Dendrimers: A Themed Issue in Honor of Professor Donald A. Tomalia on the Occasion of His 85th Birthday, Recognizing His Outstanding Achievements in Advancing the Field of Dendrimers.

As the main pioneer in the field of dendrimers, a term that he coined in 1985 in reference to their tree-like structure, Prof. Donald A. Tomalia has inspired several generations of researchers worldwide [.

Diverse Approaches for the Difunctionalization of PPH Dendrimers, Precise Versus Stochastic: How Does this Influence Catalytic Performance?

Random difunctionalization of dendrimer surfaces, frequently employed in biological applications, provides the advantage of dual functional groups through a synthetic pathway that is simpler compared to precise difunctionalization. However, is the random difunctionalization as efficient as the precise difunctionalization on the surface of dendrimers? This question is unanswered to date because most dendrimer families face challenges in achieving precise functionalization. Polyphosphorhydrazone (PPH) dendrimers present a unique opportunity to obtain precise difunctionalization at each terminal branching point.

A water-soluble polyphosphorhydrazone Janus dendrimer built by "click" chemistry as support for Ru-complexes in catalysis.

The field of supported catalysis has experienced increased attention with respect to the development of novel architectures for immobilizing catalytic species, aiming to maintain or enhance their activity while facilitating the easy recovery and reuse of the active moiety. Dendrimers have been identified as promising candidates capable of imparting such properties to catalysts through selective functionalization. The present study details the synthesis of two polyphosphorhydrazone (PPH) dendrons, each incorporating azide or acetylene groups at the core for subsequent coupling through "click" triazole chemistry.

Dendritic Pyridine-Imine Copper Complexes as Metallo-Drugs.

Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted much interest. Among the other metals that have been examined for potential applications as anticancer agents is copper. The interest in copper was recently boosted by the discovery of cuproptosis, a recently evidenced form of cell death mediated by copper.

Two-Photon Absorbing Dendrimers and Their Properties-An Overview.

This review describes the two-photon absorption properties of dendrimers, which are arborescent three-dimensional macromolecules differing from polymers by their perfectly defined structure. The two-photon absorption process is a third order non-linear optical property that is attractive because it can be used in a wide range of applications. In this review, dendrimers that were studied for their two-photon absorption properties are first described.

Carboranylphosphines: B9-Substituted Derivatives with Enhanced Reactivity for Anchoring to Dendrimers.

Invited for the cover of this issue are the groups and colleagues of Anne-Marie Caminade at the CNRS and University of Toulouse, Evamarie Hey-Hawkins at Leipzig University, and Agustí Lledós from the Autonomous University of Barcelona. The image depicts birds crowned by a carborane competing for access to food, to illustrate the steric hindrance encountered when grafting carboranes to dendrimers (artwork by Dr. Christoph Selg).

Carboranylphosphines: B9-Substituted Derivatives with Enhanced Reactivity for the Anchoring to Dendrimers.

Several ortho-carboranes bearing a phenoxy or a phenylamino group in the B9 position were prepared employing various protection and deprotection strategies. Following established protocols, dendritic compounds were synthesized from a hexachlorocyclotriphosphazene or thiophosphoryl chloride core, and possible anchoring options for the B9-substituted ortho-carboranes were investigated experimentally and theoretically (DFT). Furthermore, 1- or 1,2-phosphanyl-substituted carborane derivatives were obtained.

Unsymmetrical Low-Generation Cationic Phosphorus Dendrimers as a Nonviral Vector to Deliver MicroRNA for Breast Cancer Therapy.

The development of nonviral dendritic polymers with a simple molecular backbone and great gene delivery efficiency to effectively tackle cancer remains a great challenge. Phosphorus dendrimers or dendrons are promising vectors due to their structural uniformity, rigid molecular backbones, and tunable surface functionalities. Here, we report the development of a new low-generation unsymmetrical cationic phosphorus dendrimer bearing 5 pyrrolidinium groups and one amino group as a nonviral gene delivery vector.

"Click" Chemistry for the Functionalization of Graphene Oxide with Phosphorus Dendrons: Synthesis, Characterization and Preliminary Biological Properties.

Two families of phosphorhydrazone dendrons having either an azide or an alkyne linked to the core and diverse types of pyridine derivatives as terminal functions have been synthesized and characterized. These dendrons were grafted via click reaction to graphene oxide (GO) functionalized with either alkyne or azide functions, respectively. The resulting modified-GO and GO-dendrons materials have been characterized by Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), and Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses.

Dendritic Structures Functionalized with Boron Clusters, in Particular Carboranes, and Their Biological Properties.

The presence of a large number of boron atoms in boron clusters make them attractive tools for the treatment of cancer using boron neutron capture therapy (BNCT). Since the quantity of boron atoms present in the target cell directly affects the effectiveness of BNCT, the idea of gathering a high number of boron atoms in a single entity has emerged many years ago. In this perspective, using hyper-branched macromolecules such as dendrimers appears as an interesting solution.

Interplay between Nanoparticles and Phosphorus Dendrimers, and Their Properties.

