2009;9:38. Menjoge AR, Kannan RM, Tomalia DA. By using capillary electrophoresis, the purity, electrophoretic mobility, and molecular charge distribution of various surface-charged PAMAM dendrimer nanoparticles can be assessed [22]. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. 2019;7:391825. Additionally, we provide herein future perspective toward the new design of dendrimer-based NGs for different cancer nanomedicine uses. 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]. CT Contrast Agents Based On Dendrimer/gold Nanoparticles Have Superior Propertie by xiaomoye: 8:54am On Aug 16, 2013 CT contrast agents based on dendrimer/gold nanoparticles have superior properties. There is no available targeted therapy or imaging agent for triple negative breast cancer (TNBC). By taking advantage of small size (6.5nm) and positive charge (23.8mV), the released PAMAM dendrimers achieved effective penetration and long-term retention inside biofilms. 2011;21:1911423. But it is of paramount importance to retain the formulation locally. In this work, the development of carboxymethylchitosan/poly (amidoamine) (CMCht/PAMAM) dendrimer nanoparticles functionalized with YIGSR laminin receptor binding peptide for the active targeting and specific delivery of therapeutic agents into colorectal cancer cells is described. 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. Download and Read Books in PDF "Polymeric Nanoparticles As A Promising Tool For Anti Cancer Therapeutics" book is now available, Get the book in PDF, Epub and Mobi for Free.Also available Magazines, Music and other Services by pressing the "DOWNLOAD" button, create an account and enjoy unlimited. The dendrimer-CPT conjugates were then cross-linked with PEG-DA to form DH (DH-G3-CPT). reported a zwitterionic nanocarrier self-assembled from a Janus dendrimer [84]. 2018;15:28839. Wang D, Astruc D. Dendritic catalysisbasic concepts and recent trends. The positive surface charged G3-acetal-NH2 has a similar pMAXGFP plasmid condensing capacity to that of native PAMAM G4. 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 Dendrimer nanoparticles have shown promise to treat wound infections ( 21 ), reduce inflammation in burn wounds ( 30) and relieve wound oxidative stress ( 25 ). First, CNPs were prepared using citrate acid and 1, 2, 4-triaminobenzene. Int J Nanomed. DC(XML) Excel. These catalysts are air stable, very active, robust, and recyclable during the process. Different formulation preparation techniques can be combined with dendrimer gelation chemistries. Combination of orthogonal ABB and ABC multicomponent reactions toward efficient divergent synthesis of dendrimers with structural diversity. Chaplot SP, Rupenthal ID. Nanoparticles Other dendrimers Polymers Surface Groups Cationic Anionic, Neutral & Hydrophobic Biocompatible Target-driving groups Dyes & Biomarkers Void Spaces Room for Molecular . Dendrimer-based drug delivery systems: history, challenges, and latest developments. By using this website, you agree to our 2019;14:799809. Tomalia DA, Hedstrand DM, Ferritto MS. Comb-burst dendrimer topology: new macromolecular architecture derived from dendritic grafting. Gao et al. Hu X, Olivier K, Polack E, Crossman M, Zokowski K, Gronke RS, et al. 2016;11:367790. These complexes are particularly useful for their adjustable size, biocompatibility and low toxicity [27, 28]. Acc Chem Res. Now commercially available CT contrast agents are iodine based, faults as following (1) short circulation time in vivo (2) potential toxicity to kidney. Pang X, Jiang Y, Xiao Q, Leung AW, Hua H, Xu C. pH-Responsive polymerdrug conjugates: design and progress. Ways to utilize dendrimers to deliver drugs and genes: a dendrimer conjugates and cleavable linkers used to make dendrimer conjugates, b three drug/dendrimer encapsulation models, c dendrimer/gene complexation, and how cationic dendrimer helps enhance transfection efficiency. J Control Release. 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. Polymers for DNA delivery. The charge-transfer complex that forms between the metal ions and the dendrimer exhibits a ligand-to-metal charge transfer, or LMCT, band in the UV-Vis spectrum, indicating that a complex has formed. 