Abstract
Drug delivery systems are molecular platforms in which an active compound is packed into or loaded on a biocompatible nanoparticle. Such a solution improves the activity of the applied drug or decreases its side effects. Dendrimers are promising molecular platforms for drug delivery due to their unique properties. These macromolecules are known for their defined size, shape, and molecular weight, as well as their monodispersity, the presence of the void space, tailorable structure, internalization by cells, selectivity toward cells and intracellular components, protection of guest molecules, and controllable release of the cargo. Dendrimers were tested as carriers of various molecules and, simultaneously, their toxicity was examined using different cell lines. It was discovered that, in general, dendrimer cytotoxicity depended on the generation, the number of surface groups, and the nature of terminal moieties (anionic, neutral, or cationic). Higher cytotoxicity occurred for higher-generation dendrimers and for dendrimers with positive charges on the surface. In order to decrease the cytotoxicity of dendrimers, scientists started to introduce different chemical modifications on the periphery of the nanomolecule. Dendrimers grafted with polyethylene glycol (PEG), acetyl groups, carbohydrates, and other moieties did not affect cell viability, or did so only slightly, while still maintaining other advantageous properties. Dendrimers clearly have great potential for wide utilization as drug and gene carriers. Moreover, some dendrimers have biological properties per se, being anti-fungal, anti-bacterial, or toxic to cancer cells without affecting normal cells. Therefore, intrinsic cytotoxicity is a comprehensive problem and should be considered individually depending on the potential destination of the nanoparticle.
Highlights
Dendrimers, known as starburst polymers [1], cascade molecules, or arborols [2], were developed in 1980s
After a 48-h treatment, both cell lines presented 100% dendrimer internalization efficiency for the tested concentrations. These results suggest that CMCht/Poly(amido amine) (PAMAM) nanoparticles may be an attractive drug delivery system for brain tumor treatment [61]
The results suggest that cationic phosphorus dendrimers (CPDs) G3 and generation 4 (G4) were cytotoxic and genotoxic for chosen human cells [77]
Summary
Dendrimers, known as starburst polymers [1], cascade molecules, or arborols [2], were developed in 1980s. Dendrimers are characterized by a compact structure and a strictly predictable molecular weight (MW) They are monodisperse, polyvalent, usually globular macromolecules with a regular and highly branched three-dimensional architecture. Thanks to their specific structure and the presence of controllable internal cavities, these nanomolecules are perfect for the encapsulation of guest drugs (Figure 3A). As compounds that are so intensively studied for their potential use in biomedicine, dendrimers should meet several criteria. They should be non-toxic, non-immunogenic, biopermeable (possess the ability to cross biobarriers), able to stay in blood circulation until the desired effects occur, and able to target specific biological structures. We discuss whether the toxicity of dendrimers limits their biomedical applications, and what the main strategies to improve their biocompatibility are
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