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Pharmaceutics
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Dendrimer-Based Nanomedicine
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Dendrimer-Based Nanomedicine

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 November 2020) | Viewed by 13321

Special Issue Editor

Prof. Maksim Ionov

E-Mail Website
Guest Editor
Department of General Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
Interests: nanomedicine; drug delivery; nanoparticles; biological systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the past decades, dendrimers have gained popularity in the field of nanomedicine. Dendrimers are polymeric molecules with a well-defined shape and size that can successfully be used in gene therapy, medical imaging, and immunology, which are used primarily as nanocarriers for the delivery of drugs or genes to target cells. Dendrimers are more efficient than liposomes, linear polymers, or viral vectors in transferring of many kinds of biomolecules. In this regard, the mechanisms of interaction between dendrimers and biological systems have now become of significant interest, with an abundance of articles now being reported in the literature.

For this Special Issue, we invite submissions of manuscripts focusing on the dendritic nanoparticles that could be applied in biomedicine as new nanotherapeutic agents, especially in the field of drug and gene delivery.

Prof. Maksim Ionov
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dendrimer
  • Dendriplex
  • Drug carrier
  • Gene delivery
  • Interaction
  • Antiviral
  • Toxicity
  • Targeting delivery
  • Biomedicine

Published Papers (5 papers)

