Search Results (35)

Delivering of hydrophobic drugs by polymeric nanoparticles is an intensively investigated research and development field worldwide due to the insufficient solubility of many existing and potential new drugs in aqueous media. Among polymeric nanoparticles, micelles of biocompatible amphiphilic block copolymers are among the most promising candidates for solubilization, encapsulation, and delivery of hydrophobic drugs to improve the water solubility and thus the bioavailability of such drugs. In this study, amphiphilic ABA triblock copolymers containing biocompatible hydrophilic hyperbranched (dendritic) polyglycerol (HbPG) outer and hydrophobic poly(tetrahydrofuran) (PTHF) inner segments were synthesized using amine-telechelic PTHF as a macroinitiator for glycidol polymerization. These hyperbranched–linear–hyperbranched block copolymers form nanosized micelles with 15–20 nm diameter above the critical micelle concentration. Coagulation experiments proved high colloidal stability of the aqueous micellar solutions of these block copolymers against temperature changes. The applicability of block copolymers as drug delivery systems was investigated using curcumin, a highly hydrophobic, water-insoluble, natural anti-cancer agent. High and efficient drug solubilization up to more than 3 orders of magnitude to that of the water solubility of curcumin (>1500-fold) is achieved with the HbPG-PTHF-HbPG block copolymer nanomicelles, locating the drug in amorphous form in the inner PTHF core. Outstanding stability of and sustained curcumin release from the drug-loaded block copolymer micelles were observed. The in vitro bioactivity of the curcumin-loaded nanomicelles was investigated on U-87 glioblastoma cell line, and an optimal triblock copolymer composition was found, which showed highly effective cellular uptake and no toxicity. These findings indicate that the HbPG-PTHF-HbPG triblock copolymers are promising candidates for advanced drug solubilization and delivery systems. Full article

Background/Objectives: Peptide amphiphile micelles (PAMs) are an exciting nanotechnology currently being studied for a variety of biomedical applications, especially for drug delivery. Specifically, PAMs can enhance in vivo trafficking, cell-targeting, and cell interactions/internalization. However, modifying peptides, as is commonly performed to induce micellization, can influence their bioactivity. In our previous work, murine antibody responses to PAMs containing the influenza antigen M2_2–16 were slightly incongruous with prior PAM vaccine studies using other antigens. In this current work, the effect of native protein linkages and non-native micellizing moieties on M2 immunogenicity was studied. Methods: PAMs were synthesized using an elongated M2 antigen (i.e., Palm₂K-M2_1–24-(KE)₄). The PAMs were characterized, then their immunogenicity was evaluated with bone marrow-derived dendritic cells and in mice. Results: Although the modification scheme yielded immunogenic PAMs, these PAMs induced a substantial amount of off-target antibody production compared to unmodified peptidyl micelles (PMs, M2_1–24 peptide). Conclusions: While the impact PAM-induced off-target antibodies had on vaccine efficacy remains to be elucidated, on-target antibodies from both PAM- and PM-vaccinated mice were excitingly able to recognize the M2 antigen within the context of the full M2 protein. This provides preliminary evidence that the PAM-induced on-target antibodies will at minimum be able to recognize the influenza virus upon exposure. Full article

This perspective begins with an overview of the major impact that the dendron, dendrimer, and dendritic state (DDDS) discovery has made on traditional polymer science. The entire DDDS technology is underpinned by an unprecedented new polymerization strategy referred to as step-growth, amplification-controlled polymerization (SGACP). This new SGACP paradigm allows for routine polymerization of common monomers and organic materials into precise monodispersed, dendritic macromolecules (i.e., dendrons/dendrimers) with nanoscale sizes and structure-controlled features that match and rival discrete in vivo biopolymers such as proteins and nucleic acids (i.e., DNA, siRNA, mRNA, etc.). These dendritic architectures exhibit unprecedented new intrinsic properties widely recognized to define a new fourth major polymer architecture class, namely: Category (IV): dendrons, dendrimers, and random hyperbranched polymers after traditional categories: (I) linear, (II) cross-linked, and (III) simple-branched types. Historical confusion over the first examples of the structure confirmed and verified cascade, dendron, dendrimer, and arborol syntheses, while associated misuse of accepted dendritic terminology is also reviewed and clarified. The importance of classifying all dendrons and dendrimers based on branch cell symmetry and the significant role of critical nanoscale-design parameters (CNDPs) for optimizing dendritic products for pharma/nanomedicine applications with a focus on enhancing stealth, non-complement activation properties is presented. This is followed by an overview of the extraordinary growth observed for amphiphilic dendron/dendrimer syntheses and their self-assembly into dendritic supramolecular assemblies, as well as many unique applications demonstrated in pharma and nanomedicine, especially involving siRNA delivery and mRNA vaccine development. This perspective is concluded with optimistic expectations predicted for new dendron and dendrimer application roles in pharma, nanomedicine, and life sciences. Full article

