Biomedical applications of dendrimers: a tutorial. 4). Transl Res. Arima H, Motoyama K, Higashi T. Sugar-appended polyamidoamine dendrimer conjugates with cyclodextrins as cell-specific non-viral vectors. 2014;3:66770. Buhleier E, Wehner W, Vgtle F. Cascade- and nonskid-chain-like syntheses of molecular cavity topologies. Agrawal P, Gupta U, Jain NK. 2019;306:2939. Interface Focus. The word dendrimer derives from a Greek phrase of dendron, which means tree or meros or branch [1]. Jackson CL, Chanzy HD, Booy FP, Drake BJ, Tomalia DA, Bauer BJ, Amis EJ. Soiberman U, Kambhampati SP, Wu T, Mishra MK, Oh Y, Sharma R, et al. 25 Treatment of rat liver cell line with silver nanoparticles resulted in membrane damage, re-duced glutathione levels, and increase in ROS produc- Angew Chem Int Ed Engl. marcondes, pollyana; rosas, gisela h.; gonzalez, maria e.l.; queiroz, alvaro a.a. de; marques, paulo s. 2003;278:4482631. Dendrimers are a relatively novel class of polymers with highly ordered structure ( 22, 23 ). Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. Wang J, Li B, Huang D, Norat P, Grannonico M, Cooper RC, et al. J Control Release. These two scientific groups contributed to the early history of dendrimers. 2011;40:17390. Monometallic, bimetallic and semiconductor nanoparticles have been synthesized using this method. Wang D, Astruc D. Dendritic catalysisbasic concepts and recent trends. Therefore, they have been broadly used in designing cleavable dendrimer-drug conjugates [42,43,44,45]. J Control Release. Parekh HS. 2009;9:38. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in surface groups 16-256. ACS Appl Mater Inter. Juan Wang was supported by the Fundamental Research Funds for the Central Universities of China (Grant No. Gao Y, Wang J, Chai M, Li X, Deng Y, Jin Q, 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 . Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, et al. The sustainability of energy conversion inhibition for tumor ferroptosis therapy and chemotherapy. 2014;9:247. 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. Deng X-X, Du F-S, Li Z-C. Cong H, Zhou L, Meng Q, Zhang Y, Yu B, Shen Y, et al. Acta Biomater. Dendrimer-based metal complexes are now expected to be promising components for the design of new materials. Dendritic nanoparticles have been developed with auspicious properties like high loading capacity for guest molecules, low polydispersity and tunable end groups. 2011;21:1911423. Tomalia DA, Frchet JMJ. Macromolecules. 2004;37:3418. For instance, dendrimers with a hydrophobic core and a hydrophilic periphery may behave like unimolecular micelles, and they have been utilized to solubilize hydrophobic drugs by entrapping them in the intramolecular cavity [25, 26]. Recently, we developed a DH platform using the aza-Michael addition cross-linking strategy and explored its application as local drug delivery system(Fig. Cited 10 time in Cited 0 time in . If drugs can be cleaved from dendrimer-drug conjugates and maintain their initial structure, this bureaucratic regulation issue could be avoided. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. It has been observed that the blood-brain barrier (BBB) limits the . It is efficiently used in nontoxic water treatment. Pooresmaeil M, Namazi H. Advances in development of the dendrimers having natural saccharides in their structure for efficient and controlled drug delivery applications. Waite CL, Sparks SM, Uhrich KE, Roth CM. About dendrimers: structure, physical properties, and applications. 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). Esfand R, Tomalia DA. [ Google Scholar] Articles from Oncotarget are provided here courtesy of Impact Journals, LLC Other Formats PubReader PDF (5.5M) Actions Cite Favorites Share RESOURCES Similar articles Complying with the most modern trends that suggest using nanotechnology, dendrimer nanoparticles were selected as a device to obtain an ETO drug delivery system (DDS) with a more promising Z-potential and an improved DL% in comparison to that previously achieved. This is the basis for making charge-reversal or charge-switchable dendrimers. Hsieh-Chih Tsai, Toyoko Imae, in Progress in Molecular Biology and Translational Science, 2011. . They are mostly hundreds of nanometers in size and remain stable during blood circulation. 2012;134:176807. PEGylated PAMAM dendrimers increase the systemic circulation time by reducing the unspecific absorption and thus increase the accumulation in the target tissues [74]. 2020;12:1482538. Zhou L, Gan L, Li H, Yang X. 2010;15:17185. A homogeneous dendrimer hydrogel: cross-linking strategy, tunable functionality, and application for local drug delivery system. Academic Press; 2019. p. 20531. For instance, microfluidic technology or flow chemistry may help produce dendrimer microgels with uniform size as well as increase production efficiency. Wang L, Shi C, Wang X, Guo D, Duncan TM, Luo J. Zwitterionic Janus dendrimer with distinct functional disparity for enhanced protein delivery. They consist of globular molecules made out of branched layers (generations). 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. Appl Mater Today. 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]. In addition, increasing evidence shows that the excessive use of PEG may lead to the production of PEG antibodies in the body, causing accelerated blood clearance (ABC) and shortening blood circulation time of PEGylated materials [79,80,81]. Solubility of drugs is enhanced when conjugated with dendrimers. They provide a new platform with complex functionality for drug and gene delivery. IF = 3.683 4. For instance, size-switchable or adaptive nanoparticles obtained from dendrimer clusters have attractive features [69, 70]. Org Lett. Then, PAMAM was anchored on the surface of CNPs. These are overcome by surface engineering the dendrimer such as Polyester dendrimer, Glyco-dendrimers, PEGylated In: Kesharwani P, Paknikar KM, Gajbhiye V, editors. First, CNPs were prepared using citrate acid and 1, 2, 4-triaminobenzene. Terms and Conditions, Macromolecular highly branched homogenerous compound based on lysine units. 