2. Thus, PEO(-b-PLL)-b-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore, polyplexes of pDNA with paclitaxel-loaded PEO(-b-PLL)-b-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting, imaging, and diagnostics.
    Chinese Journal of Polymer Science 06/2013; 31(6). DOI:10.1007/s10118-013-1281-0 · 1.84 Impact Factor
Show more