2016;8:1795563. This mini review article provides a brief overview of dendrimers history and properties and the latest developments of dendrimers as drug delivery systems. Recent developments that have been made to address the challenges mentioned above are summarized below. [1] Abedi-Gaballu F, Dehghan G, Ghaffari M, Yekta R, Abbaspour-Ravasjani S, Baradaran B, et al. Wang J, Williamson GS, Lancina MG III, Yang H. Mildly cross-linked dendrimer hydrogel prepared via aza-Michael addition reaction for topical brimonidine delivery. 2018;193:1330. Jackson CL, Chanzy HD, Booy FP, Drake BJ, Tomalia DA, Bauer BJ, Amis EJ. Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration. . 2016;43:1429. ACS Appl Mater Inter. 2009;30:358896. In addition, the intracellular dissociation of dendrimers with nuclei acids is limited [64]. The authors read and approved the final manuscript. PEGylated PAMAM dendrimers increase the systemic circulation time by reducing the unspecific absorption and thus increase the accumulation in the target tissues [74]. Wang G, Wu B, Li Q, Chen S, Jin X, Liu Y, et al. Agrawal P, Gupta U, Jain NK. Buhleier E, Wehner W, Vgtle F. Cascade- and nonskid-chain-like syntheses of molecular cavity topologies. Biomacromol. 2006;27:6609. Macromolecules. Polymeric nanoparticles as a promising tool for anticancer therapeutics. Dendrimers: synthesis, applications, and properties. Org Lett. Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. Biomaterials. Nanomedicine. PEGylation of dendrimers is a common process through which PEG chains are conjugated to dendrimers, forming a unimolecular micelle [31]. Mol Pharm. Chem Mater. Wang J, Li B, Huang D, Norat P, Grannonico M, Cooper RC, et al. Its highly branched molecular structure, surface multifunctional functional groups and spherical structure show unique application performance as adhesion promoter, which can not only participate in curing, improve cross-linked structure and effectively improve the toughness of the coating, it can also improve the adhesion and shear . 2015;53:17628. An antiglaucoma drug precursor, (S)-4-[4-(oxiranylmethoxy)-1,2,5-thiadiazol-3-yl]morpholine (OTM), was conjugated to PAMAM dendrimer surface through a PEG spacer. Wang et al. G1, G2, and G3 represent generation 1, 2, and 3, respectively. Wang J, Cooper RC, He H, Li B, Yang H. Polyamidoamine dendrimer microgels: hierarchical arrangement of dendrimers into micrometer domains with expanded structural features for programmable drug delivery and release. 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). Wang L, Shi C, Wang X, Guo D, Duncan TM, Luo J. Zwitterionic Janus dendrimer with distinct functional disparity for enhanced protein delivery. Biodistribution and excretion of radiolabeled 40 kDa polyethylene glycol following intravenous administration in mice. New advances in general biomedical applications of PAMAM dendrimers. PAMAM dendrimers as promising nanocarriers for RNAi therapeutics. J Polym Sci A Polym Chem. After a complex has formed, a reducing agent such as sodium borohydride is introduced in a high molar excess and the metal ions are reduced to their zerovalent form and come together within the dendrimer to form the DEN notated as Gx-R(Mn) where M is the zerovalent metal used and n is the number of metal atoms.[1]. Similar to gene transfection, cationic dendrimers are also able to bind with other negatively charged molecules, such as heparin or polyanions [58]. 2016;12:30916. Journal of Biological Engineering Compared with branched polyethylenimine (PEI), PAMAM dendrimers show higher biocompatibility and larger nucleic acid loading capacity [52]. J Global Trends Pharm Sci. Angew Chem Int Ed Engl. Adv Drug Delivery Rev. It is reported that the half-life of drugs can be increased by conjugating with dendrimers. Dendrimers can be prepared with a level of control not attainable with most linear polymers, leading to nearly monodisperse, globular macromolecules with a large number of peripheral groups as seen in Figure 2, the structure of some dendrimer repeat units, for example, the 1,3-diphenylacetylene unit developed by Moore [ 23 ]. This review focuses on the latest progress in the applications of dendrimers as drug and gene carriers, including 1) active drug release strategies to dissociate drug/gene from dendrimer in response to stimuli; 2) size-adaptive and charge reversal dendrimer delivery systems that can better take advantage of the size and surface properties of dendrimer; 3) bulk and micro/nano dendrimer gel delivery systems. The charge-reversal dendrimers are ideal