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Research

20 pages, 4965 KiB  
Article
Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties
by Maciej Cieślak, Damian Ryszawy, Maciej Pudełek, Magdalena Urbanowicz, Maja Morawiak, Olga Staszewska-Krajewska, Jarosław Czyż and Zofia Urbańczyk-Lipkowska
Pharmaceutics 2020, 12(11), 1106; https://doi.org/10.3390/pharmaceutics12111106 - 18 Nov 2020
Cited by 3 | Viewed by 2346
Abstract
(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards [...] Read more.
(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells’ phenotype. Full article
(This article belongs to the Special Issue Dendrimer-Based Nanomedicine)
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14 pages, 3477 KiB  
Article
Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells
by Natalia Sanz del Olmo, Marcin Holota, Sylwia Michlewska, Rafael Gómez, Paula Ortega, Maksim Ionov, Francisco Javier de la Mata and Maria Bryszewska
Pharmaceutics 2020, 12(8), 727; https://doi.org/10.3390/pharmaceutics12080727 - 02 Aug 2020
Cited by 20 | Viewed by 2994
Abstract
Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with [...] Read more.
Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with anticancer activity that achieves a synergistic effect with siRNA. Cationic carbosilane dendrimers have proved to be powerful tools as non-viral vectors for siRNA in cancer treatment, and their activity might be potentiated by the inclusion of metallic complexes in its dendritic structure. We have herein explored the interaction between Schiff-base carbosilane copper (II) metallodendrimers, and pro-apoptotic siRNAs. The nanocomplexes formed by metallodendrimers and different siRNA have been examined for their zeta potential and size, and by transmission electron microscopy, fluorescence polarisation, circular dichroism, and electrophoresis. The internalisation of dendriplexes has been estimated by flow cytometry and confocal microscopy in a human breast cancer cell line (MCF-7), following the ability of these metallodendrimers to deliver the siRNA into the cell. Finally, in vitro cell viability experiments have indicated effective interactions between Cu (II) dendrimers and pro-apoptotic siRNAs: Mcl-1 and Bcl-2 in breast cancer cells. Combination of the first-generation derivatives with chloride counterions and with siRNA increases the anticancer activity of the dendriplex constructs and makes them a promising non-viral vector. Full article
(This article belongs to the Special Issue Dendrimer-Based Nanomedicine)
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15 pages, 4802 KiB  
Article
A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids
by Bhairavi Srinageshwar, Maria Florendo, Brittany Clark, Kayla Johnson, Nikolas Munro, Sarah Peruzzaro, Aaron Antcliff, Melissa Andrews, Alexander Figacz, Douglas Swanson, Gary L. Dunbar, Ajit Sharma and Julien Rossignol
Pharmaceutics 2020, 12(7), 619; https://doi.org/10.3390/pharmaceutics12070619 - 03 Jul 2020
Cited by 4 | Viewed by 2750
Abstract
Drug delivery to the brain is highly hindered by the presence of the blood–brain barrier (BBB), which prevents the entry of many potential drugs/biomolecules into the brain. One of the current strategies to achieve gene therapy for neurodegenerative diseases involves direct injection of [...] Read more.
Drug delivery to the brain is highly hindered by the presence of the blood–brain barrier (BBB), which prevents the entry of many potential drugs/biomolecules into the brain. One of the current strategies to achieve gene therapy for neurodegenerative diseases involves direct injection of a viral vector into the brain. There are various disadvantages of viral vectors, including limitations of cargo size and safety concerns. Nanomolecules, such as dendrimers, serve as an excellent alternative to viral delivery. In this study, as proof-of-concept, we used a surface-modified dendrimer complex and delivered large plasmids to cells in vitro and in vivo in healthy rats via intracranial injection. The dendrimers were biodegradable by chemicals found within cells and toxicity assays revealed that the modified dendrimers were much less toxic than unmodified amine-surface dendrimers. As mentioned in our previous publication, these dendrimers with appropriately modified surfaces are safe, can deliver large plasmids to the brain, and can overcome the cargo size limitations associated with viral vectors. The biocompatibility of this dendritic nanomolecule and the ability to finely tune its surface chemistry provides a gene delivery system that could facilitate future in vivo cellular reprograming and other gene therapies. Full article
(This article belongs to the Special Issue Dendrimer-Based Nanomedicine)
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15 pages, 2275 KiB  
Article
Cationic Dendrimer G2-S16 Inhibits Herpes Simplex Type 2 Infection and Protects Mice Vaginal Microbiome
by Carlos Guerrero-Beltrán, Inmaculada Garcia-Heredia, Rafael Ceña-Diez, Ignacio Rodriguez-Izquierdo, María Jesús Serramía, Francisco Martinez-Hernandez, Mónica Lluesma-Gomez, Manuel Martinez-Garcia and María Ángeles Muñoz-Fernández
Pharmaceutics 2020, 12(6), 515; https://doi.org/10.3390/pharmaceutics12060515 - 04 Jun 2020
Cited by 9 | Viewed by 2279
Abstract
The G2-S16 polyanionic carbosilane dendrimer is a promising microbicide that inhibits HSV-2 infection in vitro and in vivo in mice models. This G2-S16 dendrimer inhibits HSV-2 infection even in the presence of semen. Murine models, such as BALB/c female mice, are generally used [...] Read more.
The G2-S16 polyanionic carbosilane dendrimer is a promising microbicide that inhibits HSV-2 infection in vitro and in vivo in mice models. This G2-S16 dendrimer inhibits HSV-2 infection even in the presence of semen. Murine models, such as BALB/c female mice, are generally used to characterize host-pathogen interactions within the vaginal tract. However, the composition of endogenous vaginal flora remains largely undefined with modern microbiome analyses. It is important to note that the G2-S16 dendrimer does not change healthy mouse vaginal microbiome where Pseudomonas (10.2–79.1%) and Janthinobacterium (0.7–13%) are the more abundant genera. The HSV-2 vaginally infected female mice showed a significant microbiome alteration because an increase of Staphylococcus (up to 98.8%) and Escherichia (30.76%) levels were observed becoming these bacteria the predominant genera. BALB/c female mice vaginally-treated with the G2-S16 dendrimer and infected with the HSV-2 maintained a healthy vaginal microbiome similar to uninfected female mice. Summarizing, the G2-S16 polyanionic carbosilane dendrimer inhibits the HSV-2 infection in the presence of semen and prevents the alteration of mice female vaginal microbiome. Full article
(This article belongs to the Special Issue Dendrimer-Based Nanomedicine)
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23 pages, 7509 KiB  
Article
Stepwise Glucoheptoamidation of Poly(Amidoamine) Dendrimer G3 to Tune Physicochemical Properties of the Potential Drug Carrier: In Vitro Tests for Cytisine Conjugates
by Anna Czerniecka-Kubicka, Piotr Tutka, Marek Pyda, Małgorzata Walczak, Łukasz Uram, Maria Misiorek, Ewelina Chmiel and Stanisław Wołowiec
Pharmaceutics 2020, 12(5), 473; https://doi.org/10.3390/pharmaceutics12050473 - 22 May 2020
Cited by 11 | Viewed by 2444
Abstract
Third-generation poly(amidoamine) dendrimer (PAMAM) was modified by stepwise primary amine group amidation with d-glucoheptono-1,4-lactone. The physicochemical properties of the conjugates—size, ζ potential in lysosomal pH 5 and in neutral aqueous solutions, as well as intramolecular dynamics by differential scanning calorimetry—were determined. Internalization [...] Read more.
Third-generation poly(amidoamine) dendrimer (PAMAM) was modified by stepwise primary amine group amidation with d-glucoheptono-1,4-lactone. The physicochemical properties of the conjugates—size, ζ potential in lysosomal pH 5 and in neutral aqueous solutions, as well as intramolecular dynamics by differential scanning calorimetry—were determined. Internalization and toxicity of the conjugates against normal human fibroblasts BJ were monitored in vitro in order to select an appropriate carrier for a drug delivery system. It was found that initial glucoheptoamidation (up to 1/3 of amine groups of neat dendrimers available) resulted in increase of conjugate size and ζ potential. Native or low substituted dendrimer conjugates accumulated efficiently in fibroblast cells at nontoxic 1 µM concentration. Further substitution of dendrimer caused consistent decrease of size and ζ potential, cell accumulation, and toxicity. All dendrimers are amorphous at 36.6 °C as determined by differential scanning calorimetry (DSC). The optimized dendrimer, half-filled with glucoheptoamide substituents, was applied as carrier bearing two covalently attached cytisine molecules: a rigid and hydrophobic alkaloid. The conjugate with 2 cytisine and 16 glucoheptoamide substituents showed fast accumulation and no toxicity up to 200 µM concentration. The half-glucoheptoamidated PAMAM dendrimer was selected as a promising anticancer drug carrier for further applications. Full article
(This article belongs to the Special Issue Dendrimer-Based Nanomedicine)
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