pH-Sensitive Dendrimersomes of Hybrid Triazine-Carbosilane Dendritic Amphiphiles-Smart Vehicles for Drug Delivery

Supramolecular constructions of amphiphilic dendritic molecules are promising vehicles for anti-cancer drug delivery due to the flexibility of their architecture, high drug loading capacity and avoiding off-target effects of a drug. Herein, we report a new class of amphiphilic dendritic species—triazine-carbosilane dendrons readily self-assembling into pH-sensitive dendrimersomes. The dendrimersomes efficiently encapsulate anticancer drugs doxorubicin and methotrexate. Chemodrug-loaded dendrimersomes have dose-related cytotoxic activity against leukaemia cell lines 1301 and K562. Our findings suggest that triazine-carbosilane dendrimersomes are prospective drug carriers for anti-cancer therapy

Supramolecular Self‐Associations of Amphiphilic Dendrons and Their Properties

International audienceThis review presents precisely defined amphiphilic dendrons, their self-association properties, and their different uses. Dendrons, also named dendritic wedges, are composed of a core having two different types of functions, of which one type is used for growing or grafting branched arms, generally multiplied by 2 at each layer by using 1→2 branching motifs. A large diversity of structures has been already synthesized. In practically all cases, their synthesis is based on the synthesis of known dendrimers, such as poly(aryl ether), poly(amidoamine) (in particular PAMAM), poly(amide) (in particular poly(L-lysine)), 1→3 branching motifs (instead of 1→2), poly(alkyl ether) (poly(glycerol) and poly(ethylene glycol)), poly(ester), and those containing main group elements (poly(carbosilane) and poly(phosphorhydrazone)). In most cases, the hydrophilic functions are on the surface of the dendrons, whereas one or two hydrophobic tails are linked to the core. Depending on the structure of the dendrons, and on the experimental conditions used, the amphiphilic dendrons can self-associate at the air-water interface, or form micelles (eventually tubular, but most generally spherical), or form vesicles. These associated dendrons are suitable for the encapsulation of low-molecular or macromolecular bioactive entities to be delivered in cells. This review is organized depending on the nature of the internal structure of the amphiphilic dendrons (aryl ether, amidoamine, amide, quaternary carbon atom, alkyl ether, ester, main group element). The properties issued from their self-associations are described all along the review

Phosphorus Dendrimers as Physical Hydrogels and Their Properties

Article électroniqueThis entry is adapted from 10.3390/jcs7010026Hydrogels are hydrophilic, three-dimensional networks able to imprison large amounts of water and are largely used in pharmaceutical formulations. Hydrogels are frequently obtained from hydrophilic polymers, either natural, biohybrid, or synthetic. Phosphorus dendrimers possessing high multivalency provide the favorable positioning of functional groups at the surface, as well as cavities, in the three-dimensional organization of the scaffold and, therefore, can be considered potential gelators. The internal structure of phosphorus dendrimers is hydrophobic, whereas their terminal functions can be positively or negatively charged; thus, the whole structure becomes amphiphilic

Single-Component Physical Hydrogels of Dendritic Molecules

International audienceHydrogels are hydrophilic, three-dimensional networks able to imprison large amounts of water and are largely used in pharmaceutical formulations. Hydrogels are frequently obtained from hydrophilic polymers, either natural, biohybrid, or synthetic. Owing to their peculiar structure, dendrimers can be considered prospective building blocks for hydrogel networks. This review gathers the use of different types of amphiphilic dendritic structures able to generate physical hydrogels alone. Such dendritic structures comprise dendrimers, Janus dendrimers, and dendrons. The first part concerns different types of positively charged phosphorus dendrimers used to generate hydrogels, which are also suitable to form fibers, and for encapsulating diverse substances, or forming complexes with genetic materials for their slow delivery. The second part concerns PAMAM dendrimers functionalized with collagen mimetics. The third part concerns amphiphilic Janus dendrimers, whereas the fourth part displays different types of amphiphilic dendrons and their use, in particular in the fields of materials and drug delivery

Topological Aspects of the Design of Nanocarriers for Therapeutic Peptides and Proteins

