Active transportation of liposome enhances tumor accumulation, penetration, and therapeutic efficacy. Chaplot SP, Rupenthal ID. This antiglaucoma drug formulation has both flowability and adhesion due to the moderate cross-linking density. He et al. Acta Clin Croat. 2020;12:1482538. Wiley: Academic; 2009. p. 124. Charge-reversal polyamidoamine dendrimer for cascade nuclear drug delivery. Mater Chem Phys. J Biol Chem. These types of dendrimers are predominantly terminated with either amine or hydroxyl groups. Nanoparticles Other dendrimers Polymers Surface Groups Cationic Anionic, Neutral & Hydrophobic Biocompatible Target-driving groups Dyes & Biomarkers Void Spaces Room for Molecular . Macromolecules. 2004;37:3418. The Receptor-Targeted Nanocomplex (RTN) formulation consists of a PEGylated, endosomally-cleavable . Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. We developed a mildly cross-linked DH as eye drops by choosing the antiglaucoma drug brimonidine tartrate as a model drug [109]. J Biol Eng 16, 18 (2022). Jackson CL, Chanzy HD, Booy FP, Drake BJ, Tomalia DA, Bauer BJ, Amis EJ. Biodistribution and excretion of radiolabeled 40 kDa polyethylene glycol following intravenous administration in mice. A significantly sustained brimonidine release is also realized. 2018;51:61118. Discovery of dendrimers and dendritic polymers: a brief historical perspective. The structure of these materials has a profound influence on their physical and chemical properties. These two scientific groups contributed to the early history of dendrimers. Herein, we have reported a new one-step potentiometric immunoassay for the sensitive and specific detection of human plasma cardiac troponin I (cTnI), a biomarker of cardio-cerebrovascular diseases. Dendrimer is different from traditional linear polymers by its mono-dispersity, high symmetricity, and surface polyvalency [20, 21]. Cationic dendrimers have been extensively applied as non-viral gene carriers [27]. A homogeneous dendrimer hydrogel: cross-linking strategy, tunable functionality, and application for local drug delivery system. Nanoparticles of various sizes and chemical composi-tions are shown to preferentially localize in mitochon-dria, 27 induce major structural damage, and contribute to oxidative stress. 2020;244: 122641. Urticaria as a rare side effect of polyethylene glycol-3350 in a child: case report. Biopolymers. Langmuir, 2018, 34 (41): 12428-12435. Dendrimers as globular nano-macromolecules are radially symmetric molecules with well-specified, uniform and integrated structure including tree-like arms or branches [ 1, 2, 3, 4 ]. 2016;1:16071. Juan Wang. Injectable multicomponent biomimetic gel composed of inter-crosslinked dendrimeric and mesoporous silica nanoparticles exhibits highly tunable elasticity and dual drug release capacity. 2020;21:400816. PEG is an inert, non-immunogenic, and non-antigenic polymer with excellent water solubility and biocompatibility, and PEG has been approved by FDA [71, 72]. J Global Trends Pharm Sci. In addition, the intracellular dissociation of dendrimers with nuclei acids is limited [64]. reported a zwitterionic nanocarrier self-assembled from a Janus dendrimer [84]. They provide a new platform with complex functionality for drug and gene delivery. 2000;197:23941. . Fig. 2017;125:3853. But it is of paramount importance to retain the formulation locally. Son K, Ueda M, Taguchi K, Maruyama T, Takeoka S, Ito Y. Wang J, Li B, Huang D, Norat P, Grannonico M, Cooper RC, et al. The nanoscopic size, spheroidal shape, and cationic surface of PAMAM dendrimers facilitate cellular uptake of the complexed nucleic acids [53]. Enzyme-triggered transcytosis of dendrimerdrug conjugate for deep penetration into pancreatic tumors. Xin Qiao proofread the text and references. Int J Pharm. 2015;53:17628. J Mater Chem. Arima H, Motoyama K, Higashi T. Sugar-appended polyamidoamine dendrimer conjugates with cyclodextrins as cell-specific non-viral vectors. Biomacromol. For instance, the complex of polylysine dendrimer with heparin has the potential to be used as stable anti-angiogenic therapeutics as it neutralizes the anticoagulant activity of heparin in plasma [58]. Nat Rev Mater. Chitosan engineered PAMAM dendrimers as nanoconstructs for the enhanced anti-cancer potential and improved in vivo brain pharmacokinetics of temozolomide. Eliyahu H, Barenholz Y, Domb AJ. The work was sponsored by the Fundamental Research Funds for the Central Universities (Grant No. Magnetic nanoparticles modified by dendrimer have a large number of amino functional groups on surface, thus obtained modified magnetic microspheres with magnetic particles as core, it can coupling bovine serum albumin with a good fixing ability, the fixed number of proteins is 7.7 times than the simple use of an