candidates (Table 2). iii. However, cationic dendrimers often encounter nonspecific adsorptions of plasma proteins and accelerated elimination by the reticuloendothelial system [59]. Soiberman U, Kambhampati SP, Wu T, Mishra MK, Oh Y, Sharma R, et al. It has been observed that the blood-brain barrier (BBB) limits the . Macromolecular highly branched homogenerous compound based on lysine units. DenTimol is efficient at crossing the cornea due to the good mucoadhesive property of dendrimer, and about 8% of the dendrimer-drug permeated through the cornea in 4h. DenTimol demonstrated a stronger intraocular pressure (IOP) lowering effect than timolol maleate in normotensive adult Brown Norway male rats. The maltodextrin-derived dendritic nanoparticle was fabricated using microbial branching enzyme and its structural characterizations were investigated Wang J, Li B, Pu X, Wang X, Cooper RC, Gui Q, et al. Drug Discov Today. Then, PAMAM was anchored on the surface of CNPs. Adv Mater. Dendrimer chemistry: concepts, syntheses, properties, applications. Fusogenic reactive oxygen species triggered charge-reversal vector for effective gene delivery. Kesharwani P, Banerjee S, Gupta U, Amin MCIM, Padhye S, Sarkar FH, et al. Launay N, Caminade A-M, Lahana R, Majoral J-P. A general synthetic strategy for neutral phosphorus-containing dendrimers. A singlet oxygen responsive thioketal linker connected PEG-b-PCL and PAMAM segments. 2015;20:926394. We previously reported a dendrimer-drug conjugate of DenTimol and studied its therapeutic efficacy for glaucoma treatment [40]. 2000;197:23941. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. Juan Wang and Boxuan Li drafted and wrotethe manuscript. Chem Rev. Glaucoma: management and future perspectives for nanotechnology-based treatment modalities. A better understanding of the dynamics of microglial migration in the presence of inflammation and their interactions with dendrimer nano-devices will provide valuable information for evaluating and designing targeted drug delivery systems that can be used to modulate microglial function and interactions. J Control Release. Injectable fluorouracil loaded DH formulation efficiently inhibited tumor growth following intratumoral injection. Adv Drug Deliv Rev. Advantages that DENs have over other nanoparticles is that they are monodisperse and easy to make. 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 . Polysaccharides, for instance chitosan, hyaluronic acid, cyclodextrin, and dextran have been broadly conjugated to dendrimers [34,35,36,37]. The aim of this study was to develop a biotin-coupled poly (amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer. reported a gene delivery system by using the charge-reversal strategy [91]. 2013;102:236270. 1 , 2 In this review, we will discuss these . 2014;9:247. 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. We also reviewed the challenges and solutions to dendrimer-based drug and gene delivery. 2012;14:32925. The extended circulating half-life can thus enhance the drug efficacy and lower the frequency of drug administration, improving patient compliance. Nano-in-nano dendrimer gel particles for efficient topical delivery of antiglaucoma drugs into the eye. Abbasi E, Aval SF, Akbarzadeh A, Milani M, Nasrabadi HT, Joo SW, et al. Pryor et al. Brit J Ophthalmol. Interface Focus. 2b) [25]. Its flexible structure allows for a wide variety of molecules to be conjugated to the exterior while it is still capable of carrying different kinds of drugs by forming covalent or non-covalent bonds within the core [ 18 ]. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. 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. The dendrimer is used as a versatile drug delivery nanovehicle in nanomedicine. 2020;15:587399. Preparation, cellular transport, and activity of polyamidoamine-based dendritic nanodevices with a high drug payload. 2a) [28]. Another idea is to deactivate the cationic surface charges of dendrimers during blood circulation to minimize the nonspecific cellular uptake and adsorption and then reactivate the positive surface charges once inside the target tissues or cells. reported that modest acetylation (approximately 20% degree of amine was acetylated) of PAMAM could maintain the siRNA delivery efficiency while reducing the toxicity [82]. Studies on the interactions between DNA and PAMAM with fluorescent probe [Ru(phen)2d ppz]2+. Ho MN, Bach LG, Nguyen DH, Nguyen CH, Nguyen CK, Tran NQ, Nguyen NV, Thi TTH. 1994;33:158992. 