Dendrimers, an Emerging Opportunity in Personalized Medicine?

Abstract

Dendrimers are highly branched macromolecules tailorable at will to fulfil precise requirements. They have generated a great many expectations and a huge number of publications and patents in relation to medicine, including in relation to personalized medicine, but have resulted in very poor clinical translation up to now. As clinical trials are the first steps in view of developing new compounds for (a personalized) medicine, this review focusses on the clinical trials carried out with dendrimers. Many of these clinical trials have been recently posted (2020–2022); thus, only very few concern phase 3. The safety and efficiency of essentially two main types of dendrimers, based on polylysine and polyamidoamide scaffolds, have been assessed up to now. These dendrimers were tested with the aim of treating mainly bacterial vaginosis, cancers, and COVID-19.

Natural biomolecules and derivatives as anticancer immunomodulatory agents

“…Dendrimer-conjugated triptolide repolarized TAMs to a tumorsuppressive phenotype, decreased glioblastoma burden, while simultaneously limiting triptolide-associated cardiac and hepatic toxicity ( 195 ). Safety and efficacy of various dendrimers is currently being evaluated for a number of diseases with optimistic results ( 196 ) suggesting that dendrimer-triptolide conjugates may enter clinical testing soon. A nanocarrier system carrying triptolide and the active metabolite of irinotecan, SN38 inhibited NF-κB in both gastric cancer cells and cancer-associated fibroblasts (CAF) to inhibit CAF-induced cancer cell proliferation, migration and SN38-resistance, resulting in significant reduction in tumor burden in vivo ( 197 ).…”

Potential of nanoformulations in malaria treatment

“…Or diagnostic kits component as 3DNA ® from Gemisphere, or transfection agents such as Polyfect ® and Superfect ® from Qiagen ( Dias et al, 2020 ). In addition, according to information from the American repository ClinicalTrial.gov , some clinical trials evaluate drugs associated with dendrimers for treating cancer, bacterial infection, or COVID-19 ( Caminade, 2022 ). However, up to date, there are no dendrimer-based medicines to treat malaria, either under clinical evaluation or commercialization.…”

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells

“…2 Numerous therapeutic agents were tested over the years, but none of them succeeded in abolishing inflammation. 3 Unfortunately, we do not have non-empirical predictors for the rational design of drug combinations, which would achieve such a goal. 2 Among the many targets in inflammation are enzymes which regulate cytokine production, metalloproteinases which degrade the extracellular matrix, and the high mobility group box 1 (HMGB1) alarmin.…”

“…If not resolved, inflammation leads to aggravated neuropathologies caused by or associated with other factors . Numerous therapeutic agents were tested over the years, but none of them succeeded in abolishing inflammation . Unfortunately, we do not have non-empirical predictors for the rational design of drug combinations, which would achieve such a goal .…”

“…It is well established that HMGB1 binds heparan sulfate . In a recent review, we showed that multivalent non-covalent interactions can lead to strong polymer adhesion to biomolecules and other surfaces with positively charged surfaces. − Dendritic and linear polymers with suitable physicochemical properties could thus modulate biomacromolecule function and cell signaling. ,− Polyglycerols (PGs), water-soluble polyether polyols, are employed for biomedical applications owing to their hydrophilic nature and ability to be modified with specific reactive functional groups. , Polysulfates are therapeutic biomaterials which have anti-inflammatory properties. , Dendritic polyglycerol sulfate (dPGS) binds strongly to P-selectin and l -selectin − and can reduce swelling in dermatitis and arthritis . Sialic acid-containing linear polyglycerol (LPG) was also previously shown to possess immunomodulatory properties when immobilized on the cell surface .…”