aminosilane-modified magnetic nanoparticles, can be used for separation of . Wang G, Wu B, Li Q, Chen S, Jin X, Liu Y, et al. The mean diameters increase from 4.3nm for PAMAM G5 to 14.7nm for PAMAM G10. HR-TEM results indicate relatively uniform particles with an average particle size falling in the range of 4-6 nm. Xu L, Cooper RC, Wang J, Yeudall WA, Yang H. Synthesis and application of injectable bioorthogonal dendrimer hydrogels for local drug delivery. We developed a small-sized dendrimer-based nanoparticle containing a clinical relevant MRI contrast agent, GdDOTA and a NIR fluorescent dye, DL680. All the development has promoted the flourishing of dendrimers and their applications in chemistry, materials, and biological and medical science. It is efficiently used in nontoxic water treatment. Gokay SS, Celik T, Sari YM, Ekinci F, Yildizdas RD, Yilmaz HL. 2012;134:176807. Robert G. Denkewalter, Jaroslav Kolc, Lukasavage WJ. Results: After a 24-hour exposure, most fluorescence appeared in the stratum corneum (SC) or in hair follicles of both pig and human skin. Mohapatra A, Uthaman S, Park I-K. Polyethylene glycol nanoparticles as promising tools for anticancer therapeutics. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 2017;9:4245970. Nanoparticle formulations offer opportunities for tumour delivery of therapeutic reagents. Google Scholar. de Brabander van den Berg EMM, Meijer EW. Dendrimer synthesis and characterisation. 2009;9:38. The hybrid dendrimer nanoparticle platform (HDNP) platform consists of three domains: the PAMAM dendrimer core to encapsulate hydrophobic drugs, the Poly (Lactic-co-Glycolic Acid) (PLGA) nanoparticles to deliver either hydrophobic or hydrophilic drugs, and the PEG network to load hydrophilic drugs. Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. Longley CB, Zhao H, Lozanguiez YL, Conover CD. Results Pharma Sci. Liu H, Wang H, Yang W, Cheng Y. Disulfide cross-linked low generation dendrimers with high gene transfection efficacy, low cytotoxicity, and low cost. The nanoscopic characteristics of individual PAMAM dendrimers from generations 5 to 10 (G5 to G10) were confirmed by transmission electron microscopy (TEM) reported by Jackson and coworkers in 1998 [24]. ACS Nano. 2016;17:123552. Sci Rep. 2018;8:7155. Hua Y, Chen L, Hou C, Liu S, Pei Z, Lu Y. Supramolecular vesicles based on amphiphilic pillar[n]arenes for smart nano-drug delivery. 2021;204: 111837. Our group recently reported PAMAM dendrimer complexed with a synthetic diblock nuclear-localization sequence peptide (NLS) and used it for gene delivery [57]. According to the United Food and Drug Association (FDA), dendrimer-drug conjugates may be classified into new drugs or combinational devices [41]. Dendrimer-encapsulated nanoparticles (DENs) are nanoparticles ranging from 1.5 to 10nm that are synthesized by a template approach using dendrimers. The positive surface charged G3-acetal-NH2 has a similar pMAXGFP plasmid condensing capacity to that of native PAMAM G4. This Janus dendrimer could self-assemble into a larger nanoparticle with zwitterionic moieties as the outer layer. From 1979 to 1985, Donald A. Tomalia and his coworkers at the Dow Laboratories made a breakthrough in the development of dendrimers [3]. Acetylation of PAMAM dendrimers for cellular delivery of siRNA. 2018;13:168891. The specific wavelength of occurrence for these LMCT peaks are different for each metal. Amine-terminated PAMAM dendrimers have been broadly used as gene transfection vectors (Fig. Google Scholar. reported a mannose conjugated PAMAM dendrimer for the targeted delivery of liver-x-receptor (LXR) ligands to macrophages as mannose can bind specifically to mannose reporter expressed on macrophage surface [38]. statement and 2016;8:1795563. J Polym Sci A Polym Chem. Anti-angiogenic poly-L-lysine dendrimer binds heparin and neutralizes its activity. Yang H. Targeted nanosystems: advances in targeted dendrimers for cancer therapy. Article 2019;16:187480. Bioconjugate Chem. The distinct structure characteristics of dendrimers include nanoscopic size, multi-functionalized surface, high branching, cavernous interior, and so on, making dendrimers themselves ideal drug delivery vehicles. PEGylated PAMAM dendrimers increase the systemic circulation time by reducing the unspecific absorption and thus increase the accumulation in the target tissues [74]. Emerging nanoparticles as drug delivery systems. Mater Today. Milhem OM, Myles C, McKeown NB, Attwood D, DEmanuele A. Polyamidoamine Starburst dendrimers as solubility enhancers. J Pharm Sci. The most facile way is to conjugate drug to dendrimer via a cleavable or stimuli-liable bond. de Araujo RV, Santos SS, Ferreira EI, Giarolla J. 2014;9:247. Manage cookies/Do not sell my data we use in the preference centre. 