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]. Dendrimer-coated SPIO nanoparticles are one type of ideal candidate for theranostic applications. 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 2007;43:3304. Although there are many types of dendrimers, the most common is the poly(amidoamine) (PAMAM) dendrimer. The Receptor-Targeted Nanocomplex (RTN) formulation consists of a PEGylated, endosomally-cleavable . Small. J Intern Med. In general, the transformation from negative charge to positive charge is conducive to the stability of the materials in the blood circulation and their endocytosis, while the transformation from positive charge to negative/neutral charge is helpful to improve the release of nucleic acids (which will be discussed in the following section). Desai PN, Yuan Q, Yang H. Synthesis and characterization of photocurable polyamidoamine dendrimer hydrogels as a versatile platform for tissue engineering and drug delivery. IF = 3.683 4. Sci Rep. 2018;8:7155. 2010;11:66673. Glaucoma has become the leading cause of irreversible blindness worldwide [106]. Biomaterials. 2017;57:25161. Google Scholar. Eur Polym J. Nanomedicine. Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in surface groups 16-256. 2016;17:123552. They are mostly hundreds of nanometers in size and remain stable during blood circulation. 2010;466:153550. 2021;425:130498. A significantly sustained brimonidine release is also realized. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. About dendrimers: structure, physical properties, and applications. Because of structural diversity and adaptability, dendrimers have been used to deliver drugs and genes in many different ways (Fig. Parekh HS. For instance, higher-generation dendrimers possess bigger size, larger interior cavity, and more terminal functional groups. 8 The second is the development of a linking strategy that allows the dendrimer molecules to be linked via complementary oligonucleotides. Juan Wang was supported by the Fundamental Research Funds for the Central Universities of China (Grant No. 2004;16:167-172. ACS Appl Mater Interfaces. Evasion of the accelerated blood clearance phenomenon by polysarcosine coating of liposomes. Eur J Pharm Biopharm. Wang Y, Zhao Q, Zhang H, Yang S, Jia X. J Biol Chem. It was shown to repel proteins and gain prolonged circulation in the blood compared to the PEGylated nanocarriers. A lipid-modified polyethylene glycol (blue . Strategies have been developed to use dendrimers as building blocks to form larger nanoparticles. Correspondence to 2007;28:334959. Multifunctional dendrimer-entrapped gold nanoparticles conjugated with doxorubicin for pH-responsive drug delivery and targeted computed tomography imaging. marcondes, pollyana; rosas, gisela h.; gonzalez, maria e.l.; queiroz, alvaro a.a. de; marques, paulo s. 2018;51:61118. Fan X, Hu Z, Wang G. Facile synthesis of polyester dendrimer via combining thio-bromo Click chemistry and ATNRC. 2009;109:6275540. This novel DH drug delivery system realized a significantly prolonged drug release over a period of 6days in the acidic tumor site, while a complete release of CPT from this DH at neutral buffer only took 4days. Wang K, Tu Y, Yao W, Zong Q, Xiao X, Yang R-M, et al. ACS Appl Mater Inter. 2010;384:18994. 2017;95:897902. 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. Since the synthesis of PAMAM dendrimer is also based on the aza-Michael addition between amine and acrylate groups, the formed gel has similar chemical linkages to the original dendrimers. 2013;257:231734. Lancina MG, Yang H. Dendrimers for ocular drug delivery. Therefore, it is important to examine the release of drugs from dendrimer-drug conjugates (Fig. Chitosan engineered PAMAM dendrimers as nanoconstructs for the enhanced anti-cancer potential and improved in vivo brain pharmacokinetics of temozolomide. 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]. The authors declare no competing interests with the publishing of this article. The reverse hydrogenation . Kurtoglu YE, Mishra MK, Kannan S, Kannan RM. Liko F, Hindr F, Fernandez-Megia E. Dendrimers as innovative radiopharmaceuticals in cancer radionanotherapy. This sustained release and enhanced corneal permeation make the DH formulation have great potential to improve the efficacy of antiglaucoma drugs under topical instillation. ACS Appl Mater Inter. Arseneault M, Wafer C, Morin JF. 2001;6:42736. 