Dendrimers in medical nanotechnology

Abstract

Dendrimers are a class of synthetically produced highly branched, spherical nanostructures that can be used as carrier molecules for imaging agents. A variety of dendrimers exist and each has biological properties that will alter its biodistribution. Dendrimers are composed of combinations of core types such as ethylene diamine (EDA), diaminobutyl (DAB), polyamidoamine (PAMAM) and polypropylimine (PPI) and different surface residues such as amine, carboxyl, and alcoholic groups. Increasing the number of primary amine groups attached to the core will increase the size of the dendrimer, which is known by the term ‘generation’ of the dendrimer. Because dendrimers are highly structured in size and shape and have a low poly-dispersity index, each dendrimer generation has distinct pharmacokinetic and pharmacodynamic properties which may prove advantageous for particular medical applications. Research has centered on developing these macromolecules as imaging agents for numerous modalities including magnetic resonance imaging, X-ray computed tomography, optical imaging and nuclear medicine. Another prospective function of dendrimers is as drug delivery vectors, whereby therapeutic payloads are encapsulated within the shell, or incorporated onto their multivalent surface, and targeted to tumor cells using ligands that specifically bind to cancer cells or in normal cells altered by nearby cancer cells. Furthermore, the larger size of high generation dendrimers offers potential to develop dual purpose agents that can act both as imaging agents and as delivery vectors, or can be imaged with more than one modality. Herein, we discuss the current and future applications of dendrimers in medicine and the central role they play in the emerging field of nanotechnology.

Figure 1

A schema of EDA core PAMAM dendrimer-based MRI contrast agent is shown.

Figure 2

Contrast enhanced whole body 3D-MRIs of a normal mouse using EDA core PAMAM-G4 dendrimer-based MRI contrast agent (left) and DAB core PPI-G5 dendrimer-based MRI contrast agent (right) are shown. Despite of similar physical sizes, a little less hydrophilic DAB core PPI-G5 based agent auumulated in the liver significantly more than EDA core PAMAM-G4.

Figure 3

5-color NIR fluorescence and radionuclide lymphatic drainage imaging of the head and neck region obtained with dendrimer-based dual modality contrast agents are shown. Five different lymphatic drainages are separately shown in 5-color NIR fluorescence imaging (left) and quantitatively shown in a schintigram (right).

Figure 4

A scintigram, which depicted the delivery of anti-sense oligo-nucleotide with (left) or without (right) dendrimer as a delivery vehicle, is shown. Arrows indicate tumors and arrowheads indicate kidneys.