Dendritic hydrogels based on carbosilane crosslinkers are promising drug delivery systems, as their amphiphilic nature improves the compatibility with poorly water-soluble drugs. In this work, we explored the impact of the complementary polymer on the amphiphilic properties of the dendritic network. Different polymers were selected as precursors, from the highly lipophilic propylene glycol (PPG) to the hydrophilic polyethylene glycol (PEG), including amphiphilic Pluronics L31, L35 and L61. The dithiol polymers reacted with carbosilane crosslinkers through UV-initiated thiol–ene coupling (TEC), and the resultant materials were classified as non-swelling networks (for PPG, PLU_L31 and PLU_L61) and high-swelling hydrogels (for PEG and PLU_L35). The hydrogels exhibited thermo-responsive properties, shrinking at higher temperatures, and exhibited an intriguing drug release pattern due to internal nanostructuring. Furthermore, we fine-tuned the dendritic crosslinker, including hydroxyl and azide pendant groups in the focal point, generating functional networks that can be modified through degradable (ester) and non-degradable (triazol) bonds. Overall, this work highlighted the crucial role of the amphiphilic balance in the design of dendritic hydrogels with thermo-responsive behavior and confirmed their potential as functional networks for biomedical applications. Full article

Cationic dendritic amphiphiles were prepared through the linkage of interesting hydrophobic molecules such as cholesterol or vitamin E to the focal point of carbosilane dendrons. These new dendritic systems self-assembled in saline, producing micellar aggregates with hydrodynamic diameters ranging from 6.5 to 9.2 nm, and critical micelle concentrations of approximately 5 and 10 μM for second- and third-generation systems, respectively. The assemblies were able to encapsulate drugs of different charges (anionic, neutral, and cationic). Surprisingly, a 92% encapsulation efficiency for diclofenac was achieved in micelles prepared from second-generation dendrons. Toxicity measurements on peripheral blood mononuclear cells indicated different behavior depending on the generation, corresponding to the micellar regime. In contrast to the third-generation system, the second-generation system was non-toxic up to 20 μM, opening a window for its use in a micellar regimen, thereby operating as a drug delivery system for different biomedical applications. Full article

Amphiphilic dendritic copolymers of arborescent poly(γ-benzyl L-glutamate) (PBG) of generations G1 and G2, grafted at their chain ends with poly(ethylene oxide) (PEO) segments (PBG-eg-PEO) were synthesized, characterized, and evaluated as nanocarriers for doxorubicin (DOX). The copolymers were designed with hydrophobic PBG cores having three different branching densities and were characterized by proton nuclear magnetic resonance (¹H NMR) spectroscopy, size exclusion chromatography (SEC), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Dynamic light scattering (DLS) measurements revealed that these amphiphilic molecules behaved like unimolecular micelles without significant aggregation in aqueous media such as phosphate-buffered saline (PBS), with diameters in the 13–29 nm range depending on the generation number and the core structure. Efficient encapsulation of DOX by these unimolecular micelles was demonstrated with drug loading capacities of up to 11.2 wt%, drug loading efficiencies of up to 67%, and pH-responsive sustained drug release, as determined by UV spectroscopy. The generation number of the copolymers and the branching density of the dendritic PBG core were found to have influenced the encapsulation and release properties of the micelles. Given the tailorable characteristics, good water dispersibility, and biocompatibility of the components used to synthesize the amphiphilic arborescent copolymers, these systems should be useful as robust nanocarriers for a broad range of therapeutic and diagnostic agents. Full article

The application of micelles as drug delivery systems has gained a great deal of attention as a means to overcome the current several drawbacks present in conventional cancer treatments. In this work, we highlight the comparison of polymeric and monomeric amphiphilic systems with a similar hydrophilic–lipophilic balance (HLB) in terms of their biocompatibility, aggregation behavior in aqueous solution, and potential in solubilizing hydrophobic compounds. The polymeric system consists of non-ionic polymeric amphiphiles synthesized via sequential RAFT polymerization of polyglycerol first-generation [G1] dendron methacrylate and cholesterol methacrylate to obtain poly(G1-polyglycerol dendron methacrylate)-block-poly(cholesterol methacrylate) (pG1MA-b-pCMA). The monomeric system is a polyglycerol second-generation [G2] dendron end-capped to a cholesterol unit. Both amphiphiles form spherical micellar aggregations in aqueous solution, with differences in size and the morphology in which hydrophobic molecules can be encapsulated. The polymeric and monomeric micelles showed a low critical micelle concentration (CMC) of 0.2 and 17 μg/mL, respectively. The results of our cytotoxicity assays showed that the polymeric system has significantly higher cell viability compared to that of the monomeric amphiphiles. The polymeric micelles were implemented as drug delivery systems by encapsulation of the hydrophobic small molecule doxorubicin, achieving a loading capacity of 4%. In summary, the results of this study reveal that using cholesterol as a building block for polymer synthesis is a promising method of preparation for efficient drug delivery systems while improving the cell viability of monomeric cholesterol. Full article