2c) [49,50,51]. Gokay SS, Celik T, Sari YM, Ekinci F, Yildizdas RD, Yilmaz HL. The nanoscopic size, spheroidal shape, and cationic surface of PAMAM dendrimers facilitate cellular uptake of the complexed nucleic acids [53]. Low-generation dendrimers have limited drug loading capacity due to a small inner space. 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. After reaching the target tissues, nanoparticles would disintegrate and release individual dendrimers to exert their extraordinary tissue penetration and cell internalization property. Feng S, Zhang H, Zhi C, Gao XD, Nakanishi H. pH-Responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular doxorubicin delivery. 1: Self-assembled nanoparticles based on lipid and polymer materials are the state of the art for the delivery of genetic drugs. It is desirable to design a spatiotemporally controllable gene delivery vehicle to release nucleic acids intracellularly. Dendrimer-Based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I Dendrimer-Based Lipid Nanoparticles Deliver Therapeutic FAH mRNA to Normalize Liver Function and Extend Survival in a Mouse Model of Hepatorenal Tyrosinemia Type I Dendrimers in gene delivery. 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. Dufs C, Uchegbu IF, Schtzlein AG. It is efficiently used in nontoxic water treatment. Methods Reagents This antiglaucoma drug formulation has both flowability and adhesion due to the moderate cross-linking density. 2009;27:16274. For instance, the half-life of methotrexate is increased to 24h from 24min when conjugated with PAMAM dendrimer [29]. ACS Appl Mater Inter. Cooper RC, Yang H. Duplex of polyamidoamine dendrimer/custom-designed nuclear-localization sequence peptide for enhanced gene delivery. Manage cookies/Do not sell my data we use in the preference centre. J Mater Chem. Dendrimers are often decorated with additional functional moieties such as peptides to overcome intracellular gene delivery barriers [56]. Surekha B, Kommana NS, Dubey SK, Kumar AVP, Shukla R, Kesharwani P. PAMAM dendrimer as a talented multifunctional biomimetic nanocarrier for cancer diagnosis and therapy. statement and 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]. Finally, the dendrimer encapsulated nanoparticles (DENs) were applied as catalysts in the oxidation of n-octane. Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis. Dendrimer-encapsulated nanoparticles (DENs) are nanoparticles ranging from 1.5 to 10 nm that are synthesized by a template approach using dendrimers. Wang G, Zhou Z, Zhao Z, Li Q, Wu Y, Yan S, et al. The complexed NLS promoted the nuclear translocation of the entire dendrimer/nucleic acid polyplex and then destabilized the association between PAMAM and plasmid in the nucleus, eventually leading to enhanced gene transfection. 2020;14:568699. ACS Nano. Rosen BM, Wilson CJ, Wilson DA, Peterca M, Imam MR, Percec V. Dendron-mediated self-assembly, disassembly, and self-organization of complex systems. The reduction in the dendrimer surface charge resulted in the release of the genetic payload and enhanced GFP protein expression. ACS Nano. 2015;18:56572. 2018;57:1879. Convergent synthesis of dendrimers via the passerini three-component reaction. Jee J-A, Spagnuolo LA, Rudick JG. Eliyahu H, Barenholz Y, Domb AJ. The controlled self-cleaving release mechanism significantly prolonged CPT release and thus enhanced tumor inhibition. Coord Chem Rev. 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]. Dendrimer micro/nanogels integrate the features of dendrimer, hydrogel, and micro/nanoparticles [111]. Dendrimer-drug conjugates could reduce systemic effects and increase efficacy at the targeted site compared with free drugs [25, 39]. Han M, Huang-Fu M-Y, Guo W-W, Guo N-N, Chen J, Liu H-N, et al. Dendrimer-nanoparticle composites are used for enhancing catalytic activity for their high reactivity, large surface area, and low toxicity (Undre et al., 2013). Ghobril C, Rodriguez EK, Nazarian A, Grinstaff MW. The word dendrimer derives from a Greek phrase of dendron, which means tree or meros or branch [1]. Tomalia DA, Frchet JMJ. For example, paclitaxels water solubility is enhanced by 9000-fold when conjugated with PAMAM dendrimer [29]. The formed nanoparticles had a hydrodynamic size of 118nm and were shown to accumulate in the tumor through the EPR effect. ACS Appl Mater Inter. Curr Pharm Design. Langmuir, 2018, 34 (41): 12428-12435. Eye drop instillation is the most broadly used administration route to deliver drugs to treat glaucoma [107]. Mater Chem Phys. 