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It is a difficult task to create a simple, universal, clear, unambiguous, logical, and generally applicable classification or even nomenclature of different sorts of dendrimers. In general, dendrimers contain a core, branches, and surface functional groups. Sometimes the core is missing (e.g., MAPs), or the branches are missing (RAFTs). The classification can stress either the shape of the core, branches, or surface groups (linear, cyclic) or the chemical nature of the core (fullerene, porphyrin, calixarene, cyclodextrin, RAFT, etc.) or branches (peptide, carbohydrate, PEG, PAMAM, etc.)

The terms of toxicity and biocompatibility of dendrimers are closely related. For biomedical applications, dendrimers should be devoid of toxicity and immunogenicity. The first concept—“toxicity”—is mainly applied by pharmacompanies for description of adverse effects to cells, organs, or patients. The second concept—“biocompatibility”—belongs to the field of biomedical materials as an extent of their compatibility with the studied system. One can say that biocompatibility and toxicity are inversely proportional, i.e., the more biocompatible the less toxic it is. Since 1986, biocompatibility is defined as the capability of a material to act with a proper host response in a specific application. Therefore, a biocompatibility of material can be described only if the precise context of material usage is known. Without knowledge of the exact usage of dendrimer, any chemistry cannot be defined as nontoxic or biocompatible. Clinical experience with dendrimers is still in its infancy; therefore, it is impossible to specify any chemistry insistingly biocompatible or toxic. Coating of nanomaterials with glycodendrimers results in formation of biocompatible nanoparticles such as solid lipid nanoparticles, CNTs, fullerene C60, lanthanide (Ln3 +)-doped nanoparticles, and CdSe quantum dots. These nanoparticles are not only biocompatible but also recognize specific lectins such as Con A, PNA, and PTA. The topic of dendrimer toxicity and biocompatibility will be discussed in detail with many representative examples.

Solubility is a key property influencing behavior of compounds in nature, science, biomedical applications, etc. Hydrophobicity and poor solubility of drugs and other bioactive compounds limit their possible applications in drug delivery and formulation development. Therefore approximately 40 % of newly developed drugs are rejected by the pharmaceutical industry and will never benefit a patient owing to poor bioavailability due to low water solubility and/or cell membrane permeability. In most cases, this problem can be solved by dendrimers. Many examples of dendrimers with different cores, branches, structures, hydrophilic surface groups, and hydrophobic pockets are described, including PEGylated dendrimers. The application of dendrimers as solubility enhancers for many drugs, such as anticancer drugs, antidepressants, antifungal drugs, antihemorrhagic drugs, antihistaminics, anti-inflammatory drugs, and antimicrobial drugs, is discussed. Solubility is in close relation with delivery, bioavailability, and/or cell membrane permeability; therefore see also these chapters.

Due to a strong anti-amyloidogenic activity, dendrimers are powerful agents with potential application for treatment of Alzheimer’s, Parkinson’s and prion diseases. Moreover, phosphorus containing dendrimer are used for sterilization of medical instruments in order to prevent transmission of prion diseases.

Dendrimers can be prepared by both convergent and divergent approaches. In the convergent approach, first suitable building blocks are prepared and then connected by lego chemistry, ligations or click chemistry. In the divergent approach, the synthesis is done stepwise. The advantage of convergent synthesis is greater difference between product and side products. The purification is therefore easier. On the other hand, the synthesis of big building blocks is complicated.

Dendrimers can serve also as antiparasitic tools. They can serve for vaccination, as well as, for specific delivery of toxic cargos. As examples, applications of dendrimers for treatment of various diseases caused by Schistosoma mansoni, Fasciola gigantica, Plasmodium falciparum, and Leishmania spp. are briefly mentioned.

The Possible biological applications of dendrimers stem from their capacity to influence the cell–cell interactions. These interactions are mediated by branched glycoconjugates forming a structure called glycocalyx present on the cell surface. Glycopeptide dendrimers, which can mimic these structures, thus can be used for detection of important players involved in carbohydrate-mediated cell–cell interactions or signaling. Moreover, they can be used as artificial modulators of glycoconjugate-mediated signaling and thus influence important processes, such as immune response, inflammation or fertilization. These types of glycodendrimers are also under investigation as antitumor or antimicrobial therapeutic agents.

Thanks to variable structures and properties, dendrimers are attractive for catalytic applications. They can act as catalytically active species, as well as, soluble supports onto which catalytically active species can be attached. Different sorts of dendrimer-encapsulated nanoparticles are used both in homogeneous and in heterogeneous catalysis. Examples of dendrimeric catalysts and their applications in many sorts of reactions, including chiral dendrimer catalysts and enantioselectivity in catalysis are given. Chiral dendrimer catalysts with a high level of molecular monodispersity, well-defined catalytic sites, and structural regularity, can be prepared either by attachment of achiral complexes to chiral dendrimer structures or by immobilization of chiral catalysts to achiral dendrimers.