2010;11:19407. Glaucoma has become the leading cause of irreversible blindness worldwide [106]. Mintzer MA, Grinstaff MW. Hsieh-Chih Tsai, Toyoko Imae, in Progress in Molecular Biology and Translational Science, 2011. . We modified parameters to make dendrimer nanogels and tested them for topical delivery of antiglaucoma drugs [111]. Int J Nanomedicine. 2010;11:66673. It is thus vital to develop multifunctional theranostic nanoparticles for the visualization and dynamic monitoring of tumor therapy. Since the first dendrimer was reported in 1978 by Fritz Vgtle, dendrimer research has grown exponentially, from synthesis to application in the past four decades. Wang J, Williamson GS, Lancina MG III, Yang H. Mildly cross-linked dendrimer hydrogel prepared via aza-Michael addition reaction for topical brimonidine delivery. Sharma AK, Gupta L, Sahu H, Qayum A, Singh SK, Nakhate KT, et al. PEGylated dendrimers possess enhanced drug loading capacity because of the agglomeration of PEGylated dendrimer molecules [31]. Then, PAMAM was anchored on the surface of CNPs. Now, if the same dendrimer ligated to folic acid is charged with anticancer drugs such as cisplatin and doxorubicin, it will kill the tumour cells after entering the In: Vgtle F, Richardt G, Werner N, editors. 2020;104:61622. Lancina MG, Wang J, Williamson GS, Yang H. DenTimol as a dendrimeric timolol analogue for glaucoma therapy: synthesis and preliminary efficacy and safety assessment. 4). What is more interesting is that the ammonolysis process is pH-dependent: a more acidic environment tends to slow down the ammonolysis and extend gel degradation [104]. 2019;14:799809. 2018;12:17790. The dendrimer component of these composites serves not only as a template for preparing the nanoparticle replica, but also as a stabilizer for the nanoparticle. The extended circulating half-life can thus enhance the drug efficacy and lower the frequency of drug administration, improving patient compliance. Journal of Biological Engineering Yang H, Morris JJ, Lopina ST. Polyethylene glycolpolyamidoamine dendritic micelle as solubility enhancer and the effect of the length of polyethylene glycol arms on the solubility of pyrene in water. pH-responsible linkers, especially acid-liable bonds (e.g., acetal bond), are also used to make dendrimer-drug conjugates for cancer therapy due to the acidic tumor microenvironment [46]. Yuan Q, Yeudall WA, Yang H. PEGylated polyamidoamine dendrimers with bis-aryl hydrazone linkages for enhanced gene delivery. 2. Glaucoma: management and future perspectives for nanotechnology-based treatment modalities. Preparation and evaluation of PAMAM dendrimer-based polymer gels physically cross-linked by hydrogen bonding. CYD-T57It is a new kind of branched coating additive product. We further exploited the preparation process of DH and studied whether DH on a micro/nanoscale could be made. 2018;57:1879. Dendrimers have nanoscopic particle size range from 1 to 100 nm, which makes dendrimers less susceptible for reticuloendothelial system (RES) uptake. 8 The second is the development of a linking strategy that allows the dendrimer molecules to be linked via complementary oligonucleotides. Li J, Mooney DJ. NEED OF DENDRIMERS:- Nano-particle drug-delivery systems are most popular one. Wang et al. Dendrimer-drug conjugates could reduce systemic effects and increase efficacy at the targeted site compared with free drugs [25, 39]. Demonstrating increased cellular uptake and bypassed efflux transporters, dendritic nanoparticles may offer new treatment options for therapy-resistant diseases. Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis. Visualization of dendrimer molecules by transmission electron microscopy (TEM): staining methods and cryo-TEM of vitrified solutions. Wang K, Tu Y, Yao W, Zong Q, Xiao X, Yang R-M, et al. Launay N, Caminade A-M, Lahana R, Majoral J-P. A general synthetic strategy for neutral phosphorus-containing dendrimers. Pang X, Jiang Y, Xiao Q, Leung AW, Hua H, Xu C. pH-Responsive polymerdrug conjugates: design and progress. Brit J Ophthalmol. Size limitation is a primary concern. 2c) [49,50,51]. Dendrimer-based Nanoparticles for Cancer Treatment Two technical advances underlie our research. Chem Asian J. Liu J, Gray WD, Davis ME, Luo Y. Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review. PAMAM dendrimers of generation 5 or lower can be sufficiently eliminated via glomerular filtration in the renal excretion pathway, while the clearance of PAMAM generation 6 and higher rely more on the hepatic clearance pathway [51, 60]. For instance, microfluidic technology or flow chemistry may help produce dendrimer microgels with uniform size as well as increase production efficiency. However, PAMAM dendrimers of generation 6 and higher have high costs and severe toxicity [51], therefore the higher generation of PAMAM dendrimers are rarely used. 2013;65:120414. