Cytotoxicity of Dendrimers

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.

Applications and Limitations of Dendrimers in Biomedicine

“…Cytotoxicity was highlighted in cationic, amine dendrimers. Studies also showed a correlation between cytotoxicity and dendrimer generation [ 39 , 40 ]. For example, the cytotoxicity of poly(amidoamine) (PAMAM) and poly(propylene imine) (PPI) dendrimers is directly proportional to concentration and generation, due to the presence of primary amines terminal zones.…”

“…A multitude of studies were conducted on the cytotoxicities of different dendrimers [ 26 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Normal and cancer cell lines of animal and human origin were studied, among which were B14 (Chinese hamster fibroblasts), N2a (mouse neuroblastoma), CHO (Chinese hamster ovary, BRL-3A (rat liver derived cells), H4IIE (rat hepatoma), HepG2 (human liver hepatocellular carcinoma), Caco-2 (colon adenocarcinoma), B16F10 (murine melanoma cells), SW480 (primary adenocarcinoma of colon), U87MG (glioblastoma), hTERT/E6/E7 (human immortalized astrocytes), HaCaT (human epidermal keratinocytes), SK-Mel-28 (human melanoma), MDA-MB-231 (breast cancer), SKOV3 (human ovarian carcinoma), HepG2 (human liver hepatocellular carcinoma) and MCF7 (human breast adenocarcinoma) [ 40 , 250 ].…”

<p>PAMAM Dendrimer Nanomolecules Utilized as Drug Delivery Systems for Potential Treatment of Glioblastoma: A Systematic Review</p>

“…This is important as unmodified PAMAM dendrimers are known to be cytotoxic and increase in cytotoxicity with increased size and cationic character of their surface. 64 Similar to Qiu and colleagues (2018), Uram and colleagues (2017) found increased uptake of biotinconjugated dendrimers compared to non-conjugated Docetaxel U87MG…”

Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance

“…Therefore, an appropriate approach to revert this systemic toxicity would be the targeted delivery of l-BSO to cancer cells using a nanoparticles-mediated strategy. In this sense, dendrimers are an outstanding drug delivery platform, and many efforts have been made in the last few years to circumvent their cytotoxicity [21], encouraging the fast translation into clinic applications in a near future. In this study, we developed polyurea (PURE) dendrimers, which are a special case of non-toxic [22] and non-hemolytic dendrimers up to very high concentrations (circa 50 µM, unpublished data), and that have already been explored in different nanotherapeutic strategies [23][24][25][26].…”