Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

doi:10.3390/pharmaceutics12090874

Review

. 2020 Sep 14;12(9):874.

doi: 10.3390/pharmaceutics12090874.

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

Miguel Ángel Ortega^{1

2

3

4}, Alberto Guzmán Merino¹, Oscar Fraile-Martínez¹, Judith Recio-Ruiz⁵, Leonel Pekarek¹, Luis G Guijarro^{6

7}, Natalio García-Honduvilla^{1

2

4}, Melchor Álvarez-Mon^{1

2

4

8}, Julia Buján^{1

2

3

4}, Sandra García-Gallego^{2

5}

Affiliations

¹ Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.
² Institute Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain.
³ Tumour Registry, Pathological Anatomy Service, University Hospital Príncipe de Asturias, 28805 Alcalá de Henares, Spain.
⁴ University Center for the Defense of Madrid (CUD-ACD), 28047 Madrid, Spain.
⁵ Department of Organic and Inorganic Chemistry, Faculty of Sciences, and Research Institute in Chemistry "Andrés M. del Río" (IQAR), University of Alcalá, 28801 Alcalá de Henares, Spain.
⁶ Department of Systems Biology, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.
⁷ Networking Research Centre on Hepatic and Digestive Diseases (CIBER-EHD), 28029 Madrid, Spain.
⁸ Immune System Diseases-Rheumatology, Oncology and Medicine Service, University Hospital Príncipe de Asturias, 28805 Alcalá de Henares, Madrid, Spain.

PMID: 32937793
PMCID: PMC7560085
DOI: 10.3390/pharmaceutics12090874

Review

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

Miguel Ángel Ortega et al. Pharmaceutics. 2020.

. 2020 Sep 14;12(9):874.

doi: 10.3390/pharmaceutics12090874.

Authors

Affiliations

¹ Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.
² Institute Ramón y Cajal for Health Research (IRYCIS), 28034 Madrid, Spain.
³ Tumour Registry, Pathological Anatomy Service, University Hospital Príncipe de Asturias, 28805 Alcalá de Henares, Spain.
⁴ University Center for the Defense of Madrid (CUD-ACD), 28047 Madrid, Spain.
⁵ Department of Organic and Inorganic Chemistry, Faculty of Sciences, and Research Institute in Chemistry "Andrés M. del Río" (IQAR), University of Alcalá, 28801 Alcalá de Henares, Spain.
⁶ Department of Systems Biology, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.
⁷ Networking Research Centre on Hepatic and Digestive Diseases (CIBER-EHD), 28029 Madrid, Spain.
⁸ Immune System Diseases-Rheumatology, Oncology and Medicine Service, University Hospital Príncipe de Asturias, 28805 Alcalá de Henares, Madrid, Spain.

PMID: 32937793
PMCID: PMC7560085
DOI: 10.3390/pharmaceutics12090874

Abstract

Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundless possibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented. Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectious diseases and many other health issues.

Keywords: amoeba; bacteria; dendrimer; fungi; infection; nanoparticle; parasite; prion; virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Scheme depicting the traditional synthetic approaches to dendrimers. (A) Divergent growth approach, inside-out strategy from the core. (B) Convergent growth approach, outside-in strategy from the terminal groups.

**Figure 2**
Overview of the most common dendritic families for biomedical applications, depicting the structure of second generation dendrimers. (A) Poly(amino amide) (PAMAM). (B) Poly(propylene imine) (PPI). (C) Poly(L-lysine) (PLL). (D) Carbosilane (CBS). (E) Poly(phosphorhydrazone) (PPH). (F) Bis-MPA polyester. The core is highlighted in pink, the terminal groups in blue.

**Figure 3**
Scheme of a second-generation dendrimer and its interactions with multiple agents, including covalently-bound drugs (1), encapsulated drugs (2), covalently-bound diagnostic agents (3), antibodies (4), poly(ethylene glycol) (5), and electrostatic interaction with nucleic acids (6).

**Figure 4**
Proposed mechanism for the antiviral effect (**top**, through blockage of viral or host cell receptors) and antibacterial activity (**bottom**, through electrostatic interaction and subsequent disruption of bacteria membrane) of dendrimers. Reprinted with permission from Ref. [57], copyright © 2012 Wiley Periodicals, Inc.

**Figure 5**
Examples of dendritic materials with potent antiviral activity and representative EC₅₀/IC₅₀ values. (A) SPL7013 dendrimer (VivaGel^®), against SARS-CoV-2; (B) dendronized glycofullerene conjugated to multiwall carbon nanotubes, towards Ebola virus; (C) dendronized glycofullerene nanoballs, efficient towards Zika and Dengue viruses. Reprinted with permission from Refs. [84] (B) and [85] (C), Copyright 2018 and 2019, American Chemical Society.