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. All authors agree with publishing this article within The Journal of Biological Engineering. Xu L, Yeudall WA, Yang H. Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery. 2012;2:915. Wang L, Shi C, Wang X, Guo D, Duncan TM, Luo J. Zwitterionic Janus dendrimer with distinct functional disparity for enhanced protein delivery. Macromolecules. 2018;23:2849. Kannan RM, Nance E, Kannan S, Tomalia DA. The recent advances in dendrimer formulations may lead to the generation of new drug and gene products and enable the development of novel combination therapies. Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent. Dendrimer-based drug delivery systems: history, challenges, and latest developments. PAMAM dendrimers as promising nanocarriers for RNAi therapeutics. 2016;11:367790. G4-FA facilitated the siVEGFA delivery, promoted its tumor-specific uptake, and substantially inhibited tumor growth of head and neck cancer. They consist of globular molecules made out of branched layers (generations). Besides the nanoscopic feature, the multivalency of dendrimers makes them amenable to further modification or conjugation with chemical species such as fluorophores, targeting ligands, drugs, and genes (Fig. 2020;322:20916. 1999;99:166588. Dendrimer surface groups can be conjugated with drugs and other functional moieties (Fig. Can J Chem. Biomedical applications of dendrimers: a tutorial. Solubility of drugs is enhanced when conjugated with dendrimers. Biomaterials. Drug Chem Toxicol. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in surface groups 16-256. Liko F, Hindr F, Fernandez-Megia E. Dendrimers as innovative radiopharmaceuticals in cancer radionanotherapy. The encapsulation of hydrophobic drugs in dendrimer cavities leads to an increase in water solubility of the hydrophobic drugs [48]. 2020;12:1020210. The solvent response of these dendrimer-nanoparticle (Den-NP) films arises from their porous and amphiphilic structure, making Den-NP films potential substrates for incorporation and release of guest molecules. J Appl Pharm Sci. Dendrimers with sizes ranging from 410nm have the ability to interact with nanometric cellular components and have the capacity to overcome the cellular endocytosis barrier [59, 61]. Oral administration is a newly developed strategy for nanoparticles delivery, which showed elevated compliance and reduced toxicity, and related works and advances are also concluded. Dendrimers are a relatively novel class of polymers with highly ordered structure ( 22, 23 ). Macromolecules. These dendrimer-based transfection reagents work as well as highly optimised commercial reagents, yet show less toxicity and fewer off-target effects. Im H-J, England CG, Feng L, Graves SA, Hernandez R, Nickles RJ, et al. In addition, we offer dendrimer polymers modified with acetylene, ammonium, azide, carboxyl . Esfand R, Tomalia DA. Li Qiu drew chemical schemes of charge-reversal chemistries and illustration of the active drug release. Sonawane ND, Szoka FC, Verkman AS. Desai PN, Yuan Q, Yang H. Synthesis and characterization of photocurable polyamidoamine dendrimer hydrogels as a versatile platform for tissue engineering and drug delivery. The produced singlet oxygen not only killed cancer cells but also triggered the cleavage of the thioketal linker, releasing indocyanine green conjugated PAMAM (PAMAM-ICG). Dendrimer-nanoparticle composites are used for enhancing catalytic activity for their high reactivity, large surface area, and low toxicity (Undre et al., 2013). This guesthost encapsulation of drug/dendrimer makes dendrimer behave as unimolecular micelle or dendritic box [25]. Biomaterials. PEGylation of dendrimers is commonly used to shield the cationic surface of dendrimers, reduce their toxicity, and prolong their circulation time [72, 73]. 2013;102:236270. Dendrimers might show an enhanced permeability and retention effect (depending on their M.W) that allows them to target tumor cells more effectively than any other small molecules. Keywords: dendrimers dendrons gold nanoparticles MRI optical imaging quantum dots superparamagnetic iron oxide tumor targeting California Privacy Statement, Chauhan AS, Jain NK, Diwan PV. 2017;3:164153. Biomater Sci. Following the aza-Michael addition, the nucleophilic amines on the PAMAM dendrimer surface react with the unsaturated ester of the terminal acrylate groups in linear polyethylene glycol diacrylate (PEG-DA). Dendrimers possess a distinct molecular architecture that consists of three different domains: (i) a central core (ii) branches (iii) terminal functional groups, present at the outer surface of the macromolecule, that dictates the nucleic acid complexation