Supramolecular assembly of amphiphilic molecules in aqueous solutions to form stimuli-responsive entities is attractive for developing intelligent supramolecular materials for bioapplications. Here we report on the supramolecular chiral assembly of amphiphilic dendronized tetraphenylethylenes (TPEs) in aqueous solutions. Hydrophobic TPE moieties were connected to the hydrophilic three-fold dendritic oligoethylene glycols (OEGs) through a tripeptide proline–hydroxyproline–glycol (POG) to afford the characteristic topological structural effects of dendritic OEGs and the peptide linker. Both ethoxyl- and methoxyl-terminated dendritic OEGs were used to modulate the overall hydrophilicity of the dendronized TPEs. Their supramolecular aggregates exhibited thermoresponsive behavior that originated from the dehydration and collapse of the dendritic OEGs, and their cloud point temperatures (T_cps) were tailored by solution pH conditions. Furthermore, aggregation-induced fluorescent emission (AIE) from TPE moieties was used as an indicator to follow the assembly, which was reversibly tuned by temperature variation at different pH conditions. Supramolecular assemblies from these dendronized amphiphiles exhibited enhanced supramolecular chirality, which was dominated mainly by the interaction balance between TPE with dendritic OEG and TPE with POG moieties and was modulated through different solvation by changing solution temperature or pH conditions. More interestingly, ethoxyl-terminated dendritic OEG provided a much stronger shielding effect than its methoxyl-terminated counterpart to prevent amino groups within the peptide from protonation, even in strong acidic conditions, resulting in different responsive behavior to the solution temperature and pH conditions for these supramolecular aggregates. Full article

Octadecylazanediyl dipropionic acid (C18ADPA) is a zwitterionic amphiphile with a dendritic headgroup. C18ADPA self-assembles to lamellar networks, which encompasses water and forms a low-molecular-weight hydrogel (LMWG). In this study, we use the C18ADPA hydrogel as a drug carrier for the in vivo delivery of a copper salt for wound healing in a mouse model. A structural transition was observed based on cryo-scanning electron microscope (cryo-SEM) images after drug loading. The C18ADPA hydrogel, which had a layered structure, transformed into a self-assembled fibrillar network (SAFiN). The mechanical strength of the LMWG has always been an important issue in its applications. However, due to the structural transition, both the storage and loss moduli increased. In vivo tests showed that wound closure was faster after applying the hydrogel formulation compared with the Vaseline formulation. For the first time, we have also provided histological evidence of these effects on skin tissue. The hydrogel formulation exhibited clear advantages in regenerating tissue structure over traditional delivery formulations. Full article

Photothermal therapy directly acting on the nucleus is a potential anti-tumor treatment with higher killing efficiency. However, in practical applications, it is often difficult to achieve precise nuclear photothermal therapy because agents are difficult to accurately anchor to the nucleus. Therefore, it is urgent to develop a nanoheater that can accurately locate the nucleus. Here, we designed an amphiphilic arginine-rich dendritic peptide (RDP) with the sequence CRRK(RRCG(Fmoc))₂, and prepared a nucleus-targeting nanoplatform RDP/I by encapsulating the photothermal agent IR780 in RDP for precise photothermal therapy of the tumor nucleus. The hydrophobic group Fmoc of the dendritic peptide provides strong hydrophobic force to firmly encapsulate IR780, which improves the solubility and stability of IR780. Moreover, the arginine-rich structure facilitates cellular uptake of RDP/I and endows it with the ability to quickly anchor to the nucleus. The nucleus-targeting nanoplatform RDP/I showed efficient nuclear enrichment ability and a significant tumor inhibition effect. Full article

