-
Molecules (Basel, Switzerland) Apr 2021With their ten peripheral substituents, pillar[5]arenes are attractive compact scaffolds for the construction of nanomaterials with a controlled number of functional... (Review)
Review
With their ten peripheral substituents, pillar[5]arenes are attractive compact scaffolds for the construction of nanomaterials with a controlled number of functional groups distributed around the macrocyclic core. This review paper is focused on the functionalization of pillar[5]arene derivatives with small dendrons to generate dendrimer-like nanomaterials and bioactive compounds. Examples include non-viral gene vectors, bioactive glycoclusters, and liquid-crystalline materials.
Topics: Calixarenes; Dendrimers; Genetic Vectors; Humans; Models, Molecular; Nanostructures; Tissue Scaffolds
PubMed: 33919656
DOI: 10.3390/molecules26082358 -
Wiley Interdisciplinary Reviews.... Mar 2022Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses... (Review)
Review
Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti-tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well-defined architecture. This review offers a comprehensive overview of dendrimer-based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune-suppressive responses (immune checkpoint inhibitors). On-going works and prospects of dendrimer-based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer-based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Topics: Dendrimers; Humans; Immunity; Immunotherapy; Nanomedicine; Nanoparticles; Neoplasms
PubMed: 34414690
DOI: 10.1002/wnan.1752 -
ACS Biomaterials Science & Engineering May 2022Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of...
Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of cationic amphiphilic dendrons with different hydrophobic alkyl chains (C) and different generations (G) and demonstrate their use for anticancer applications. The results revealed that lower-generation dendrons (G) with a longer hydrophobic alkyl chain (C and C) have stronger antitumor activity. Among these dendrons, a lead candidate C-G was identified that demonstrated excellent broad-spectrum antitumor activity in 7 cancer cell lines including highly metastatic tumor cells, while simultaneously, hemolysis was negligible. Mechanistic studies showed that C-G could lead to cytoplasmic leakage and induce cancer cell necrosis through membrane disruption. In addition, C-G showed potent inhibition of tumor growth in a B16-F10 melanoma model. In conclusion, these findings demonstrate that the cationic amphiphilic dendron might be a promising agent for anticancer application.
Topics: Cations; Dendrimers; Humans; Hydrophobic and Hydrophilic Interactions
PubMed: 35395157
DOI: 10.1021/acsbiomaterials.2c00181 -
Biomaterials Science May 2023With the alarming and prevailing antimicrobial resistance (AMR) comes an urgent need for novel antimicrobial agents that are not only effective and robust but also do... (Review)
Review
With the alarming and prevailing antimicrobial resistance (AMR) comes an urgent need for novel antimicrobial agents that are not only effective and robust but also do not induce resistance development. Amphiphilic dendrimers are emerging as a promising new paradigm to combat bacterial AMR. They can mimic antimicrobial peptides to produce potent antibacterial activity yet with a low likelihood of generating resistance. In addition, they are stable against enzymatic degradation thanks to their unique dendritic architecture. Importantly, these amphiphilic dendrimers are composed of distinct hydrophobic and hydrophilic entities bearing dendritic structures, which can be precisely designed and synthesized to optimize the hydrophobic-hydrophilic balance yielding potent antibacterial activity while minimizing adverse effects and drug resistance. In this short review, we present the challenges and current state of research in developing amphiphilic dendrimers as new antibiotic substitutes. We start with a brief overview of the advantages and opportunities associated with using amphiphilic dendrimers to combat bacterial AMR. We then outline the specific considerations and the mechanisms underlying the antibacterial activity of amphiphilic dendrimers. We focus on the importance of the amphiphilic nature of a dendrimer that balances hydrophobicity and hydrophilicity gauging the hydrophobic entity and the dendrimer generation, branching unit, terminal group and charge to allow high antibacterial potency and selectivity while minimizing toxicity. Finally, we present the future challenges and perspectives for amphiphilic dendrimers as antibacterial candidates for combating AMR.
Topics: Dendrimers; Anti-Bacterial Agents; Drug Resistance, Microbial
PubMed: 36866708
DOI: 10.1039/d2bm01878k -
Molecules (Basel, Switzerland) Nov 2022The structure of phosphorus-containing dendrimers has been studied by IR spectroscopy and optical polarization microscopy. The repeating units of dendrimer molecules are...
