Impact of Branching on the Solution Behavior and Serum Stability of Starlike Block Copolymers

Abstract

The size control of nanomedicines for tumor diagnosis and therapy is of high importance, since it enables or disables deep and sufficient tumor penetration. Amphiphilic star-shaped block copolypept­(o)­ides offer substantial promise to precisely adjust the hydrophobic core and the hydrophilic corona, independent of each other, and therefore simultaneously control the size dimension in the interesting size range from 10 to 30 nm. To gain access to core–shell structures of such sizes, 3-arm and 6-arm PeptoStars, based on poly­(γ-tert-butyloxycarbonyl-l-glutamate)-b-polysarcosine (pGlu­(OtBu)-b-pSar), were prepared via controlled living ring-opening polymerization (ROP) of the corresponding N-carboxyanhydrides. Moreover, size exclusion chromatography (SEC) proves the presence of well-defined star shaped polymers with molecular weights from 38 to 88 kg/mol with low polymer dispersities of 1.16 to 1.23. By varying the α-helical peptide core and maintain a constant polysarcosine corona, hydrodynamic size analyses revealed the importance of using a sufficiently large and dense hydrophilic shielding corona to prevent aggregation of the hydrophobic core and obtain uniform-sized spherical-shaped particles with hydrodynamic diameters below 24 nm. Fluorescence correlation spectroscopy (FCS) additionally demonstrates the absence of protein adsorption in human plasma for 6-arm polypept­(o)­ide stars and thus confirms polysarcosine as stealthlike material.

Multifunctional Cationic PeptoStars as siRNA Carrier: Influence of Architecture and Histidine Modification on Knockdown Potential

“…In line with the findings of Huesmann et al, the polypeptide cores with degree of poly merization of 10 and 25 for each arm displayed broader SEC elugrams, which can be attributed to the coexistence of peptides in random coil and helical conformation differing substantially in hydrodynamic volume. [43,44] As indicated in Figure 1, a clear shift to lower elution volumes along with a distinct increase in molecular weights is obtained in all cases. Once again, the polypept(o)ide formation proceeded independently of the applied cystamine-or butylbased initiator and lead to desired chain length as determined by 1 H NMR.…”

“…[45] The characterizations of the 3-arm and 6-arm polypept(o)ide star-like polymers by single angle DLS was performed in methanol, since 3-arm systems aggregated in aqueous solution. [43] The 3-arm polypept(o)ide stars reveal hydrodynamic diameters (D h ) from around 7 to 12 nm (see Figure 2A), whereas for 6-arm polypept(o)ides, D h from 8 to 14 nm were detected. As expected, the small 6-arm polypept(o)ide stars ((pLys(Boc) 10 -pSar 100 ) 6 ) show slightly decreased sizes in comparison to the 3-arm polypept(o)ides of equal overall chain length (see Table 1).…”

“…The detailed syntheses of all initiators were described previously. [43] One class of initiators contains disulfide bonds between the core and the individual arms, which provide biodegradability in the intracellular reductive environment and consequently, the disassembly of the poly meric arms can induce the release of siRNA in the cytosol. The complete synthetic pathway for polypept(o)ide based star-like polymers is shown in Scheme 1.…”

The generation of stabilized supramolecular nanorods from star-shaped polyglutamates

“…While vast numbers of studies of different BTA-based molecules (including polypept(o)ids) have been carried out, the majority of the molecules able to self-assemble were uncharged. 18 Some studies attempted to combine BTA-cores with poly-amino acid derivatives; however, BTA played the role of a multifunctional core rather than supramolecular motif in all cases. [18][19][20] Besenius pioneered a method of charge screening for small BTA-based molecules bearing ionizable groups with low molecular weight salts, achieving control for up to nine charges for Newkome dendron-decorated molecules.…”

“…18 Some studies attempted to combine BTA-cores with poly-amino acid derivatives; however, BTA played the role of a multifunctional core rather than supramolecular motif in all cases. [18][19][20] Besenius pioneered a method of charge screening for small BTA-based molecules bearing ionizable groups with low molecular weight salts, achieving control for up to nine charges for Newkome dendron-decorated molecules. 21 We hypothesized that replacing Newkome dendrons with small PGA chains should allow the formation of stable structures that can self-assemble in water and other physiological solutions.…”