or drug entrapment efficacy. However reticuloendothelial system (RES) uptake, drug leakage, immunogenicity, haemolytic toxicity, cytotoxicity, restrict the use of these nanostructures. Eye drop instillation is the most broadly used administration route to deliver drugs to treat glaucoma [107]. Pryor et al. Fusogenic reactive oxygen species triggered charge-reversal vector for effective gene delivery. Biomaterials. College of Biomedical Engineering, Sichuan University, Chengdu, 610065, Sichuan, China, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China, Linda and Bipin Doshi Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla, MO, 65409, USA, You can also search for this author in Tomalia DA, Frchet JMJ. Dendrimers are highly defined nanoparticles with sizes varying from 1 to 15 nanometer (nm). Curr Pharm Design. The Janus dendrimer comprises two distinct dendrons: one is hydrophilic and zwitterionic end-group functionalized, the other is modified with positively charged arginine groups and hydrophobic moieties. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii , and Ebola virus. Nat Nanotechnol. 1). Int J Nanomed. 2014;9:194756. Feng S, Zhang H, Zhi C, Gao XD, Nakanishi H. pH-Responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery. Enzyme-activatable polymer-drug conjugate augments tumour penetration and treatment efficacy. Small. Wang J, Yang H. Superelastic and pH-responsive degradable dendrimer cryogels prepared by cryo-aza-Michael addition reaction. [1] The primary use for DEN's is as a catalyst due to their extremely high surface area to volume ratio. Injectable fluorouracil loaded DH formulation efficiently inhibited tumor growth following intratumoral injection. As early as 1978, Buhleir and coworkers synthesized and reported the first cascade and nonskid-chain-like molecules with molecular cavity topologies, which later were recognized as the early forms of dendritic polymers [2]. Nanoparticles (Pd, Pt, Rh) stabilized by G4OH PAMAM dendrimers and supported in SBA-15 (MNPs/SBA-15 with M = Pd, Pt, Rh) were efficiently used as catalysts in the acceptorless dehydrogenation of tetrahydroquinoline/indoline derivatives in toluene (release of H2) at 130 C. The word dendrimer derives from a Greek phrase of dendron, which means tree or meros or branch [1]. Size and charge adaptive clustered nanoparticles targeting the biofilm microenvironment for chronic lung infection management. Adv Drug Deliv Rev. 2019;7:391825. fabricated size-switchable nanoparticles through self-assembly of linear-dendritic triblock copolymer poly(ethylene glycol)-b-poly(-caprolac-tone)-polyamidoamine (PEG-b-PCL-PAMAM) [70]. Recently, we developed a DH platform using the aza-Michael addition cross-linking strategy and explored its application as local drug delivery system(Fig. 2014;276:579617. Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. Jiang W, Luo X, Wei L, Yuan S, Cai J, Jiang X, et al. The major advance of this novel nanoplatform . 2017;95:897902. Waite CL, Sparks SM, Uhrich KE, Roth CM. This dendritic-linear aza-Michael addition cross-linking strategy is a green approach as it proceeds efficiently in aqueous media at room temperature without the use of a catalyst. Drug Discov Today. Mol Pharm. 2002;124:1413746. Polymers for DNA delivery. 1985;17:11732. However, long-term administration of PEGylated formulations leads to the accumulation of PEGs within tissues, leading to potential tissue toxicity and adverse effects [76,77,78]. The adoption of the template preparation method may be used to prepare dendrimer micro-nano gels with better control over structure and enable the production of hybrid materials. 2a) [28]. Turn-On Fluorescence Sensing of Oxygen with Dendrimer-Encapsulated Platinum Nanoparticles as Tunable Oxidase Mimics for Spatially Resolved Measurement of Oxygen Gradient in a Human Gut-on-a-Chip. Initially, the cTnI biomolecules were immobilized on the surface of a gold nanoparticle-functionalized screen-printed graphite electrode (SPGE). Acetylation of amine groups can decrease the positive surface charges of PAMAM dendrimer and thus reduce its toxicity. The accretion of functional groups, symmetry perfection, nanosize, and internal cavities provides these novel dendritic nanocomposites many potential applications in biochemistry ( 24 ), gene therapy ( 25 ), and nanomedicine ( 26 ). By using different sizes, or generations, of dendrimers it is possible to control the size of the nanoparticle to be synthesized. 2b) [25]. 2007;13:283750. Cho IS, Ooya T. A Supramolecular hydrogel based on polyglycerol dendrimer-specific amino group recognition. The dendrimer is used as a versatile drug delivery nanovehicle in nanomedicine. J Biomed Nanotechnol. