The Present and the Future of Degradable Dendrimers and Derivatives in Theranostics

Abstract

Interest in dendrimer-based nanomedicines has been growing recently, as it is possible to precisely manipulate the molecular weight, chemical composition, and surface functionality of dendrimers, tuning their properties according to the desired biomedical application. However, one important concern about dendrimer-based therapeutics remains-the nondegradability under physiological conditions of the most commonly used dendrimers. Therefore, biodegradable dendrimers represent an attractive class of nanomaterials, since they present advantages over conventional nondegradable dendrimers regarding the release of the loaded molecules and the prevention of bioaccumulation of synthetic materials and subsequent cytotoxicity. Here, we present an overview of the state-of-the-art of the design of biodegradable dendritic structures, with particular focus on the hurdles regarding the use of these as vectors of drugs and nucleic acids, as well as macromolecular contrast agents.

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

“…Recently, several of us (Mignani, Shi, Rodrigues, Tomas and Majoral) have proposed a simple guideline to scientists (chemists, biologists, pharmacologists, engineers, and physicians) working in the dendrimer field based on several translational requirements to move towards an Investigational New Drug application (IND), which is an evaluation of the safety profile before initiating clinical trials [92]. In addition, Mignani and Majoral have defined the term dendrimer space concept as an approach that affords a new paradigm of thought for medicinal chemists and opens new and promising avenues for the identification of original and biocompatible dendrimers and dendrimer-based drugs [93], which have been analyzed by Leiro et al [94] regarding the future of degradable dendrimers in theranostics.…”

Dendritic hexadecapeptide as a cathepsin B degradable carrier for delivery of HSP90 inhibitor

“…4A). DGFLGAHGDM 3 13.1 ± 0.5 * --EDTA(GFLGAHGDM) 4 13.8 ± 3.9 * 3.4 ± 0.5 # 3.5 ± 0.0 # Significant difference (p <0.02) compared to 48 h value for the same compound. * Significant difference (p <0.005) compared to GFLGAHGDM.…”

“…3 However, one of the limitations of currently used dendrimers is that they are nondegradable. 4 Because degradable systems are more biocompatible than their nondegradable counterparts 5 there is a great interest in developing physiologically degradable dendrimers. A few degradable dendrimers reported so far have relied on the chemical hydrolysis in a biological environment; 6 majority of them having ester bonds that can degrade nonspecifically.…”

“…A few degradable dendrimers reported so far have relied on the chemical hydrolysis in a biological environment; 6 majority of them having ester bonds that can degrade nonspecifically. 4 In contrast, using dendrimers that can be degraded by enzymes is an attractive choice because of degradation specificity associated with the selected enzyme. Enzymatic trigger has been used successfully for releasing the drug from a polymeric backbone.…”

Biodegradable PEG–dendritic block copolymers: synthesis and biofunctionality assessment as vectors of siRNA

“…[23][24][25][26] To overcome these hurdles, a number of teams are focusing on the design of biodegradable dendritic structures. 27 Indeed, biodegradable materials that, under physiological conditions, degrade in time into smaller fragments (which can be excreted or eliminated through metabolic pathways), are expected to overcome the risk of complications associated with the long-term presence in tissues of non-degradable synthetic materials. [28][29][30][31][32] Moreover, in gene therapy applications, biodegradable vectors are expected to facilitate the intracellular release of the NA from the dendriplex and so, ensure higher transfection efficiencies.…”