This review presents the state of the art of interactions between two different families of nanoobjects: nanoparticles-mainly metal nanoparticles, and dendrimers-mainly phosphorhydrazone dendrimers (or dendrons). The review firstly presents the encapsulation/protection of existing nanoparticles (organic or metallic) by phosphorus-based dendrimers and dendrons. In the second part, several methods for the synthesis of metal nanoparticles, thanks to the dendrimer that acts as a template, are presented.

Personalized and Precision Medicine 2022.

This Special Issue, "Personalized and Precision Medicine 2022" (https://www [...

The Chemistry of P=N-P=X (X=S, O, NR) Linkages for the Synthesis of Dendritic Structures.

The Staudinger reaction between a phosphine and an azide, applied to phosphorus azides, has been used for the synthesis of a large variety of dendritic structures, incorporating P=N-P=X moieties (X = mainly S, but also O and N-R). Conjugation of the P=N bond with the P=X bond greatly stabilizes the P=N bond. Highly branched structures such as dendrons, dendrimers, Janus dendrimers, layered dendrimers, surface-block dendrimers, and diverse other dendritic structures incorporating such linkage have been elaborated.

Liquid-Crystalline Order in the Phosphorus-Containing DenDrimers.

The structure of phosphorus-containing dendrimers has been studied by IR spectroscopy and optical polarization microscopy. The repeating units of dendrimer molecules are mesogens. This property arises from the conjugation of the aromatic ring and the hydrazone group.

Amphiphilic phosphorous dendron micelles co-deliver microRNA inhibitor and doxorubicin for augmented triple negative breast cancer therapy.

Combined chemo/gene therapy of cancer through different action mechanisms has been emerging to enhance the therapeutic efficacy towards cancer, and still remains a challenging task due to the lack of highly effective and biocompatible nanocarriers. In this work, we report a new nanosystem based on amphiphilic phosphorus dendron (1-C12G1) micelles to co-deliver microRNA-21 inhibitor (miR-21i) and doxorubicin (DOX) for combination therapy of triple negative breast cancer. The amphiphilic phosphorus dendron bearing a long linear alkyl chain and ten protonated pyrrolidine surface groups was prepared and was demonstrated to form micelles in water solution and have a hydrodynamic size of 103.

Dendrimers, an Emerging Opportunity in Personalized Medicine?

Dendrimers are highly branched macromolecules tailorable at will to fulfil precise requirements. They have generated a great many expectations and a huge number of publications and patents in relation to medicine, including in relation to personalized medicine, but have resulted in very poor clinical translation up to now. As clinical trials are the first steps in view of developing new compounds for (a personalized) medicine, this review focusses on the clinical trials carried out with dendrimers.

Engineered Stable Bioactive Per Se Amphiphilic Phosphorus Dendron Nanomicelles as a Highly Efficient Drug Delivery System To Take Down Breast Cancer In Vivo.

Conventional small molecular chemical drugs always have challenging limitations in cancer therapy due to their high systemic toxicity and low therapeutic efficacy. Nanotechnology has been applied in drug delivery, bringing new promising potential to realize effective cancer treatment. In this context, we develop here a new nanomicellar drug delivery platform generated by amphiphilic phosphorus dendrons (1-C17G3.

In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells.

Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models.

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

Dendritic 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.

Curing inflammatory diseases using phosphorous dendrimers.

Different types of water-soluble phosphorous dendrimers have been synthesized and display many different biological properties. It has been shown in particular that phosphorous dendrimers of first generation functionalized with azabisphosphonate terminal functions are able to stimulate the human immune system ex vivo. These dendrimers are internalized by monocytes within a few seconds, and induce their anti-inflammatory activation.

Dendriplex-Impregnated Hydrogels With Programmed Release Rate.

Hydrogels 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.

Supramolecular Self-Associations of Amphiphilic Dendrons and Their Properties.

This 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.

AB Derivatives of Cyclotriphosphazene for the Synthesis of Dendrons and Their Applications.

AB compounds issued from the reactivity of hexachlorocyclotriphosphazene are relatively easy to obtain using two ways: either first the reaction of one chloride with one reagent, followed by the reaction of the five remaining Cl with another reagent, or first the reaction of five chlorides with one reagent, followed by the reaction of the single remaining Cl with another reagent. This particular property led to the use of such compounds as core for the synthesis of dendrons (dendritic wedges), using the five functions for growing the dendritic branches. The single function can be used for the synthesis of diverse types of dendrimers (onion peel, dumbbell-shape, Janus), for covalent or non-covalent grafting to solid surfaces, providing nanomaterials, for grafting a fluorophore, especially for studying biological mechanisms, or for self-associations to get micelles.

Safe Polycationic Dendrimers as Potent Oral In Vivo Inhibitors of : A New Therapy to Take Down Tuberculosis.

The long-term treatment of tuberculosis (TB) sometimes leads to nonadherence to treatment, resulting in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. Inadequate bioavailability of the drug is the main factor for therapeutic failure, which leads to the development of drug-resistant cases. Therefore, there is an urgent need to design and develop novel antimycobacterial agents minimizing the period of treatment and reducing the propagation of resistance at the same time.