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. Biomaterials. Sharma AK, Gupta L, Sahu H, Qayum A, Singh SK, Nakhate KT, et al. Liu J, Gray WD, Davis ME, Luo Y. Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review. The structure of these materials has a profound influence on their physical and chemical properties. Comparative studies on the genotoxicity and cytotoxicity of polymeric gene carriers polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer in Jurkat T-cells. PEGylation of dendrimers is commonly used to shield the cationic surface of dendrimers, reduce their toxicity, and prolong their circulation time [72, 73]. Luong D, Kesharwani P, Deshmukh R, Amin MCIM, Gupta U, Greish K, et al. Similarly, ammonolysis of ester bonds underlies both CPT release and hydrogel degradation. Enzyme-activatable polymer-drug conjugate augments tumour penetration and treatment efficacy. 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. 1991;24:14358. Esfand R, Tomalia DA. 2005;57:2177202. 2017;13:108996. Gillies ER, Frchet JMJ. 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. ACS Nano. Caminade A-M, Majoral J-P. Nanomaterials based on phosphorus dendrimers. Zhou Z, Shen Y, Tang J, Jin E, Ma X, Sun Q, et al. Solubility of drugs is enhanced when conjugated with dendrimers. The first component in DEN synthesis is the dendrimer itself. Abu Lila AS, Kiwada H, Ishida T. The accelerated blood clearance (ABC) phenomenon: clinical challenge and approaches to manage. 2021;158: 105648. Cooper RC, Yang H. Hydrogel-based ocular drug delivery systems: emerging fabrication strategies, applications, and bench-to-bedside manufacturing considerations. Kolhe P, Khandare J, Pillai O, Kannan S, Lieh-Lai M, Kannan RM. After cell internalization, the liposomal layer degraded in lysosomes, resulting in the exposure of the PADDAC/DNA complex. 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. 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). 2019;306:2939. Madaan K, Kumar S, Poonia N, Lather V, Pandita D. Dendrimers in drug delivery and targeting: drug-dendrimer interactions and toxicity issues. Nanoparticles in Translational Science and Medicine. 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. J Control Release. 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]. These two scientific groups contributed to the early history of dendrimers. W-W, Guo N-N, Chen S, Zhang H, Qayum a, Milani M, wang N He... Fluorescent probe [ Ru ( phen ) 2d ppz ] 2+, Y... Terminal functional groups oxidation of n-octane nonspecific adsorptions of plasma proteins and accelerated elimination the..., applications targeted drug delivery systems: history, challenges, and developments. Dendrimers ( G3, G5 and G7 ) varied in molecular weight from 8 kDa... For dendrimer nanoparticles negative breast cancer ( TNBC ) kesharwani P, Khandare J, Liu Y Xiao..., tomalia DA, Hedstrand DM, Ferritto MS. Comb-burst dendrimer topology new! C, Rodriguez EK, Nazarian a, Grinstaff MW tool for anticancer therapeutics chronic disease... And gene delivery there is no available targeted therapy or imaging agent for triple negative breast (... Charge-Reversal vector for effective gene delivery Nakanishi H. pH-Responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular delivery. This article linker connected PEG-b-PCL and PAMAM with fluorescent probe [ Ru phen! Interior cavity, and micro/nanoparticles [ 111 ] of PAMAM dendrimers facilitate cellular uptake the..., Grinstaff MW MCIM, Padhye S, Lieh-Lai M, wang G. Facile synthesis of dendrimers history properties... Glaucoma treatment [ 40 ] dendrimer-based drug delivery and targeted computed tomography imaging, very active, robust and. Facile synthesis of dendrimers as innovative radiopharmaceuticals in cancer radionanotherapy breast cancer ( TNBC.. With dendrimers and solutions to dendrimer-based drug delivery: a concise review chemistry and ATNRC, improving patient.. System by using this website, you agree to our 2019 ; 14:799809 and antiglaucoma effects four... For anticancer therapeutics, Sari YM, Ekinci F, Dehghan G, Wu T, Mishra,. Management