Supramolecular chemistry holds great potential for the design of versatile and safe carriers for therapeutic proteins and peptides. Nanocarriers can be designed to meet specific criteria for given application (exact drug, administration route, target tissue, etc.). However, alterations in the topology of formulation components can drastically change their activity. This is why the supramolecular topology of therapeutic nanoconstructions has to be considered. Herein, we discuss several topological groups used for the design of nanoformulations for peptide and protein delivery: modification of polypeptide chains by host-guest interactions; packaging of proteins and peptides into liposomes; complexation and conjugation with dendrimers. Each topological type has its own advantages and disadvantages, so careful design of nanoformulations is needed. Ideally, each case where nanomedicine is needed requires a therapeutic construction specially created for that taking into account features of the administration route, target tissue, or organ, properties of a drug, its bioavailability, etc. The wide number of studies in the field of protein delivery by supramolecular and nanocarriers for proteins and peptides evidence their increasing potential for different aspects of the innovative medicine. Although significant progress has been achieved in the field, there are several remaining challenges to be overcome in future

Dendriplex-Impregnated Hydrogels With Programmed Release Rate

International audienceHydrogels are biocompatible matrices for local delivery of nucleic acids; however, functional dopants are required to provide efficient delivery into cells. In particular, dendrimers, known as robust nucleic acid carriers, can be used as dopants. Herein, we report the first example of impregnating neutral hydrogels with siRNA–dendrimer complexes. The surface chemistry of dendrimers allows adjusting the release rate of siRNA-containing complexes. This methodology can bring new materials for biomedical applications

Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity

International audienceDendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi-micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 µM for copper-containing dendron and 11–15 µM for gold-containing dendron) in comparison with temozolomide (IC50 >100 µM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron-based nanoformulations as antitumor entities

Recent Advances in Nucleic Acid Targeting Probes and Supramolecular Constructs Based on Pyrene-Modified Oligonucleotides

In this review, we summarize the recent advances in the use of pyrene-modified oligonucleotides as a platform for functional nucleic acid-based constructs. Pyrene is of special interest for the development of nucleic acid-based tools due to its unique fluorescent properties (sensitivity of fluorescence to the microenvironment, ability to form excimers and exciplexes, long fluorescence lifetime, high quantum yield), ability to intercalate into the nucleic acid duplex, to act as a π-π-stacking (including anchoring) moiety, and others. These properties of pyrene have been used to construct novel sensitive fluorescent probes for the sequence-specific detection of nucleic acids and the discrimination of single nucleotide polymorphisms (SNPs), aptamer-based biosensors, agents for binding of double-stranded DNAs, and building blocks for supramolecular complexes. Special attention is paid to the influence of the design of pyrene-modified oligonucleotides on their properties, i.e., the structure-function relationships. The perspectives for the applications of pyrene-modified oligonucleotides in biomolecular studies, diagnostics, and nanotechnology are discussed

Dendrimer-Mediated Delivery of DNA and RNA Vaccines

DNA and RNA vaccines (nucleic acid-based vaccines) are a promising platform for vaccine development. The first mRNA vaccines (Moderna and Pfizer/BioNTech) were approved in 2020, and a DNA vaccine (Zydus Cadila, India), in 2021. They display unique benefits in the current COVID-19 pandemic. Nucleic acid-based vaccines have a number of advantages, such as safety, efficacy, and low cost. They are potentially faster to develop, cheaper to produce, and easier to store and transport. A crucial step in the technology of DNA or RNA vaccines is choosing an efficient delivery method. Nucleic acid delivery using liposomes is the most popular approach today, but this method has certain disadvantages. Therefore, studies are actively underway to develop various alternative delivery methods, among which synthetic cationic polymers such as dendrimers are very attractive. Dendrimers are three-dimensional nanostructures with a high degree of molecular homogeneity, adjustable size, multivalence, high surface functionality, and high aqueous solubility. The biosafety of some dendrimers has been evaluated in several clinical trials presented in this review. Due to these important and attractive properties, dendrimers are already being used to deliver a number of drugs and are being explored as promising carriers for nucleic acid-based vaccines. This review summarizes the literature data on the development of dendrimer-based delivery systems for DNA and mRNA vaccines