Dendritic polymers for smart drug delivery applications

Interdisciplinary research platforms ensure the control of matter at the nanoscale size. Especially, polymer-based smart nanotechnology components have established their ability in delivering bioactive materials at cellular and molecular levels.

Towards this, dendritic polymeric materials have concomitantly broadened the field of biomedical applications. These polymers are classified as: (a) perfect dendrimers, (b) dendrons, (c) dendronized polymers, and (d) hyperbranched polymers.¹ Dendritic polymers are unique nanosystems because they can be expected to achieve low dispersity, nanometer dimensions, low viscosity, multiple functionality at the terminal groups, high solubility, and biocompatibility.²

Dendritic polymer architectures show significant advantages over linear polymers for many smart drug delivery applications. For example, the defined multivalency of dendrimers can be used to encapsulate or conjugate multiple drug molecules while allowing the controlled addition of targeting, imaging probes, and/or solubilizing moieties. The synergy between their multifunctionality and size on the nanoscale enables a chemical smartness along their molecular scaffold that achieves environmentally sensitive modalities.³ Moreover, the surface decoration of dendritic nanostructures confer structural benefits with consequences of a faster cellular entry, reduced macrophage uptake, targeting, and easier passage across biological barriers by transcytosis.⁴ Therefore these functional materials are expected to continue patient compliance, with progress in therapeutic targetability, and significant clinical benefits.

The articles of this themed issue highlight the recent developments of dendritic polymers as smart delivery systems. The minireview by Pavan, Thayumanavan et al. demonstrates the synergy that exists between experimental and theoretical studies to open new avenues for the use of dendrimers as versatile drug delivery systems (DOI: 10.1039/c4nr04563g). Meanwhile, Strumia and coworkers emphasize the potential of nanoparticle-cored dendrimers as functional hybrid nanocomposites (DOI: 10.1039/c4nr04438j). They discuss the most recent advances of nanoparticle-cored dendrimers in drug delivery systems and compare their behaviour with non-dendritic stabilized nanoparticles. In addition, they highlight their challenges and promising drug delivery applications. As an example, the development of hybrid dendritic-inorganic nanoparticles is described by Fahmi, González-Fernández, Fernandez-Megia et al. (DOI: 10.1039/c4nr06155a).

The great promise that dendritic polymers represent for the field of gene therapy is demonstrated by a series of articles that evaluate different dendritic architectures. Pricl et al. describe complete in silico structural and energetic characterization of the interactions of a set of carbosilane dendrimers towards two single strand oligonucleotide sequences in vitro (DOI: 10.1039/c4nr04510f). Kannan and coworkers studied hydroxyl poly(amido amine) dendrimers as gene vectors for transgene delivery to human retinal pigment epithelial cells (DOI: 10.1039/c4nr04284k). On the other hand, Liu, Peng, and collaborators discuss the implications of enhanced cellular uptake using an arginine-decorated amphiphilic poly(amido amine) dendrimer for siRNA delivery (DOI: 10.1039/c4nr04759a). Moreover, Perumal et al. present a proof of concept study of topical gene silencing by iontophoretic delivery of an antisense oligonucleotide mediated by poly(amido amine) dendrimers.

The implications of the conjugation chemistry of the tubulin-binding drug paclitaxel to dendritic polyglycerolsulfates is discussed by Welker, Calderón, and coworkers (DOI: 10.1039/c4nr04428b). The authors critically demonstrate the pitfalls of ester linkage of prodrugs to anionic dendritic polymers. Moreover, Calderón et al. described the utilization of smart imaging systems for the evaluation of uptake and probe release from dendritic polymer-based nanocarriers (DOI: 10.1039/c4nr04467c).

The development of a theranostic concept is presented by Taratula and collaborators (DOI: 10.1039/c4nr06050d). They describe dendrimer-encapsulated naphthalocyanine as a nanoplatform for near-infrared fluorescence imaging and combinatorial anticancer phototherapy.

Domínguez-Soto, Muñoz-Fernandez et al. demonstrate the use of carbosilane dendrimer to switch macrophage polarization for the acquisition of antitumor functions (DOI: 10.1039/C4NR04038D). Mignani, Majoral, and collaborators performed investigations on dendrimer space revealing solid and liquid tumor growth-inhibition by original phosphorus-based dendrimers and the corresponding monomers and dendrons with ethacrynic acid motifs (DOI: 10.1039/c4nr05983b). Such novel nanodevices shows moderate to strong antiproliferative activity against liquid and solid tumor cell lines.

In summary, the articles composing this Nanoscale themed issue validate the great potential of dendritic polymers to the delivery of bioactive molecules in different pathological circumstances. Several strategies that highlight the versatility of dendritic polymers are presented, such as drug/dye conjugation or encapsulation, gene complexation, self-assembly, etc. Novel strategies to utilize dendritic polymers as targeting moieties or therapeutic entities are also discussed. Moreover, the approaches that combine therapeutic with imaging strategies, often referred to as ‘theranostics’, strongly support the great potential of the multifunctionality of dendritic polymers for advanced biomedical applications. We hope that this themed issue encourages the development of novel dendritic platforms as perspectives for smarter approaches.

Finally, we would like to thank all contributors to this themed issue.

References

1. J. Khandare, M. Calderón, N. M. Dagia and R. Haag, Multifunctional dendritic polymers in nanomedicine: opportunities and challenges, Chem. Soc. Rev., 2012, 41(7), 2824–2848.
2. A. Kowalczuk, R. Trzcinska, B. Trzebicka, A. H. E. Müller, A. Dworak and C. B. Tsvetanov, Loading of polymer nanocarriers: Factors, mechanisms and applications, Prog. Polym. Sci., 2014, 39(1), 43–86.
3. M. Calderón, M. A. Quadir, M. Strumia and R. Haag, Functional dendritic polymer architectures as stimuli-responsive nanocarriers, Biochimie, 2010, 92(9), 1242–1251.
4. A. R. Menjoge, R. M. Kannan and D. A. Tomalia, Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications, Drug Discovery Today, 2010, 15(5–6), 171–185.

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