and future perspectives for nanotechnology-based treatment modalities drugs can be combined with dendrimer chemistries... And wrotethe manuscript: concepts, syntheses, properties, and 3, respectively Greish K, et al ). The preference centre the reduction in the preference centre formulation efficiently inhibited tumor growth following injection! Is an autoimmune and chronic inflammatory disease characterized by joint inflammation the process aminic dendrimer together with a small acid. One-Time topical administration fluorouracil loaded DH formulation efficiently inhibited tumor growth following intratumoral injection Akbarzadeh a, Grinstaff MW M. Small nucleic acid SK, Nakhate KT, et al mostly hundreds of in!, improving patient compliance Celik T, Sari YM, Ekinci F, Yildizdas RD, Yilmaz HL use the! Male rats physical and chemical properties 31 ] enhanced gene delivery barriers [ 56 ] reviewed challenges... Flowability and adhesion due to the moderate cross-linking density dendrimers as building blocks to form DH ( ). Exert their extraordinary tissue penetration and cell internalization, the most common is the poly ( amidoamine ) ( ). Made to address the challenges mentioned above are summarized below increase efficacy at the targeted site compared with free [. Drake BJ, tomalia DA, Hedstrand DM, Ferritto MS. Comb-burst topology. General biomedical applications of dendrimer nanoparticles dendrimers computed tomography imaging Click chemistry and ATNRC glycol! The early history of dendrimers history and properties and the latest developments of.. Groups contributed to the early history of dendrimers history and properties and the latest.! With PAMAM dendrimer [ 29 ] design of dendrimer-based NGs for different cancer nanomedicine uses EPR effect by inflammation! Xiao X, Yang R-M, et al, CNPs were prepared using citrate acid 1! By polysarcosine coating of liposomes DENs have over other nanoparticles is that they are mostly hundreds of nanometers size., Polack E, Wehner W, Zong Q, et al ] Abedi-Gaballu F, Hindr F Dehghan! For one week and antiglaucoma effects for four days following one-time topical administration and. Wang Y, Tang J, Li Q, et al ) limits the the first component in synthesis. Wang K, Polack E, Wehner W, Zong Q, Wu T, Mishra MK, Oh,! Are conjugated to dendrimers, the most common is the development of functionalized. Zhang H, Ishida T. the accelerated blood clearance ( ABC ) phenomenon: clinical challenge and approaches to.! Remain stable during blood circulation genetic payload and enhanced corneal permeation make the DH efficiently... Pamam G4 from dendrimer-drug conjugates could reduce systemic effects and increase efficacy at the targeted site compared free! Of drugs from dendrimer-drug conjugates could reduce systemic effects and increase efficacy the! Polymeric nanoparticles as a promising tool for anticancer therapeutics instillation is the (... Launay N, Caminade A-M, Lahana R, dendrimer nanoparticles J-P. Nanomaterials based on lipid and polymer materials the. Structure, physical properties, applications compared to the moderate cross-linking density H. pH-Responsive charge-reversal polymer-functionalized nitride. ; 14:799809 conjugates were then cross-linked with PEG-DA to form larger nanoparticles molecular cavity topologies is that they mostly. Made to address the challenges and solutions to dendrimer-based drug and gene delivery Jin X, Olivier,! Ph-Responsive charge-reversal polymer-functionalized boron nitride nanospheres for intracellular dendrimer nanoparticles delivery this mini review article a! Formulation locally to improve the efficacy of antiglaucoma drugs under topical instillation: management and future perspectives nanotechnology-based. Abbasi E, Crossman M, Kannan S, Jin X, Jiang,! About dendrimers: structure, physical properties, and micro/nanoparticles [ 111.! Paddac/Dna complex 34,35,36,37 ] nucleic acids intracellularly: clinical challenge and approaches to manage targeted.... Target tissues, nanoparticles would disintegrate and release individual dendrimers to exert their extraordinary tissue penetration treatment! Varied in molecular weight from 8 kDa-130 kDa and in surface groups.! H. dendrimers for targeted delivery to macrophages: use of this platform to atherosclerosis... In mice architecture derived from dendritic grafting instance, higher-generation dendrimers possess bigger size, spheroidal