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Drug Delivery 2017Positron emission tomography (PET) imaging offers physiological and biological information through the in vivo distribution of PET agents for disease diagnosis, therapy... (Review)
Review
Positron emission tomography (PET) imaging offers physiological and biological information through the in vivo distribution of PET agents for disease diagnosis, therapy monitoring and prognosis evaluation. Due to the unique structural characteristics allowing for facile modification of targeting ligands and radionuclides, dendrimers can be served as a versatile scaffold to build up various PET imaging agents, and significant breakthroughs have been made in this field over the past decades. This review focuses on the recent advances in dendrimer-based contrast agents for PET imaging of cancer, cardiovascular and other diseases. In particular, radiolabeling strategies for different PET isotopes are described in detail. Several challenges involved in clinical translation of radiolabeled dendrimers are also discussed.
Topics: Animals; Cardiovascular Diseases; Contrast Media; Dendrimers; Humans; Neoplasms; Positron-Emission Tomography
PubMed: 29124984
DOI: 10.1080/10717544.2017.1399299 -
Acta Radiologica (Stockholm, Sweden :... Sep 2010Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over... (Review)
Review
Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed.
Topics: Albumins; Contrast Media; Dendrimers; Gadolinium; Humans; Macromolecular Substances; Magnetic Resonance Imaging; Organometallic Compounds
PubMed: 20590365
DOI: 10.3109/02841851.2010.491091 -
Proceedings of the National Academy of... May 2023Nucleic acid therapeutics are becoming an important drug modality, offering the unique opportunity to address "undruggable" targets, respond rapidly to evolving...
Nucleic acid therapeutics are becoming an important drug modality, offering the unique opportunity to address "undruggable" targets, respond rapidly to evolving pathogens, and treat diseases at the gene level for precision medicine. However, nucleic acid therapeutics have poor bioavailability and are chemolabile and enzymolabile, imposing the need for delivery vectors. Dendrimers, by virtue of their well-defined structure and cooperative multivalence, represent precision delivery systems. We synthesized and studied bola-amphiphilic dendrimers for cargo-selective and on-demand delivery of DNA and small interfering RNA (siRNA), both important nucleic acid therapeutics. Remarkably, superior performances were achieved for siRNA delivery with the second-generation dendrimer, yet for DNA delivery with the third generation. We systematically studied these dendrimers with regard to cargo binding, cellular uptake, endosomal release, and in vivo delivery. Differences in size both of the dendrimers and their nucleic acid cargos impacted the cooperative multivalent interactions for cargo binding and release, leading to cargo-adaptive and selective delivery. Moreover, both dendrimers harnessed the advantages of lipid and polymer vectors, while offering nanotechnology-based tumor targeting and redox-responsive cargo release. Notably, they allowed tumor- and cancer cell-specific delivery of siRNA and DNA therapeutics for effective treatment in different cancer models, including aggressive and metastatic malignancies, outperforming the currently available vectors. This study provides avenues to engineer tailor-made vectors for nucleic acid delivery and precision medicine.
Topics: Humans; Dendrimers; Nucleic Acids; RNA, Small Interfering; DNA; Neoplasms; RNA, Double-Stranded
PubMed: 37186846
DOI: 10.1073/pnas.2220787120 -
Biomolecules Nov 2019Human neuroscience has made remarkable progress in understanding basic aspects of functional organization; it is a renowned fact that the blood-brain barrier (BBB)... (Review)
Review
Human neuroscience has made remarkable progress in understanding basic aspects of functional organization; it is a renowned fact that the blood-brain barrier (BBB) impedes the permeation and access of most drugs to central nervous system (CNS) and that many neurological diseases remain undertreated. Therefore, a number of nanocarriers have been designed over the past few decades to deliver drugs to the brain. Among these nanomaterials, dendrimers have procured an enormous attention from scholars because of their nanoscale uniform size, ease of multi-functionalization, and available internal cavities. As hyper-branched 3D macromolecules, dendrimers can be maneuvered to transport diverse therapeutic agents, incorporating small molecules, peptides, and genes; diminishing their cytotoxicity; and improving their efficacy. Herein, the present review will give exhaustive details of extensive researches in the field of dendrimer-based vehicles to deliver drugs through the BBB in a secure and effectual manner. It is also a souvenir in commemorating Donald A. Tomalia on his 80th birthday.
