Dendrimer Architectonics to Treat Cancer and Neurodegenerative Diseases with Implications in Theranostics and Personalized Medicine
13 Jan 2021-Vol. 4, Iss: 2, pp 1115-1139
TL;DR: This review focuses on the diagnostic, therapeutic and theranostic potential of DA-based nanocarriers in treating cancer and neurodegenerative disorders like AD and Parkinson's disease (PD), among others.
Abstract: Integration of diagnostic and therapeutic functions in a single platform namely theranostics has become a cornerstone for personalized medicine. Theranostics platform facilitates noninvasive detect...
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TL;DR: In this paper, the authors encapsulated individual nanocrystals in phospholipid block-copolymer micelles and demonstrated both in vitro and in vivo imaging, and the nanocrystal-micelles acted as in vitro fluorescent probes to hybridize to specific complementary sequences.
Abstract: Fluorescent semiconductor nanocrystals (quantum dots) have the potential to revolutionize biological imaging, but their use has been limited by difficulties in obtaining nanocrystals that are biocompatible. To address this problem, we encapsulated individual nanocrystals in phospholipid block–copolymer micelles and demonstrated both in vitro and in vivo imaging. When conjugated to DNA, the nanocrystal-micelles acted as in vitro fluorescent probes to hybridize to specific complementary sequences. Moreover, when injected into Xenopus embryos, the nanocrystal-micelles were stable, nontoxic (<5 × 109 nanocrystals per cell), cell autonomous, and slow to photobleach. Nanocrystal fluorescence could be followed to the tadpole stage, allowing lineage-tracing experiments in embryogenesis.
113 citations
31 Dec 1969
TL;DR: In order to decrease the cytotoxicity of dendrimers, scientists started to introduce different chemical modifications on the periphery of the nanomolecule.
Abstract: Drug delivery systems are molecular platforms in which an active compound is packed into or loaded on a biocompatible nanoparticle. Such a solution improves the activity of the applied drug or decreases its side effects. Dendrimers are promising molecular platforms for drug delivery due to their unique properties. These macromolecules are known for their defined size, shape, and molecular weight, as well as their monodispersity, the presence of the void space, tailorable structure, internalization by cells, selectivity toward cells and intracellular components, protection of guest molecules, and controllable release of the cargo. Dendrimers were tested as carriers of various molecules and, simultaneously, their toxicity was examined using different cell lines. It was discovered that, in general, dendrimer cytotoxicity depended on the generation, the number of surface groups, and the nature of terminal moieties (anionic, neutral, or cationic). Higher cytotoxicity occurred for higher-generation dendrimers and for dendrimers with positive charges on the surface. In order to decrease the cytotoxicity of dendrimers, scientists started to introduce different chemical modifications on the periphery of the nanomolecule. Dendrimers grafted with polyethylene glycol (PEG), acetyl groups, carbohydrates, and other moieties did not affect cell viability, or did so only slightly, while still maintaining other advantageous properties. Dendrimers clearly have great potential for wide utilization as drug and gene carriers. Moreover, some dendrimers have biological properties per se, being anti-fungal, anti-bacterial, or toxic to cancer cells without affecting normal cells. Therefore, intrinsic cytotoxicity is a comprehensive problem and should be considered individually depending on the potential destination of the nanoparticle.
74 citations
TL;DR: In this paper, Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment, and current therapeutic treatments have n...
Abstract: Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have n...
18 citations
TL;DR: The safety and efficiency of essentially two main types of dendrimers, based on polylysine and polyamidoamide scaffolds, have been assessed up to now and were tested with the aim of treating mainly bacterial vaginosis, cancers, and COVID-19.
Abstract: 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. Many of these clinical trials have been recently posted (2020–2022); thus, only very few concern phase 3. The safety and efficiency of essentially two main types of dendrimers, based on polylysine and polyamidoamide scaffolds, have been assessed up to now. These dendrimers were tested with the aim of treating mainly bacterial vaginosis, cancers, and COVID-19.
17 citations
19 Jul 2021
TL;DR: This review focuses on recent progress in the development and use of aptamer-functionalized DNA nanodevices as theranostic agents, their characterization, applications as delivery platforms, and advantages, and a perspective on the challenges and possible solutions for the clinical translation of aptamers and DNA nanodesvices in the domain of cancer therapeutics.