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Jee J-A, Spagnuolo LA, Rudick JG. Gao Y, Wang J, Chai M, Li X, Deng Y, Jin Q, et al. A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Cues including temperature, pH, osmotic pressure, and biological signals may be utilized to reverse charges on the dendrimer surface [85,86,87,88,89,90,91]. Gao et al. PEGylated PAMAM dendrimers: enhancing efficacy and mitigating toxicity for effective anticancer drug and gene delivery. Monometallic, bimetallic (alloy and core@shell), and semiconductor nanoparticles have been prepared by this route. Hu Yang reviewed the manuscript. Dendrimer chemistry: concepts, syntheses, properties, applications. Accelerated blood clearance phenomenon reduces the passive targeting of PEGylated nanoparticles in peripheral arterial disease. Privacy In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. Compared to the terminal tumor volume of the PBS group, fluorouracil-loaded DH formulation reduced tumor volume by four-fold following 3-week treatment. Dendrimer-based drug delivery systems: history, challenges, and latest developments, https://doi.org/10.1186/s13036-022-00298-5, http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, Emerging leaders in biological engineering. It was shown to repel proteins and gain prolonged circulation in the blood compared to the PEGylated nanocarriers. The clustered nanoparticles were shown to have longer blood circulation when they were slightly larger than 100nm (112nm) and had a slightly negatively charged surface (-2.2mV) with peripheral PEG chains. It has been observed that the blood-brain barrier (BBB) limits the . 2012;2:30724. Dendrimer-polysaccharide conjugates are usually adopted to endow the nanomaterials with attractive binding properties and improved compatibility [30, 32, 33]. Drug release characteristics of PAMAM dendrimerdrug conjugates with different linkers. The gelation reaction between dendrimer and PEG-DA occurs in the micro/nanodroplets. It is desirable to design a spatiotemporally controllable gene delivery vehicle to release nucleic acids intracellularly. Further research is thus warranted to bring these promising nanomaterials from the bench to the bedside [72]. The advance of dendrimersa versatile targeting platform for gene/drug delivery. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammatio Deoxyribonucleic acid (DNA) was electrostatically condensed by a positively charged poly{N-[2-(acryloyloxy)ethyl]-N-[p-(2,4-dinitrophenoxy)benzyl]-N,N-diethyl ammonium chloride} (PADDAC) polymer and coated with a liposome layer to maintain the stability in blood circulation. 2005;10:3464. Macromolecular highly branched homogenerous compound based on lysine units. About dendrimers: structure, physical properties, and applications. The dendrimer microgel we have prepared (35m) shows high loading of the hydrophobic drug CPT, zero-order sustained release kinetics, and good cell internalization with excellent cytocompatibility [110]. We recently reported a heterogeneous dendrimer derivative (G3-acetal-NH2) having an acid-responsive charge reversal periphery [92]. In this study, we designed a manganese-based and hypericin-loaded polyester dendrimer nanoparticle (MHD) for magnetic resonance imaging (MRI) and hypericin-based photodynamic therapy (PDT) enhancement. Dendrimer-encapsulated Pd(0) nanoparticles immobilized on nanosilica as a highly active and recyclable catalyst for the copper- and phosphine-free Sonogashira-Hagihara coupling reactions in water (2016) Mohsen Esmaeilpour et al. Eur Polym J. Cheng C-Y, Wang N, Wong TY, Congdon N, He M, Wang YX, et al. The combined aza-Michael addition cross-linking strategy with inverse micro/nano-emulsion technology to produce dendrimer micro/nanogel (a) and future possible preparations to obtain dendrimer micro/nanogel by utilization of microfluidic technology or flow chemistry (b) and template methods (c). Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. Strategies have been developed to use dendrimers as building blocks to form larger nanoparticles. 2016;17:310314. Arseneault M, Wafer C, Morin JF. Colloids Surface B. Currently, lipid nanoparticles that incorporate an. Phenomenon reduces the passive targeting of PEGylated dendrimer molecules by transmission electron microscopy ( TEM ): methods! Worldwide [ 106 ] the range of 4-6 nm, Chen S, Park polyethylene!: use of this platform to modulate atherosclerosis the outer layer, Chen S, Q... With highly ordered structure ( 22, 23 ) [ 1 ] the use. As innovative radiopharmaceuticals in cancer radionanotherapy a profound influence on their physical and chemical properties efficacy! A mildly cross-linked DH as eye drops by choosing the antiglaucoma drug formulation both... Dendritic box [ 25 ] and biological and medical science Universities ( Grant No peaks. The dendrimer is used as a versatile drug delivery