**Figure 6**
Examples of the antimicrobial activity of different dendritic molecules. (A) Inhibition of *Pseudomonas aeruginosa* biofilms by glycopeptide dendrimer FD2. Figure reprinted from ref. [100], Copyright 2008, with permission from Elsevier. (B) Effect on *Candida albicans* biofilm after treatment with a peptide dendrimer (16 µg/mL). Figure reprinted from Ref. [102], Copyright 2015, with permission from Elsevier. (C) Decrease in the number of *Leishmania Major* parasites in mice kidney after treatment with a dendritic polyester (A50) and amphotericin B loaded dendrimer (AD50). Figure reprinted by permission from ref. [103], Springer Nature, Copyright 2018. (D) Alterations of *Acanthamoeba polyphaga* trophozoites after treatment with a carbosilane dendrimer (2 mg/L). Figure reprinted from ref. [104]. (E) Evolution of PrP^Sc levels in ScN2a cells after treatment with a G4 PPH dendrimer (10 µg/mL). Reprinted with permission from Ref. [105], SGM, Copyright 2004.

**Figure 7**
Mechanism to detect malaria antigens using the coumarin-derived dendrimer-based fluorescence-linked immunosorbent assay (FLISA) [145].

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References

1. Zorrilla-Vaca A., Escandón-Vargas K. The importance of infection control and prevention in anesthesiology. Colomb. J. Anesthesiol. 2017;45:69–77. doi: 10.1016/j.rcae.2017.10.001. - DOI
1. Ellwanger J.H., Kaminski V.d.L., Chies J.A.B. Emerging infectious disease prevention: Where should we invest our resources and efforts? J. Infect. Public Health. 2019;12:313–316. doi: 10.1016/j.jiph.2019.03.010. - DOI - PubMed
1. Martínez A.J. Las enfermedades infecciosas emergentes y reemergentes, un tema de interés para todos. Rev. Med. Electron. 2014;36:537–539.
1. Altizer S., Ostfeld R.S., Johnson P.T.J., Kutz S., Harvell C.D. Climate change and infectious diseases: From evidence to a predictive framework. Science. 2013;341:514–519. doi: 10.1126/science.1239401. - DOI - PubMed
1. Patz J.A., Frumkin H., Holloway T., Vimont D.J., Haines A. Climate change: Challenges and opportunities for global health. JAMA. 2014;312:1565–1580. doi: 10.1001/jama.2014.13186. - DOI - PMC - PubMed

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[1] Zorrilla-Vaca A., Escandón-Vargas K. The importance of infection control and prevention in anesthesiology. Colomb. J. Anesthesiol. 2017;45:69–77. doi: 10.1016/j.rcae.2017.10.001. - DOI

[2] Zorrilla-Vaca A., Escandón-Vargas K. The importance of infection control and prevention in anesthesiology. Colomb. J. Anesthesiol. 2017;45:69–77. doi: 10.1016/j.rcae.2017.10.001. - DOI

[3] Ellwanger J.H., Kaminski V.d.L., Chies J.A.B. Emerging infectious disease prevention: Where should we invest our resources and efforts? J. Infect. Public Health. 2019;12:313–316. doi: 10.1016/j.jiph.2019.03.010. - DOI - PubMed

[4] Ellwanger J.H., Kaminski V.d.L., Chies J.A.B. Emerging infectious disease prevention: Where should we invest our resources and efforts? J. Infect. Public Health. 2019;12:313–316. doi: 10.1016/j.jiph.2019.03.010. - DOI - PubMed

[5] Martínez A.J. Las enfermedades infecciosas emergentes y reemergentes, un tema de interés para todos. Rev. Med. Electron. 2014;36:537–539.

[6] Martínez A.J. Las enfermedades infecciosas emergentes y reemergentes, un tema de interés para todos. Rev. Med. Electron. 2014;36:537–539.

[7] Altizer S., Ostfeld R.S., Johnson P.T.J., Kutz S., Harvell C.D. Climate change and infectious diseases: From evidence to a predictive framework. Science. 2013;341:514–519. doi: 10.1126/science.1239401. - DOI - PubMed

[8] Altizer S., Ostfeld R.S., Johnson P.T.J., Kutz S., Harvell C.D. Climate change and infectious diseases: From evidence to a predictive framework. Science. 2013;341:514–519. doi: 10.1126/science.1239401. - DOI - PubMed

[9] Patz J.A., Frumkin H., Holloway T., Vimont D.J., Haines A. Climate change: Challenges and opportunities for global health. JAMA. 2014;312:1565–1580. doi: 10.1001/jama.2014.13186. - DOI - PMC - PubMed

[10] Patz J.A., Frumkin H., Holloway T., Vimont D.J., Haines A. Climate change: Challenges and opportunities for global health. JAMA. 2014;312:1565–1580. doi: 10.1001/jama.2014.13186. - DOI - PMC - PubMed

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Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

Affiliations

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

Authors

Affiliations

Abstract

Conflict of interest statement

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