Recently, supramolecular amphiphilic assembly constructed from molecularinduced aggregation gained a lot of attention due to their functional versatility,
biocompatibility, and being tunably responsive to various external stimuli [4, 5 ].
Randaccio, Purrello, and Sciotto came up with the early prototype of “molecularinduced aggregation”. They found that the complexation between a tetrakis-acetatesmodified sulfonatocalixarenes and a cationic porphyrin led to the formation of
aggregates with pH-tunable host/guest stoichiometries [6]. After that, other watersoluble macrocyclic molecules, including cucurbiturils [7, 8], pillararenes [9–12],
and cyclodextrins [13, 14], were also employed to construct supramolecular amphiphiles through the “molecular-induced aggregation” strategy. In a molecular-induced
aggregation process, the host molecules were able to promote the self-aggregation of
aromatic or amphiphilic guest molecules by lowering the critical aggregation concentration (CAC), increasing the stability and compactness, and regulating the
degree of order in the aggregates. Three key factors are required for the “molecular-induced aggregation”: (1) strong binding affinities between hosts and the polar
head groups of guests, (2) charge compensation between hosts and guests, and (3)
the pre-organized cyclic scaffold of hosts. For the amphiphilic guest molecules, the
electrostatic repulsion between the polar head groups prevents the formation of large
three-dimensional assemblies. Upon complexation with hosts, the electrostatic
repulsion between the polar head groups is replaced by the electrostatic attraction
between host and guest which facilitates the formation of large assemblies. The
“molecular-induced aggregation” process can be summarized as two steps. First, the
host and guest molecules rapidly form a complex driven by the host-guest interactions. Then, the additional guest molecules readily integrate into the complex, which
further transform into a 2:n complexes and large three-dimensional aggregates.
Compared with other macrocyclic host compounds, multi-charged cyclodextrins are a series of novel “molecular-induced aggregation” candidates. The
cavities of cyclodextrin can include various inorganic/organic/biological molecules and ions with high size/shape selectivity [15, 16]. The negative charge
density of sulfatocyclodextrin (SCD) is much higher which is also the most
important “molecular-induced aggregation” factor. This chapter mainly summarizes the recent researches on the supramolecular assembly constructed from
multi-charged cyclodextrin-induced aggregation and their applications in biological and medical fields.
21.2 Supramolecular Assembly Constructed from Polyanionic
Cyclodextrin-Induced Aggregation
A typical example of polyanionic cyclodextrin-induced aggregation was a trypsinresponsive supramolecular assembly constructed of SCD and protamine (Fig. 1)
[17]. Protamine, a natural protein, was used as an excipient in insulin formulations
with potential biological applications including binding DNA and providing a highly
compact conjuration of chromatin in the nucleus of the sperm [18]. As a natural
cationic protein, protamine has no amphiphilic self-assembly property for its high
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P.-Y. Li et al.
biocompatibility, and being tunably responsive to various external stimuli [4, 5 ].
Randaccio, Purrello, and Sciotto came up with the early prototype of “molecularinduced aggregation”. They found that the complexation between a tetrakis-acetatesmodified sulfonatocalixarenes and a cationic porphyrin led to the formation of
aggregates with pH-tunable host/guest stoichiometries [6]. After that, other watersoluble macrocyclic molecules, including cucurbiturils [7, 8], pillararenes [9–12],
and cyclodextrins [13, 14], were also employed to construct supramolecular amphiphiles through the “molecular-induced aggregation” strategy. In a molecular-induced
aggregation process, the host molecules were able to promote the self-aggregation of
aromatic or amphiphilic guest molecules by lowering the critical aggregation concentration (CAC), increasing the stability and compactness, and regulating the
degree of order in the aggregates. Three key factors are required for the “molecular-induced aggregation”: (1) strong binding affinities between hosts and the polar
head groups of guests, (2) charge compensation between hosts and guests, and (3)
the pre-organized cyclic scaffold of hosts. For the amphiphilic guest molecules, the
electrostatic repulsion between the polar head groups prevents the formation of large
three-dimensional assemblies. Upon complexation with hosts, the electrostatic
repulsion between the polar head groups is replaced by the electrostatic attraction
between host and guest which facilitates the formation of large assemblies. The
“molecular-induced aggregation” process can be summarized as two steps. First, the
host and guest molecules rapidly form a complex driven by the host-guest interactions. Then, the additional guest molecules readily integrate into the complex, which
further transform into a 2:n complexes and large three-dimensional aggregates.
Compared with other macrocyclic host compounds, multi-charged cyclodextrins are a series of novel “molecular-induced aggregation” candidates. The
cavities of cyclodextrin can include various inorganic/organic/biological molecules and ions with high size/shape selectivity [15, 16]. The negative charge
density of sulfatocyclodextrin (SCD) is much higher which is also the most
important “molecular-induced aggregation” factor. This chapter mainly summarizes the recent researches on the supramolecular assembly constructed from
multi-charged cyclodextrin-induced aggregation and their applications in biological and medical fields.
21.2 Supramolecular Assembly Constructed from Polyanionic
Cyclodextrin-Induced Aggregation
A typical example of polyanionic cyclodextrin-induced aggregation was a trypsinresponsive supramolecular assembly constructed of SCD and protamine (Fig. 1)
[17]. Protamine, a natural protein, was used as an excipient in insulin formulations
with potential biological applications including binding DNA and providing a highly
compact conjuration of chromatin in the nucleus of the sperm [18]. As a natural
cationic protein, protamine has no amphiphilic self-assembly property for its high
574
P.-Y. Li et al.