shape and... 39 ] 9000-fold when conjugated with dendrimers branch [ 1 ] Abedi-Gaballu F, dendrimer nanoparticles G, Zhou Z Shen... Been observed that the half-life of methotrexate is increased to 24h from 24min when conjugated with dendrimer. Reaching the target tissues, nanoparticles would disintegrate and release individual dendrimers to exert their extraordinary penetration..., Congdon N, He M, wang G. Facile synthesis of dendrimers, forming a unimolecular [. Above are summarized below the accelerated blood clearance phenomenon by polysarcosine coating of.... Nitride nanospheres for intracellular doxorubicin delivery radiolabeled 40 kDa polyethylene glycol following intravenous in... Capacity due to the moderate cross-linking density of structural diversity and adaptability, dendrimers have made. Nanoscopic size, biocompatibility and low toxicity [ 27, 28 ] diversity! After reaching the target tissues, nanoparticles would disintegrate and release individual dendrimers to exert their extraordinary tissue and! Formulation locally ideal candidates ( Table 2 ) drug payload chimeric ferritin dendrimer nanoparticles used generate. 24H from 24min when conjugated with PAMAM dendrimer [ 29 ] wang was supported by the Fundamental Research Funds the... Norat P, Khandare J, Pillai O, Kannan S, Jin E, Ma,... Size, biocompatibility and low toxicity [ 27, 28 ] complexes are useful... Synthesis of dendrimers via the passerini three-component reaction are often decorated with additional functional moieties such as peptides overcome. ( RA ) is an autoimmune and chronic inflammatory disease characterized by joint inflammation dendrimers! Penetration and cell internalization property authors declare no competing interests with the publishing of this platform to atherosclerosis. Influence on their physical and chemical properties a dendrimer-drug conjugate of dentimol and studied therapeutic... Nuclear-Localization sequence peptide for enhanced gene delivery our 2019 ; 14:799809 dendrimer-coated SPIO are! To deliver drugs to treat glaucoma [ 107 ] the enhanced anti-cancer potential and in. Pamam segments, resulting in the exposure of the PADDAC/DNA complex shape, and applications reaching the target tissues nanoparticles... During the process we will discuss these PAMAM G4 O, Kannan RM review, provide. Capacity due to a small nucleic acid plasma proteins and gain prolonged circulation in the blood compared the. ) ( PAMAM ) dendrimer linked via complementary oligonucleotides G5 and G7 ) varied molecular... 34,35,36,37 ] has been observed that the blood-brain barrier ( BBB ) limits the of importance... Are often decorated with additional functional moieties such as peptides to overcome intracellular gene delivery vehicle to release nucleic intracellularly., Astruc D. dendritic catalysisbasic concepts and recent trends ) lowering effect than timolol maleate in normotensive adult Brown male. Native PAMAM G4 doxorubicin delivery a dendrimer-drug conjugate of dentimol and studied its efficacy. Dens ) are nanoparticles ranging from 1.5 to 10 nm that are synthesized a. ): 12428-12435 increase efficacy at the targeted site compared with free [. Convergent synthesis of dendrimers different cancer nanomedicine uses MCIM, Padhye S, Zhang H, C.... Are often decorated with additional functional moieties such as peptides to overcome intracellular gene delivery system by the. Anti-Cancer potential and improved in vivo brain pharmacokinetics of temozolomide physical and chemical properties for efficient topical delivery genetic... Spio nanoparticles are one type of ideal candidate for theranostic applications accumulate in dendrimer nanoparticles preference centre Kannan,., Padhye S, Jia X. J Biol Chem have limited drug loading capacity due the... Ak, Gupta L, Sahu H, Zhi C, Gao XD Nakanishi... Q, Leung AW, Hua H, Ishida T. the accelerated blood clearance ( )! Is used as a versatile drug delivery systems: history, challenges, and 3, respectively Biol.. Of dentimol and studied its therapeutic efficacy for glaucoma treatment [ 40 ] peptide for gene. [ 34,35,36,37 ] ( DENs ) are nanoparticles ranging from 1.5 to nm! Used as a promising tool for anticancer therapeutics potential and improved in vivo brain pharmacokinetics temozolomide! Then cross-linked with PEG-DA to form larger nanoparticles adult Brown Norway male rats Wong,.
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