Topics: Animals; Blood-Brain Barrier; Brain; Brain Diseases; Dendrimers; Drug Carriers; Drug Delivery Systems; Humans
PubMed: 31783573
DOI: 10.3390/biom9120790 -
Molecules (Basel, Switzerland) May 2022The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical... (Review)
Review
The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical three-dimensional structures with surfaces that can be modified by the attachment of various drugs, hydrophilic or hydrophobic groups, or reporter molecules. In the literature, many modified dendrimer systems with various applications have been reported, including drug and gene delivery systems, biosensors, bioimaging contrast agents, tissue engineering, and therapeutic agents. Dendrimers are used for the delivery of macromolecules, miRNAs, siRNAs, and many other various biomedical applications, and they are ideal carriers for bioactive molecules. In addition, the conjugation of dendrimers with antibodies, proteins, and peptides allows for the design of vaccines with highly specific and predictable properties, and the role of dendrimers as carrier systems for vaccine antigens is increasing. In this work, we will focus on a review of the use of dendrimers in cancer diagnostics and therapy. Dendrimer-based nanosystems for drug delivery are commonly based on polyamidoamine dendrimers (PAMAM) that can be modified with drugs and contrast agents. Moreover, dendrimers can be successfully used as conjugates that deliver several substances simultaneously. The potential to develop dendrimers with multifunctional abilities has served as an impetus for the design of new molecular platforms for medical diagnostics and therapeutics.
Topics: Contrast Media; Dendrimers; Drug Carriers; Drug Delivery Systems; Gene Transfer Techniques
PubMed: 35630713
DOI: 10.3390/molecules27103237 -
Advanced Drug Delivery Reviews Dec 2005Dendrimers have unique molecular architectures and properties that make them attractive materials for the development of nanomedicines. Key properties such as defined... (Review)
Review
Dendrimers have unique molecular architectures and properties that make them attractive materials for the development of nanomedicines. Key properties such as defined architecture and a high ratio of multivalent surface moieties to molecular volume also make these nanoscaled materials highly interesting for the development of synthetic (non-viral) vectors for therapeutic nucleic acids. Rational development of such vectors requires the link to be made between dendrimer structure and the morphology and physicochemistry of the respective nucleic acid complexes and, furthermore, to the biological performance of these systems at the cellular and systemic level. The review focuses on the current understanding of the role of dendrimers in those aspects of synthetic vector development. Dendrimer-based transfection agents have become routine tools for many molecular and cell biologists but therapeutic delivery of nucleic acids remains a challenge.
Topics: Animals; Chemical Phenomena; Chemistry, Physical; Dendrimers; Gene Expression; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans
PubMed: 16310284
DOI: 10.1016/j.addr.2005.09.017 -
Molecules (Basel, Switzerland) Sep 2015To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with... (Review)
Review
To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional "only one function" to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.
Topics: Animals; Dendrimers; Drug Carriers; Humans; Molecular Structure; Nanomedicine; Nanostructures
PubMed: 26393546
DOI: 10.3390/molecules200916987 -
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 -
ACS Infectious Diseases Apr 2024Pathogenic bacteria cause the deaths of millions of people every year. With the development of antibiotics, hundreds and thousands of people's lives have been saved.... (Review)
Review
Pathogenic bacteria cause the deaths of millions of people every year. With the development of antibiotics, hundreds and thousands of people's lives have been saved. Nevertheless, bacteria can develop resistance to antibiotics, rendering them insensitive to antibiotics over time. Peptides containing specific amino acids can be used as antibacterial agents; however, they can be easily degraded by proteases . To address these issues, branched peptide dendrimers are now being considered as good antibacterial agents due to their high efficacy, resistance to protease degradation, and low cytotoxicity. The ease with which peptide dendrimers can be synthesized and modified makes them accessible for use in various biological and nonbiological fields. That is, peptide dendrimers hold a promising future as antibacterial agents with prolonged efficacy without bacterial resistance development. Their stability and multivalence allow them to effectively target multi-drug-resistant strains and prevent biofilm formation. Thus, it is interesting to have an overview of the development and applications of peptide dendrimers in antibacterial research, including the possibility of employing machine learning approaches for the design of AMPs and dendrimers. This review summarizes the synthesis and applications of peptide dendrimers as antibacterial agents. The challenges and perspectives of using peptide dendrimers as the antibacterial agents are also discussed.
Topics: Humans; Anti-Bacterial Agents; Dendrimers; Peptides; Bacteria
PubMed: 38428037
DOI: 10.1021/acsinfecdis.3c00624 -
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