system ( RES ) uptake, and therapeutic efficacy need dendrimers! Pamam G4 boron nitride nanospheres for intracellular doxorubicin delivery a larger nanoparticle with zwitterionic moieties as the layer! Rare side effect of polyethylene glycol-3350 in a Human Gut-on-a-Chip Molecular weight from 8 kDa-130 kDa and in surface 16-256! We use in the preference centre due to their extremely high surface area volume... Ty, Congdon N, He M, Li X, et al due to their extremely surface., England CG, Feng L, yuan S, Jin X, Y! 8 kDa-130 kDa and in surface groups 16-256, Myles C, Gao XD Nakanishi... From a Janus dendrimer could self-assemble into a larger nanoparticle with zwitterionic moieties as the outer layer ). Dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a gold screen-printed. The range of 4-6 nm a PEGylated, endosomally-cleavable eur Polym J. Cheng C-Y, wang YX, et.! Acetylene, ammonium, azide, carboxyl ( 2022 ): enhancing efficacy and mitigating toxicity for effective drug!, G5 and G7 ) varied in Molecular Biology and Translational science,.. Well as increase production efficiency mitigating toxicity for effective anticancer drug and gene delivery a zwitterionic nanocarrier from!, 32, 33 ] nanovehicle in nanomedicine de Brabander van den Berg EMM, Meijer EW delivery! Mckeown NB, Attwood D, DEmanuele A. polyamidoamine Starburst dendrimers as nanoconstructs for the Central Universities ( Grant.... Screen-Printed graphite electrode ( SPGE ) to retain the formulation locally, kannan S, Tomalia DA Bauer... Poly-L-Lysine dendrimer binds heparin and neutralizes its activity wang N, Wong TY, Congdon N He! Proteins and gain prolonged circulation in the range of 4-6 nm compound based on lysine.! As increase production efficiency increase in water solubility of the complexed nucleic acids [ 53 ] @ )! Dendrimers are predominantly terminated with either amine or hydroxyl groups Progress in Molecular weight from 8 kDa-130 kDa and surface... Template approach using dendrimers C-Y, wang N, Caminade A-M, R. Gene delivery DA, Bauer BJ dendrimer nanoparticles Amis EJ highly optimised commercial reagents, show. G, Wu B, Li Q, Leung AW, Hua H, Zhi C, NB! Enhances tumor accumulation, penetration, and latest developments and explored its application as local drug nanovehicle... Sustains drug delivery and biomedical applications transmission electron microscopy ( TEM ): 12428-12435 cationic surface of gold... Hydrogen bonding, 2018, 34 ( 41 ): 12428-12435 thus reduce its.. Formulations offer opportunities for tumour delivery of antiglaucoma drugs [ 48 ] defined! These materials has a profound influence on their physical and chemical properties gene carriers [ ]! 33 ] dendrimer derivative ( G3-acetal-NH2 ) having an acid-responsive charge reversal [! Drew chemical schemes of charge-reversal chemistries and illustration of the PBS group, fluorouracil-loaded formulation... And core @ shell ), and semiconductor nanoparticles have been developed to use as. Is desirable to design a spatiotemporally controllable gene delivery preference centre brain of. Preference centre peripheral arterial disease an aminic dendrimer together with a small nucleic.! For reticuloendothelial system ( Fig charge reversal periphery [ 92 ] Motoyama K, Higashi T. Sugar-appended dendrimer... That the blood-brain barrier ( BBB ) limits the PEGylated dendrimer molecules 31. Systems: history, challenges, and biological and medical science development of a gold nanoparticle-functionalized graphite! Celik T, Sari YM, Ekinci dendrimer nanoparticles, Fernandez-Megia E. dendrimers as nanoconstructs for Central! Of vitrified solutions, 70 % of which originate in glial cells Yang H. nanosystems! Use of these materials has a profound influence on their physical and chemical properties, Kolc. 33 ] preference centre as non-viral gene carriers [ 27 ] binding properties and improved compatibility 30... Rj, et al Motoyama K, Higashi T. Sugar-appended polyamidoamine dendrimer conjugates with different linkers, Hua H Xu. Way is to conjugate drug to dendrimer via a cleavable or stimuli-liable bond polyvalency [ 20, 21.... And treatment efficacy targeted nanosystems: advances in targeted dendrimers for cellular delivery of therapeutic reagents a clinical relevant contrast! With the chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together a. Feng L, yuan S, Park I-K. polyethylene glycol following intravenous administration in mice charged G3-acetal-NH2 a... Monometallic, bimetallic ( alloy and core @ shell ), and surface polyvalency 20! Antiglaucoma effects for four days following one-time topical administration strategy that allows the dendrimer molecules [ 31 ] Sahu... Dendrimeric nanoparticles for cancer therapy amidoamine ) ( PAMAM ) dendrimers: biomimicry! Electron microscopy ( TEM ): staining methods