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. An analysis of the IR spectra showed that, with an increase in the generation number, the width of the stretching vibration bands ν(PN) and ν(PO) increases. Difficulties in packing molecules of higher generations cause conformational diversity. The shape of the dendrimer molecules was determined by analyzing the increments of dipole moments. Additionally, the modeling of the stacking of repeating links was performed. The spherical model of molecules does not satisfy the experimental dipole moments of the dendrimers. The flat disk model is more suitable for explaining step changes in dipole moments. The liquid-crystalline ordering of dendrimers under the action of applied pressure was found. With simultaneous heating and uniaxial compression, optical anisotropy appears in dendrimers. It is associated with the formation of liquid-crystalline order. However, a thermodynamically stable liquid-crystalline phase is not formed in this case. Dendrimers most likely have disk-shaped molecules.
Topics: Phosphorus; Dendrimers; Liquid Crystals; Molecular Conformation; Spectrophotometry, Infrared
PubMed: 36500305
DOI: 10.3390/molecules27238214 -
Current Drug Delivery 2022Compared to other nano polymers, dendrimers have novel three-dimensional, synthetic hyperbranched, nano-polymeric structures. These supramolecular dendritic structures... (Review)
Review
Compared to other nano polymers, dendrimers have novel three-dimensional, synthetic hyperbranched, nano-polymeric structures. These supramolecular dendritic structures have a high degree of significant surface and core functionality in the transportation of drugs for targeted therapy, specifically in host-guest response, gene transfer therapy, and imaging of biological systems. However, there are conflicting shreds of evidence regarding biological safety and dendrimers toxicity due to their positive charge at the surface. It includes cytotoxicity, hemolytic toxicity, haematological toxicity, immunogenicity, and in vivo toxicity. Surface modification of the dendrimer group is one of the methods to resolve these issues. This review aimed at investigating different strategies that can reduce toxicity and improve the biocompatibility of different dendrimers. From that viewpoint, we broaden the structural and safe characteristics of the dendrimers in the biomedical and pharmaceutical fields.
Topics: Dendrimers; Diagnostic Imaging; Polymers
PubMed: 34674620
DOI: 10.2174/1567201818666211021160441 -
Current Medicinal Chemistry 2022Drug delivery systems are designed for the targeted delivery and controlled release of medicinal agents. Among the materials employed as drug delivery systems,... (Review)
Review
Drug delivery systems are designed for the targeted delivery and controlled release of medicinal agents. Among the materials employed as drug delivery systems, dendrimers have gained increasing interest in recent years because of their properties and structural characteristics. The use of dendrimer-nanocarrier formulations enhances the safety and bioavailability, increases the solubility in water, improves stability and pharmacokinetic profile, and enables efficient delivery of the target drug to a specific site. However, the synthesis of dendritic architectures through convergent or divergent methods has drawbacks and limitations that disrupt aspects related to design and construction, and consequently, slow down the transfer from academia to industry. In that sense, the implementation of click chemistry has received increasing attention in the last years, as it offers new efficient approaches to obtain dendritic species in good yields and higher monodispersity. This review focuses on recent strategies for building dendrimer drug delivery systems using click reactions from 2015 to early 2021. The dendritic structures showed in this review are based on β -cyclodextrins (β-CD), poly(amidoamine) (PAMAM), dendritic poly (lysine) (PLLD), dimethylolpropionic acid (bis-MPA), phosphoramidate (PAD), and poly(propargyl alcohol-4-mercaptobutyric (PPMA).
Topics: Click Chemistry; Dendrimers; Drug Compounding; Drug Delivery Systems; Humans; Solubility
PubMed: 34711155
DOI: 10.2174/0929867328666211027124724 -
Macromolecular Rapid Communications Mar 2019Multicomponent miktoarm stars (MMSs) comprising at least three kinds of chemically different arm segments are extremely important due to their great potential as... (Review)
Review
Multicomponent miktoarm stars (MMSs) comprising at least three kinds of chemically different arm segments are extremely important due to their great potential as multiphase materials to elucidate composition/topology-dependent properties and applications. At present, a "core first" route gives ABC stars, "coupling onto" and combinatorial methods afford ABC and ABCD stars, and modular and iterative approaches enable facile synthesis of MMSs with five or more components. Meanwhile, the introduction of stimuli-labile linkages and couplable groups into star polymers further enriches the family of smart materials. Upon external stimuli, linking reaction, or postpolymerization modification, miktoarm stars are potentially converted into other architectural polymers such as linear, tadpole-like, graft, and dendrimer-like polymers via cleavage and rearrangement in the chain structure. This feature article aims to systematically summarize the synthetic methods and versatile topological transitions of ABC, ABCD, and ABCDE stars. The advantages and limitations of each approach are highlighted, and the future considerations on developments and challenges are discussed.