Dendrimers, due to their unique chemical and biological properties, are considered to be highly suitable tools for regulation of immunity. They are endowed with unique capacity to expose artificial multivalent carbohydrate, glycoprotein or peptide antigens as highly defined three dimensional structures. A number of experimental vaccines has been developed against both infectious diseases and cancer. Notably, dendrimers can also be designed to be preferentially targeted to antigen-presenting cells and to activate them. As nucleic acid carriers, they can be utilized as carriers in DNA vaccines.

Before 1984, three classes of macromolecular architecture (i.e. linear, cross-linked, and branched) were widely accepted for construction of relatively polydisperse products of different molecular weights. Since that year, the “dendritic state” is acknowledged as a new, fourth class of polymer architecture. It can be divided to five subclasses: random hyperbranched polymers, dendrigrafts, dendrons, dendrimers, and tecto(dendrimers) or megamers. Due to the presence of a large number of terminal groups and the limitations or a complete lack of interpenetration, the physicochemical properties of dendrimers differ from those of classical polymers. On the other site, dendrimers and hyperbranched polymers are partly overlapping groups, which differ in regularity of structure, synthetic availability, and chemical variability. In comparison with hyperbranched polymers, dendrimers are more regular and better defined, but more difficult to prepare. The fundamental properties (both chemical and biological) of dendrimers are described. Dendritic chain reaction (DCR), a signal amplification technique that uses the disassembly properties of self-immolative dendrimers is also mentioned.

Delivery of nucleic acids to target cells can be achieved by both viral and nonviral delivery systems. Both of these methods have distinct advantages and disadvantages. In contrast to viral vectors, the nonviral ones provide the advantage of safety and flexibility. The disadvantage of nonviral carriers is their low efficiency. Inherent properties of dendritic nanoscale devices provide an ideal tool for development of synthetic (nonviral) carriers for delivery of nucleic acids. Among these properties, the defined architecture, high ratio of surface groups to molecular volume, and difference of hydropathic properties of interior and exterior are the most important for drug and gene delivery. Dendrimeric structures have been suggested to be used in gene therapy as potent carriers capable to, sometimes specifically, deliver DNA or RNA into the cells. Dendrimers are able to form complexes with many types of nucleic acids, such as plasmid DNA, antisense oligonucleotides, and RNA. Due to their defined architecture and a high ratio of multivalent surface moieties to molecular volume, they have become very important for the development of synthetic vectors for nucleic acid delivery. Indeed, dendrimer-based transfection agents have become routine tools for many molecular and cell biologists but the therapeutic delivery of nucleic acids complexed with dendrimer should be further investigated. The cationic dendrimers interact with the anionic backbone of nucleic acids mainly electrostatically. Complexed DNA is protected against degradation and the net positive charge of the dendrimer nucleic acid complex determines the transfection efficiency. However, highly cationic complexes are cytotoxic. Their properties can be tuned by many factors such as concentration of dendrimer amines and nucleic acid phosphates, salt concentration, stoichiometry, bulk solvent properties like pH, buffer strength, etc. For a development of dendriplex complexes with nucleic acids which can be used in gene therapy or, in general, as transfection reagents, knowledge of their transfection efficiencies and cytotoxicities is crucial.

Drugs are delivered by dendrimers by simple encapsulation, electrostatic interaction, or covalent conjugation. The application of dendrimer–drug conjugates by oral, intravenous, intraperitoneal, intratumoral, transdermal, ocular, etc. administration is discussed. Drug–dendrimer conjugates have two advantages over drug–dendrimer complexes and traditional drug dosing: prolonged lifetime and more stable level of the active substance. Many examples of different dendrimeric structures are given together with examples of their application in drug delivery. Dendrimers are also supposed to become an important tool for tissue-specific drug targeting. The topics of drug delivery, dendrimer solubility (both dendrimers as such and their influence to drug solubility), dendrimer toxicity and biocompatibility, are closely related and influence each other, therefore see also Chaps. 10 and 11.

Carbohydrates are expressed on majority of mammalian cell surfaces. They are bound to glycoproteins, proteins, and glycolipids, or to different cellular constituents, e.g. proteoglycans that are part of the cell membrane in clustered and multiantennary structures. These oligosaccharides represent signal transductors between extra- and intracellular media. Glyco- and glycopeptide dendrimers are excellent tools, which can be used for studies of inter- and intracellular signaling and also for their modulation. The capability of dendrimers to modulate intracellular signaling is strongly associated with their biological and therapeutic applications. In this chapter, several examples, how dendrimeric structures can influence intracellular enzymes (e.g. kinases or GTPases) that represent crucial components of intracellular signaling are presented.

A potential to serve as nanocarriers for various probes that can be conjugated on their external parts producing unique and defined three dimensional structures justifies dendrimers as candidates to be used as sensors or imaging tools. Typical examples, documenting their utilization as biosensors, are glycopolymers designed to bind specific lectins and endowed with intrinsic fluorescence. Dendrimers are used also for quantitative detection of different compounds, e.g. glucose, avidin, cDNA, dopamine, penicillamine, IgG, BSA, thrombin and many others. Other possibilities are conjugates with enzymes providing electrochemical signaling. Dendrimers are also under intensive studies as probes for magnetic resonance imaging.