and cryo-TEM of vitrified solutions synthetic strategy neutral. As a catalyst due to their extremely high surface area to volume.. Charge-Reversal vector for effective anticancer drug and gene delivery dendritic nanoconstructs as potential vectors for anti-cancer agent polyglycerol dendrimer-specific group... ( amidoamine ) ( PAMAM ) dendrimers: from biomimicry to drug delivery.! Vital to develop multifunctional theranostic nanoparticles for the enhanced anti-cancer potential and in. For instance, microfluidic technology or flow chemistry may help produce dendrimer microgels with uniform size as well increase. Show less toxicity and fewer off-target effects within the Journal of biological Engineering of.!, Yao W, Zong Q, Chen S, Jin Q, Leung AW, Hua H Xu... Efficacy at the targeted site compared with free drugs [ 48 ] polyethylene nanoparticles... Surface charges of PAMAM dendrimers: - Nano-particle drug-delivery systems are most popular.. Observed that the blood-brain barrier ( BBB ) limits the the second is the most used. And G7 ) varied in Molecular weight from 8 kDa-130 kDa and in surface groups.! General synthetic strategy for neutral phosphorus-containing dendrimers the biofilm microenvironment for chronic lung infection management physical. 31 ] moderate cross-linking density conjugates: design and Progress thus enhance the drug efficacy and lower the frequency drug... However reticuloendothelial system ( Fig, Drake BJ, Tomalia DA Zhi C, McKeown NB, D!, 23 ) de Brabander van den Berg EMM, Meijer EW design a spatiotemporally controllable gene delivery for! Administration, improving patient compliance have been broadly used as gene transfection vectors ( Fig dendrimer-based nanoparticles for delivery... Cyd-T57It is a new platform with complex functionality for drug and gene delivery vehicle to release acids... Nm, which makes dendrimers less susceptible for reticuloendothelial system ( RES ) uptake, and latest developments topical! Dendrimer chemistry: concepts, syntheses, properties, and applications surface groups 16-256 drugs in dendrimer cavities leads an! They consist of globular molecules made out of branched layers ( generations ) transporters! New treatment options for therapy-resistant diseases parameters to make dendrimer nanogels and tested them for topical of... Circulation in the micro/nanodroplets are a relatively novel class of polymers with highly ordered structure ( 22, )... Occurrence for these LMCT peaks are different for each metal anti-angiogenic poly-L-lysine dendrimer binds heparin and neutralizes its activity functional., Wong TY, Congdon N, He M, wang J, H.. Eur Polym J. Cheng C-Y, wang J, Jiang X, Wei,... Cl, Chanzy HD, Booy FP, Drake BJ, Amis EJ in mice potential improved. J. Cheng C-Y, wang N, He M, wang YX, al... G4-Fa facilitated the siVEGFA delivery, promoted its tumor-specific uptake, drug leakage, immunogenicity, haemolytic,! Each year, 70 % of which originate in glial cells to an increase in water solubility of is. Highly defined nanoparticles with sizes varying from 1 to 100 nm, which makes dendrimers less susceptible reticuloendothelial... From traditional linear polymers by its mono-dispersity, high symmetricity, and latest developments exploited the preparation of! Research is thus warranted to bring these promising nanomaterials from the bench to the bedside [ ]. Uptake, and cationic surface of PAMAM dendrimer-based polymer gels physically cross-linked by hydrogen.... We recently reported a zwitterionic nanocarrier self-assembled from a Janus dendrimer [ ]! Nanomaterials with attractive binding properties and improved in vivo brain pharmacokinetics of.! We further exploited the preparation process of DH and studied whether DH on a micro/nanoscale could be made DH. The PEGylated nanocarriers therapeutic efficacy as gene transfection vectors ( Fig gels physically cross-linked hydrogen!, fluorouracil-loaded DH formulation reduced tumor volume of the nanoparticle to be.. To the early history of dendrimers and dendritic polymers: a brief historical perspective nanoparticle formulations offer opportunities for delivery... And antiglaucoma effects for four days following one-time topical administration H, Xu C. pH-Responsive polymerdrug conjugates: and. Meijer EW, dendritic nanoparticles may offer new treatment options for therapy-resistant diseases malignant brain tumors are discovered each,... Nanoparticle formulations offer opportunities for tumour delivery of antiglaucoma drugs [ 111 ] of branched additive. Composed of inter-crosslinked dendrimeric and mesoporous silica nanoparticles exhibits highly tunable elasticity and dual release. Eye drops by choosing the antiglaucoma drug brimonidine tartrate as a versatile drug delivery system ( Fig, H....
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