This study describes the synthesis of novel amphiphilic linear-dendritic block copolymers and their self-assembly in water to form supramolecular nanoreactors capable of catalyzing Suzuki-Miyaura coupling reactions under “green” conditions. The block copolymers were formed through copper(I)-catalyzed alkyne-azide cycloaddition between azide functionalized poly(benzyl ether) dendrons as the perfectly branched blocks, as well as bis-alkyne modified poly(ethylene glycol), PEG, as the linear block. A first-generation poly(benzyl ether) dendron (G1) was coupled to a bis-alkyne modified PEG with molecular mass of 5 kDa, forming an ABA copolymer (G1)₂-PEG5k-(G1)₂ (yield 62%), while a second-generation dendron (G2) was coupled to a 11 kDa bis-alkyne modified PEG to produce (G2)₂-PEG11k-(G2)₂ (yield 49%). The structural purity and low dispersity of the linear-dendritic copolymers were verified by size-exclusion chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Their self-assembly was studied by dynamic light scattering, showing that (G1)₂-PEG5k-(G1)₂ and (G2)₂-PEG11k-(G2)₂ formed single populations of micelles (17 nm and 37 nm in diameter, respectively). The triazole rings located at the boundaries between the core and the corona are efficient chelating groups for transition metals. The ability of the micelles to complex Pd was confirmed by ¹H NMR, transmission electron microscopy, and inductively coupled plasma. The catalytic activity of the supramolecular linear-dendritic/Pd complexes was tested in water by model Suzuki-Miyaura reactions in which quantitative yields were achieved within 3 h at 40 °C, while, at 17 °C, a yield of more than 70% was attained after 17 h. Full article

Natural organic matter, including humic substances (HS), comprises complex secondary structures with no defined covalent chemical bonds and stabilized by inter- and intra-molecular interactions, such as hydrogen bonding, Van der Waal’s forces, and pi-pi interactions. The latest view describes HS aggregates as a hydrogel-like structure comprised by a hydrophobic core of aromatic residues surrounded by polar and amphiphilic molecules akin a self-assembled soft material. A different view is based on the classification of this material as either mass or surface fractals. The former is intended as made by the clustering of macromolecules generating dendritic networks, while the latter have been modelled in terms of a solvent-impenetrable core surrounded by a layer of lyophilic material. This study reviews the evolution of the increasingly refined models that appeared in the literature, all capable to describing the physicochemical properties of HS. All the models are critically examined and revisited in terms of their ability to provide key information on the structural organization of HS. Understanding how the molecular association pathway influences aggregation of HS also provides a key acknowledgment of their role in the environment. Full article

Hydrogels 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. Full article

The rampant growth of zinc dendrites and severe uncontrollable reactions have largely limited the industrialization of aqueous Zn-ion batteries. Electrolyte additive engineering was found to be a facile yet effective strategy in addressing these issues; however, traditional organic small molecule additives raise additional safety and health risks and thus compromise the intrinsic advantage of aqueous batteries. In this study, we report a polyacrylonitrile-co-poly(2-acrylamido-2-methylpropanesulfonic acid) (PAN-co-PAMPS) copolymer with ionic and hydrophilicity PAMPS and non-ionic PAN, which acts as an electrolyte additive to regulate the Zn deposition in aqueous Zn-ion batteries. The hydrophilicity of PAMPS is designed to meet water solubility. Moreover, ionic PAMPS reacts with a Zn anode surface, chemically peels the surface, leaves a pre-polished anode surface, and removes heterogeneity and impurity of the metal surface. All these effects are beneficial for homogeneous zinc ion deposition and long-life battery. The PAN segments act as a water-shielding layer on a Zn anode to prevent its direct contact with H₂O. Consequently, the Zn|Zn symmetric cells with additive-containing electrolytes have a much longer life than those without additives (up to eight times) at a current density of 1 mA cm⁻² and a capacity of 1 mA h cm⁻². The assembled Zn|Cu cells and the Zn|V₂O₅ full batteries also display prominent electrochemical reversibility. The reactively acidic amphiphilic polymer provides not only an alternative strategy for the design of multi-functional electrolyte additives, but also constitutes an easy-to-operate way for advancing commercialization of aqueous zinc-storage devices. Full article

Oligoethylene glycol dendron (G2) has been used in drug delivery due to its unique dendritic structure and excellent properties. In order to investigate the effects of lipophilic chains on drug delivery, the amphiphilic hybrid compound G2-C18 is synthesized, and celastrol (CSL) is selected to prepare “core-shell” structured CSL-G2-C18 nanoparticles (NPs) via the antisolvent precipitation method. Meanwhile, CSL-G2 NPs are prepared as the control. The two NPs show similar particle sizes and polydispersity indexes, while their morphologies exhibit dramatic differences. CSL-G2 NPs are solid spherical particles, while G2-C18 NPs are vesicles. The two NPs present ideal stability and similar release tendencies. The in vitro toxicity results show that the cell inhibition effect of CSL-loaded NPs is significantly enhanced when compared with free CSL, and the antitumor effect of CSL-G2-C18 NPs is stronger than that of CSL-G2 NPs. The IC₅₀ value of CSL-G2 NPs and CSL-G2-C18 NPs is enhanced about 2.8-fold and 5-fold when compared with free CSL, respectively. The above results show that lipophilic chain-linking dendritic hybrid nanocarriers promote antitumor activity by affecting the morphology of NPs, which may aid in the selection of carrier designs. Full article