Topics: Dendrimers; Molecular Structure; Polymerization; Polymers
PubMed: 30480853
DOI: 10.1002/marc.201800571 -
Journal of Colloid and Interface Science Jan 2022Hierarchical dendrimer-based polyion complex (PIC) vesicles with multiple compartments have attracted considerable attention as functional delivery vehicles and...
Hierarchical dendrimer-based polyion complex (PIC) vesicles with multiple compartments have attracted considerable attention as functional delivery vehicles and nano-carriers. Formation of these vesicles relies on the electrostatic assembly of asymmetric polyelectrolytes, namely branched dendrimers with linear polyion-neutral diblock copolymers. However, successful incorporation of dendrimers in vesicle lamellae is challenging due to the compact structure of dendrimers, and therefore, vesicles reported so far are prepared mainly with low generation dendrimers which lack the cavity required for carrier functions. Here, we present a new assembly combination of amine-terminated dendrimer polyamidoamine (PAMAM) with polyion-neutral diblock copolymer poly (styrene sulphonate-b-ethylene oxide) (PSS-b-PEO). The strong charge interaction between the building blocks leads to stable and well-defined PIC vesicles that can tolerate not only different PSS block lengths but, more importantly, also different dendrimer generations from 2 to 7. As a consequence, high generation dendrimers with a cavity can be packed in the vesicle wall, and one obtains hierarchical PIC vesicles with multiple compartments, namely the dendrimer cavity for loading small hydrophobic cargo, and the vesicle lumen for encapsulating hydrophilic macromolecules. Our study demonstrates that combining proper building blocks enables to manipulate the charge interactions, which is essential for controlling the dendrimer packing and the formation of PIC vesicles. These findings should be helpful for understanding the assembly of asymmetric (linear / branched) polyelectrolyte complexes, as well as for designing new hierarchical PIC vesicles for controlled delivery of multiple active substances.
Topics: Dendrimers; Ions; Polyamines
PubMed: 34390996
DOI: 10.1016/j.jcis.2021.07.140 -
Journal of Controlled Release :... Jun 2022Dendrimers have been comprehensively used for cargo delivery, nucleic acid delivery (genes, miRNA/siRNAs), delivery of macromolecules, and other various biomedical... (Review)
Review
Dendrimers have been comprehensively used for cargo delivery, nucleic acid delivery (genes, miRNA/siRNAs), delivery of macromolecules, and other various biomedical applications. Dendrimers are highly versatile in function and can be engineered as multifunctional biomacromolecules by modifying the surface for fulfilling different applications. Dendrimers are being used for crosslinking of existing synthetic and natural polymeric scaffolds to regulate their binding efficiency, stiffness, biocompatibility, transfection, and many other properties to mimic the in vivo extracellular matrix in tissue engineering and regenerative medicine (TERM). Dendritic inter-cellular linkers can enhance the linkages between cells and result in scaffold-independent tissue constructs. Effectively engineered dendrimers are the ideal molecules for delivering bioactive molecules such as cytokines, chemokines, growth factors, etc., and other metabolites for efficaciously regulating cell behavior. Dendrimeric nanostructures have shown tremendous results in various TERM fields like stem cells survival, osteogenesis, increased crosslinking for eye and corneal repair, and proliferation in cartilage. This review highlights the role and various aspects of dendritic polymers for TERM in general and with respect to specific tissues. This review also covers novel explorations and insights into the use of dendrimers in TERM, focusing on the developments in the past decade and perspective of the future.
Topics: Dendrimers; Nanostructures; Polymers; Regenerative Medicine; Tissue Engineering
PubMed: 35452764
DOI: 10.1016/j.jconrel.2022.04.008