Achieving precise control over the morphology and function of polymeric nanostructures during self-assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary-structure-directed self-assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide-inherent process of secondary-structure formation allows for the synthesis of spherical and worm-like core-cross-linked architectures from the same block copolymer, introducing a simple yet powerful approach to versatile peptide-based core-shell nanostructures.
Nanocarrier-based drug delivery is a promising therapeutic approach that offers unique possibilities for the treatment of various diseases. However, inside the blood stream, nanocarriers’ properties may change significantly due to interactions with proteins, aggregation, decomposition or premature loss of cargo. Thus, a method for precise, in situ characterization of drug nanocarriers in blood is needed. Here we show how the fluorescence correlation spectroscopy that is a well-established method for measuring the size, loading efficiency and stability of drug nanocarriers in aqueous solutions can be used to directly characterize drug nanocarriers in flowing blood. As the blood is not transparent for visible light and densely crowded with cells, we label the nanocarriers or their cargo with near-infrared fluorescent dyes and fit the experimental autocorrelation functions with an analytical model accounting for the presence of blood cells. The developed methodology contributes towards quantitative understanding of the in vivo behavior of nanocarrier-based therapeutics.
Präzise Kontrolle über Morphologie und Funktion polymerer Nanostrukturen im Rahmen der Selbstorganisation stellt nachwie vor eine Herausforderung im Feld der Materialund biomedizinischen Wissenschaften dar,insbesondere wenn unabhängige Kontrolle über einzelneP artikeleigenschaften erwünschti st. Hier wird über Sekundärstruktur-gesteuerte Selbstorganisation von Nanostrukturen basierend auf amphiphilen Blockcopolypept(o)iden berichtet und eine Strategie zur bio-reversiblen Einstellung der Kernpolaritätu nd -funktion unabhängig von der Partikelpräparation vorgestellt. Der Peptiden eigene Prozess der Sekundärstrukturbildung erlaubt so die Herstellung sphärischer und wurmartiger kernvernetzter Architekturen ausgehend von ein und demselben Blockcopolymer und bietet einen simplen, aber dennochleistungsfähigen Ansatz zur Herstellung vielseitiger peptidbasierter Nanopartikel.
ABC‐type triblock copolymers are a rising platform especially for oligonucleotide delivery as they offer an additional functionality besides the anyhow needed functions of shielding and complexation. The authors present a polypept(o)ide‐based triblock copolymer synthesized by amine‐initiated ring‐opening polymerization (ROP) of N‐carboxyanhydrides (NCAs), comprising a shielding block A of polysarcosine (pSar), a poly(S‐ethylsulfonyl‐l‐cystein) (pCys(SO2Et)) block B for bioreversible and chemo‐selective cross‐linking and a poly(l‐lysine) (pLys) block C for complexation to construct polyion complex (PIC) micelles as vehicle for small interfering RNA (siRNA) delivery. The self‐assembly behavior of ABC‐type triblocks is investigated to derive correlations between block lengths of the polymer and PIC micelle structure, showing an enormous effect of the β‐sheet forming pCys(SO2Et) block. Moreover, the block enables the introduction of disulfide cross‐links by reaction with multifunctional thiols to increase stability against dilution. The right content of the additional block leads to well‐defined cross‐linked 50–60 nm PIC micelles purified from production impurities and determinable siRNA loading. These PIC micelles can deliver functional siRNA into Neuro2A and KB cells evaluated by cellular uptake and specific gene knockdown assays.
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