Abstract: DNA has been demonstrated to be a versatile material for construction at the nanoscale. DNA nanodevices are highly programmable and allow functionalization with multiple entities such as imaging modalities (fluorophores), targeting entities (aptamers), drug conjugation (chemical linkers), and triggered release (photoresponsive molecules). These features enhance the use of DNA nanodevices in biological applications, catalyzing the rapid growth of this domain of research. In this review, we focus on recent progress in the development and use of aptamer-functionalized DNA nanodevices as theranostic agents, their characterization, applications as delivery platforms, and advantages. We provide a brief background on the development of aptamers and DNA nanodevices in biomedical applications, and we present specific applications of these entities in cancer diagnosis and therapeutics. We conclude with a perspective on the challenges and possible solutions for the clinical translation of aptamer-functionalized DNA nanodevices in the domain of cancer therapeutics.
15 citations
References
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TL;DR: C encapsulated individual nanocrystals in phospholipid block–copolymer micelles acted as in vitro fluorescent probes to hybridize to specific complementary sequences and were followed to the tadpole stage, allowing lineage-tracing experiments in embryogenesis.
Abstract: Fluorescent semiconductor nanocrystals (quantum dots) have the potential to revolutionize biological imaging, but their use has been limited by difficulties in obtaining nanocrystals that are biocompatible. To address this problem, we encapsulated individual nanocrystals in phospholipid block-copolymer micelles and demonstrated both in vitro and in vivo imaging. When conjugated to DNA, the nanocrystal-micelles acted as in vitro fluorescent probes to hybridize to specific complementary sequences. Moreover, when injected into Xenopus embryos, the nanocrystal-micelles were stable, nontoxic (<5 x 10(9) nanocrystals per cell), cell autonomous, and slow to photobleach. Nanocrystal fluorescence could be followed to the tadpole stage, allowing lineage-tracing experiments in embryogenesis.
3,049 citations
TL;DR: Starburst dendrimers are three-dimensional, highly ordered oligomeric and polymeric compounds formed by reiterative reaction sequences starting from smaller molecules—“initiator cores” such as ammonia or pentaerythritol.
Abstract: Starburst dendrimers are three-dimensional, highly ordered oligomeric and polymeric compounds formed by reiterative reaction sequences starting from smaller molecules—“initiator cores” such as ammonia or pentaerythritol. Protecting group strategies are crucial in these syntheses, which proceed via discrete “Aufbau” stages referred to as generations. Critical molecular design parameters (CMDPs) such as size, shape, and surface chemistry may be controlled by the reactions and synthetic building blocks used. Starburst dendrimers can mimic certain properties of micelles and liposomes and even those of biomolecules and the still more complicated, but highly organized, building blocks of biological systems. Numerous applications of these compounds are conceivable, particularly in mimicking the functions of large biomolecules as drug carriers and immunogens. This new branch of “supramolecular chemistry” should spark new developments in both organic and macromolecular chemistry.
3,022 citations
TL;DR: The A β-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk are discussed, and how to design effective strategies for AD therapy by targeting ApO-E is considered.
Abstract: Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the e4 allele are at increased risk of AD compared with those carrying the more common e3 allele, whereas the e2 allele decreases risk. Presence of the APOE e4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.
2,463 citations
TL;DR: Dendritic Fluorescent Sensors and Supramolecular Assemblies between Dendrimers and Surfactants or Polymers 1885 4.8.1.
Abstract: 3.15. Miscellaneous Photophysical Studies 1874 3.16. Dendritic Fluorescent Sensors 1875 3.17. Nonlinear Optical Properties 1875 4. Supramolecular Properties 1876 4.1. Concepts and Pioneering Studies 1876 4.2. H-Bonding 1877 4.3. Electrostatic Binding 1877 4.4. Combined H-Bonding/Ionic Bonding 1879 4.5. Coordination of Metal Ions 1880 4.6. Intradendritic π-π Interactions 1880 4.7. Encapsulation of Neutral Guest Molecules 1881 4.8. Interdendritic Supramolecular Associations 1883 4.8.1. Liquid Crystals 1883 4.8.2. Other Dendritic Self-Assemblies 1884 4.9. Supramolecular Assemblies between Dendrimers and Surfactants or Polymers 1885
1,649 citations
TL;DR: Challenges Eun-Kyung Lim,†,‡,§ Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh,*,† and Kwangyeol Lee
Abstract: Challenges Eun-Kyung Lim,†,‡,§ Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh,*,† and Kwangyeol Lee* Department of Chemistry, Korea University, Seoul 136-701, Korea †Department of Radiology, Yonsei University, Seoul 120-752, Korea Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul 120-749, Korea Division of Pathology, NSABP Foundation, Pittsburgh, Pennsylvania 15212, United States Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Korea ‡BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea Electronic Materials Laboratory, Samsung Advanced Institute of Technology, Mt. 14-1, Nongseo-Ri, Giheung-Eup, Yongin-Si, Gyeonggi-Do 449-712, Korea
998 citations