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Review
. 2017 Aug 23;22(9):1401.
doi: 10.3390/molecules22091401.

Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy

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Free PMC article
Review

Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy

Livia Palmerston Mendes et al. Molecules. .
Free PMC article

Abstract

Dendrimers are highly branched polymers with easily modifiable surfaces. This makes them promising structures for functionalization and also for conjugation with drugs and DNA/RNA. Their architecture, which can be controlled by different synthesis processes, allows the control of characteristics such as shape, size, charge, and solubility. Dendrimers have the ability to increase the solubility and bioavailability of hydrophobic drugs. The drugs can be entrapped in the intramolecular cavity of the dendrimers or conjugated to their functional groups at their surface. Nucleic acids usually form complexes with the positively charged surface of most cationic dendrimers and this approach has been extensively employed. The presence of functional groups in the dendrimer's exterior also permits the addition of other moieties that can actively target certain diseases and improve delivery, for instance, with folate and antibodies, now widely used as tumor targeting strategies. Dendrimers have been investigated extensively in the medical field, and cancer treatment is one of the greatest areas where they have been most used. This review will consider the main types of dendrimer currently being explored and how they can be utilized as drug and gene carriers and functionalized to improve the delivery of cancer therapy.

Keywords: PAMAM; PLL; PPI; cancer; dendrimers; drug; nucleic acid.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of third generation dendrimers. (A) PAMAM with ethylenediamine core; (B) PPI with 1,4-diaminobutane core; (C) PLL with Boc-l-Lys(Boc)-OH benzhydrylamide core. Illustrations generated by ChemDraw Professional Version 16.0.1.4.
Figure 2
Figure 2
Schematic representation of 3G PAMAM and examples of how dendrimers can interact with drugs and nucleic acid. Also, possible surface modifications that increase tumor specificity. Illustration generated by ChemDraw Professional Version 16.0.1.4.
Figure 3
Figure 3
Schematic representation of a PAMAM dendrimer as drug and/or nucleic acid delivery platforms. Dendrimers are internalized by the cell into endosomal vesicles. Due to the lower pH inside the endosome (pH 5.5) and the abundant number of tertiary amines in the dendrimers, the “proton sponge effect” is achieved. It promotes the influx of ions into the vesicles, which eventually leads to rupture of the endosomal wall and release of the cargo intracellularly. Depending on the payload, the effect will be exerted in the cytoplasm or in the nucleus.

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References

    1. Liu M., Fréchet J.M.J. Designing dendrimers for drug delivery. Pharm. Sci. Technol. Today. 1999;2:393–401. doi: 10.1016/S1461-5347(99)00203-5. - DOI - PubMed
    1. Svenson S., Tomalia D.A. Dendrimers in biomedical applications—Reflections on the field. Adv. Drug Deliv. Rev. 2012;64:102–115. doi: 10.1016/j.addr.2012.09.030. - DOI
    1. Lee C.C., MacKay J.A., Frechet J.M.J., Szoka F.C. Designing dendrimers for biological applications. Nat. Biotechnol. 2005;23:1517–1526. doi: 10.1038/nbt1171. - DOI - PubMed
    1. Kesharwani P., Jain K., Jain N.K. Dendrimer as nanocarrier for drug delivery. Prog. Polym. Sci. 2014;39:268–307. doi: 10.1016/j.progpolymsci.2013.07.005. - DOI
    1. Kalomiraki M., Thermos K., Chaniotakis N.A. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications. Int. J. Nanomed. 2016;11:1–12. - PMC - PubMed
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