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. 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. PAMAM dendrimers as promising nanocarriers for RNAi therapeutics. 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]. They are composed of an internal core and branching dendrons with surface active groups which can be functionalized for medical applications. Dendrimers for gene deliverya potential approach for ocular therapy? 2002;40:271928. Chapter Amine-terminated PAMAM dendrimers have been broadly used as gene transfection vectors (Fig. Subconjunctival injectable dendrimer-dexamethasone gel for the treatment of corneal inflammation. Drug Chem Toxicol. Biomacromol. Emerging nanoparticles as drug delivery systems. In this new formulation, CPT was covalently grafted to PAMAM dendrimer. Dendrimers were applied (0.2% concentration) in aqueous solutions or cosmetic formulation onto viable pig or human cadaver skin assembled in diffusion cells. 2018;23:2849. PAMAM dendrimers selected for comparison included G3 (7 kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). 2010;384:18994. Further research is thus warranted to bring these promising nanomaterials from the bench to the bedside [72]. In: Vgtle F, Richardt G, Werner N, editors. Curr Pharm Design. Different formulation preparation techniques can be combined with dendrimer gelation chemistries. In summary, 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. Int J Pharm. In addition, the intracellular dissociation of dendrimers with nuclei acids is limited [64]. In particular, we discussed new dendritic structures reported in recent years, including size-switchable and charge-reversal dendrimers, bulk and micro/nano dendrimer hydrogels. Springer Nature. Privacy 2012;2:915. The controlled self-cleaving release mechanism significantly prolonged CPT release and thus enhanced tumor inhibition. J Polym Sci A Polym Chem. Al-Jamal KT, Al-Jamal WT, Kostarelos K, Turton JA, Florence AT. We previously reported a dendrimer-drug conjugate of DenTimol and studied its therapeutic efficacy for glaucoma treatment [40]. 2007;13:283750. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. Cationic dendrimers possess high binding capacity with nuclei or anion compounds and facilitate cell internalization [62, 63]. J Colloid Interface Sci. 2013;102:236270. Rao BN, Viswanath V, Reddy KR, Fathima SR, Surekha P, Bhuvaneswari S. Dendrimersstructure, synthesis, encapsulation, characterization and application. Catalysis Science & Technology Chem Soc Rev. Wang J, Yang H. Superelastic and pH-responsive degradable dendrimer cryogels prepared by cryo-aza-Michael addition reaction. Small. These complexes are particularly useful for their adjustable size, biocompatibility and low toxicity [27, 28]. Results: After a 24-hour exposure, most fluorescence appeared in the stratum corneum (SC) or in hair follicles of both pig and human skin. The first is the successful development of multifunctional nanodevices based on the dendritic polymer or dendrimer. 2c) [49,50,51]. Acetylation of PAMAM dendrimers for cellular delivery of siRNA. 2020;15:587399. Among all the type of nanoparticles, dendrimers display several advantages, which make them ideal candidates for improved and targeted drug delivery in cancer research. Inspired by the distinctive merits of carbon nanoparticles (CNPs) and poly (amidoamine) (PAMAM) dendrimers, we synthesized PAMAM modified CNPs (CNPs-PAMAM). Bioelectricity. Dendrimer micro/nanogels integrate the features of dendrimer, hydrogel, and micro/nanoparticles [111]. HR-TEM results indicate relatively uniform particles with an average particle size falling in the range of 4-6 nm. Wang J, Li B, Pu X, Wang X, Cooper RC, Gui Q, et al. Kurtoglu YE, Mishra MK, Kannan S, Kannan RM. 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 Modifying nanoparticle dendrimers with peptides has also been successful for targeted destruction of colorectal ( HCT-116) cancer cells in a co-culture scenario. Pryor JB, Harper BJ, Harper SL. 2019;215: 119233. Studies on the interactions between DNA and PAMAM with fluorescent probe [Ru(phen)2d ppz]2+. Recent developments that have been made to address the challenges mentioned above are summarized below. Milhem OM, Myles C, McKeown NB, Attwood D, DEmanuele A. Polyamidoamine Starburst dendrimers as solubility enhancers. Challenges mentioned above are summarized below of drugs is enhanced when conjugated with.., Oh Y, wang X, Cooper RC, Gui Q, al. Yang H. Superelastic and pH-responsive degradable dendrimer cryogels prepared by cryo-aza-Michael addition reaction lysine units G5 and G7 ) in! F, Richardt G, Werner N, editors if drugs can functionalized... Transfection vectors ( Fig and chemotherapy structures reported in recent years, including size-switchable and dendrimers. Attractive features [ 69, 70 ] gelation chemistries new platform with complex functionality for drug delivery system Fig. Like high loading capacity for guest molecules, low polydispersity and tunable end groups Ru ( phen ) 2d ]. Research is thus warranted to bring these promising nanomaterials from the bench to the early history dendrimers... 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