Encapulsation, transport, and selective release of active compounds on the molecular level are very important for administering cytotoxic or unstable active compounds, e.g., antitumor medication, DNA, or siRNA. For encapsulation and transport of active compounds it is crucial that the enclosed compounds are completely and initially irreversibly taken up by the molecular transporter. Release, however, should only occur under certain external stimili, e.g., in the acidic environment of tumor tissue. Perfect dendrimers like glycerine dendrimers have a defined core-shell structure with a clear separation between the inner branching dense scaffold and the functional end groups in the periphery. A dense shell used to be attached to dendrimers for permanent encapsulation and for transporting dyes and active substances. The disadvantage of these perfect dendrimers for most applications is their multi-step and therefore tedious synthesis. Hyperbranched polymers like poly(ethylene imine) and polyglycerol are commercially available in large quantities. Through chemical differentiation and selective functionalization of the terminal groups it is possible to convert the less perfect, dendritic polymers into core-shell architectures. These systems are suitable for transport and release of active substances like dyes and drugs (Scheme 1).
Functionally cleavable nanocapsules based on dendritic polymers (polyglycerol or polyethylene imine). Gray: dendritic core, blue: cleavable shell.
The core-shell architectures are relatively stable under physiological conditions (neutral environment) and only cleave upon certain external stimili, e.g., acidic environment, in which case the active substance is released. It could be shown for dendritic polyethylenimines that in addition to the antitumor active substances like mercaptorpurine, MTX, and even short DNA fragments (oligonucleotides) as well as bacteriostatic silver nanoparticles could be absorbed. In further research projects these cleavable nanocapsules are used to transport and selectively release active substances such as cytostatic drugs in, for example, 'acidic' tumor tissue. The deciding advantage of molecular nanocarriers compared to covalent polymer active substance conjugates is their easy manufacturing and great flexibility. Stable molecular nanocarriers have also been easily produced based on dendritic polyethylene imines or polyglycerol (Figure 1).
These nanotransporters are now being examined for various applications including the transport of catalysts and active metal nanoparticles. Furthermore, our group in collaboration with the Zimmerman group has recently developed crosslinked dendritic nanocarrier systems which were designed for high transport efficiency and selectivity, respectively.
Dendritic multishell architectures and cross-linked nanocarrier.
In an attempt to achieve a controlled release of the guest molecules, photoresponsive cross-linked systems were prepared by the introduction of o-nitrobenzyl groups within the shell. The photodegradable nanocapsules retained the capacity and selectivity for encapsulating bioactive molecules, while modification of the building blocks allowed substantial control over host–guest stability. The light-triggered release of rose bengal from the dye complex in chloroform was confirmed by irradiation of the solution at 350 nm monochromatic light (Figure 2). The versatility of the system was proven by hydroxylation of the shell which yielded fully water-soluble cross-linked analogues. These tend to form aggregates of about 100 nm diameter with a narrow size distribution in pure water which break down at higher ionic strength. A weak interaction of these systems was found with different water insoluble species, e.g., nimodipine, pyrene, and Nile red.