ChemComm
Communication
The temperature-dependent particle formation is ascribed crosslinking of Np building blocks is established with time, as
to the dynamic character of the supramolecular host–guest indicated by the time-dependent measurements. Stable particle
binding. After initial rapid ternary complex formation, disas- formation requires termination of the multivalent interactions
sembly and reassembly of the four building blocks is required that are established between Np8-PAMAM and MV-PEI in the
for well-defined particle formation. At elevated temperatures presence of CB[8]. The results obtained for the size dependence
the required rearrangement is enhanced which leads to faster show that more than 50% monovalent Np-PEG is required to
SNP formation. Such a time-dependent particle formation has stabilize the NPs. Distinct supramolecular NP size control is
not been reported so far for SNPs based on CD–Ad host–guest achieved by fine-tuning the balance of multivalent vs. mono-
interactions. In all cases reported, SNP formation was observed valent interactions. As expected, increasing the concentration of
directly after mixing the supramolecular components. We the multivalent dendrimer leads to the formation of larger SNPs.
attribute the difference in dynamics to the stronger and more
In conclusion, we have developed a novel, versatile strategy
slowly exchanging complexes of CB vs. CD. An important for the preparation of SNPs, in which CB[8] acts as an inter-
advantage of the use of supramolecular interactions for the molecular connector between MV-PEI, Np8-PAMAM and Np-PEG
formation of SNPs is their responsive character. The triggered upon formation of a ternary supramolecular CT-complex. Of
disassembly of the SNPs reported here has been induced by the particular importance are the observed assembly kinetics and
reductant Na2S2O4 (Fig. S8, ESI†). After addition of the reducing the size-focusing in time, which indicates progression towards
agent, initially observed NPs could not be detected anymore thermodynamic equilibrium. The distinct size tunability as well
using DLS and SEM. Reduction of the dicationic MV species as the stimulus-responsive particle disassembly make such NPs
leads to the formation of MV + radical cations which undergo a potential candidate for biomedical applications in drug delivery,
stable homo-ternary complex formation involving two MV peptide therapeutics as well as in vivo sensing.
radical cations in one CB[8] host.23 Thereby, a different supra-
molecular complex is formed, and the Np entities are released Sciences of the Netherlands Organization for Scientific
This work was supported by the Council for Chemical
from the CB[8] cavities and, consequently, the SNPs dissolve.
SNP size control was achieved by varying the ratio of mono-
valent Np-PEG to multivalent Np8-PAMAM, while keeping the
overall Np concentration constant and maintaining an equimo-
lar CB[8]–MV–Np stoichiometry. SNPs were observed for all
samples as shown by DLS (Fig. S9, ESI†) and SEM (Fig. S10(a)–
(e), ESI†) and the size of the observed SNPs strongly depends on
the origin of the Np derivative. In particular, by increasing the
amount of Np derived from Np8-PAMAM from 10% to 35%, an
increase in particle size from 57 Æ 11 nm to 115 Æ 13 nm and
from 51 Æ 13 nm to 137 Æ 16 nm was observed using SEM and
DLS, respectively. As seen in Fig. 4, the observed SNP size
exhibits an apparent linear relationship with the relative amount
of Np derived from Np8-PAMAM. For samples containing 50% or
more of Np derived from Np8-PAMAM, DLS showed dh beyond
1000 nm (Fig. S9, ESI†), as well as precipitation. The formation of
SNPs is established by multivalent interactions in the core
and monovalent interactions of Np-PEG at the outer surface of
the particles. Thereby an equilibrium between capping and
Research (NWO-CW; Vici grant 700.58.443 to J.H.).
Notes and references
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6742 Chem. Commun., 2013, 49, 6740--6742
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This journal is The Royal Society of Chemistry 2013