Designing dendrimers for biological applications

Dendrimers are branched, synthetic polymers with layered architectures that show promise in several biomedical applications. By regulating dendrimer synthesis, it is possible to precisely manipulate both their molecular weight and chemical composition, thereby allowing predictable tuning of their biocompatibility and pharmacokinetics. Advances in our understanding of the role of molecular weight and architecture on the in vivo behavior of dendrimers, together with recent progress in the design of biodegradable chemistries, has enabled the application of these branched polymers as anti-viral drugs, tissue repair scaffolds, targeted carriers of chemotherapeutics and optical oxygen sensors. Before such products can reach the market, however, the field must not only address the cost of manufacture and quality control of pharmaceutical-grade materials, but also assess the long-term human and environmental health consequences of dendrimer exposure in vivo.

[1]  James R. Dewald,et al.  A New Class of Polymers: Starburst-Dendritic Macromolecules , 1985 .

[2]  Elizabeth R Gillies,et al.  Designing macromolecules for therapeutic applications: polyester dendrimer-poly(ethylene oxide) "bow-tie" hybrids with tunable molecular weight and architecture. , 2002, Journal of the American Chemical Society.

[3]  Mark W Grinstaff,et al.  Dendritic molecular capsules for hydrophobic compounds. , 2003, Journal of the American Chemical Society.

[4]  T. Schöneberg,et al.  A surface-modified dendrimer set for potential application as drug delivery vehicles: synthesis, in vitro toxicity, and intracellular localization. , 2004, Chemistry.

[5]  R. Haag,et al.  Dendritic polymers in biomedical applications: from potential to clinical use in diagnostics and therapy. , 2002, Angewandte Chemie.

[6]  M. Jan,et al.  Mechanism of cell death induced by cationic dendrimers in RAW 264.7 murine macrophage‐like cells , 2005, The Journal of pharmacy and pharmacology.

[7]  Sergei A Vinogradov,et al.  Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. , 2002, Analytical biochemistry.

[8]  E. Simanek,et al.  Cytotoxicity, hemolysis, and acute in vivo toxicity of dendrimers based on melamine, candidate vehicles for drug delivery. , 2004, Journal of the American Chemical Society.

[9]  K. Janda,et al.  Synthesis and catalytic antibody functionalization of dendrimers. , 2001, Journal of the American Chemical Society.

[10]  F. Szoka,et al.  In vitro and in vivo evaluation of hydrophilic dendronized linear polymers. , 2005, Bioconjugate chemistry.

[11]  Mark W Grinstaff,et al.  Biodendrimers: new polymeric biomaterials for tissue engineering. , 2002, Chemistry.

[12]  Anders Hult,et al.  Synthesis, Characterization, and 1H NMR Self-Diffusion Studies of Dendritic Aliphatic Polyesters Based on 2,2-Bis(hydroxymethyl)propionic Acid and 1,1,1-Tris(hydroxyphenyl)ethane , 1996 .

[13]  Brigitte Voit,et al.  New developments in hyperbranched polymers , 2000 .

[14]  D. Papahadjopoulos,et al.  Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. , 1999, Pharmacological reviews.

[15]  F. Szoka,et al.  In vitro gene delivery by degraded polyamidoamine dendrimers. , 1996, Bioconjugate chemistry.

[16]  George M Whitesides,et al.  Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors. , 1998, Angewandte Chemie.

[17]  J. Tam,et al.  Peptide dendrimers: applications and synthesis. , 2002, Journal of biotechnology.

[18]  Roey J. Amir,et al.  Self-immolative dendrimers. , 2003, Angewandte Chemie.

[19]  Jean M. J. Fréchet,et al.  Unsymmetrical three-dimensional macromolecules: preparation and characterization of strongly dipolar dendritic macromolecules , 1993 .

[20]  Seungpyo Hong,et al.  Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport. , 2004, Bioconjugate chemistry.

[21]  Terry Kim,et al.  New dendritic adhesives for sutureless ophthalmic surgical procedures: in vitro studies of corneal laceration repair. , 2004, Archives of ophthalmology.

[22]  F. Veronese,et al.  PEG-epirubicin Conjugates with High Drug Loading , 2005 .

[23]  S. Hecht,et al.  Dendritic Encapsulation of Function: Applying Nature′s Site Isolation Principle from Biomimetics to Materials Science , 2001 .

[24]  Xiaojun Cao,et al.  A NEW CONVERGENT APPROACH TO DENDRITIC MACROMOLECULES , 2002 .

[25]  D. McGrath,et al.  Geometric disassembly of dendrimers: dendritic amplification. , 2003, Journal of the American Chemical Society.

[26]  M. Royzen,et al.  Anticancer drug delivery systems: multi-loaded N4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[27]  E. W. Meijer,et al.  Poly(propylene imine) Dendrimers: Large‐Scale Synthesis by Hetereogeneously Catalyzed Hydrogenations , 1993 .

[28]  H. W. Scheeren,et al.  "Cascade-release dendrimers" liberate all end groups upon a single triggering event in the dendritic core. , 2003, Angewandte Chemie.

[29]  R. Roy,et al.  Glycodendrimers: novel glycotope isosteres unmasking sugar coding. case study with T-antigen markers from breast cancer MUC1 glycoprotein. , 2002, Journal of biotechnology.

[30]  Manouchehr Mirshahi,et al.  Efficacy of dendrimer‐mediated angiostatin and TIMP‐2 gene delivery on inhibition of tumor growth and angiogenesis: In vitro and in vivo studies , 2003, International journal of cancer.

[31]  N. McKeown,et al.  The influence of surface modification on the cytotoxicity of PAMAM dendrimers. , 2003, International journal of pharmaceutics.

[32]  Mary J Cloninger,et al.  Biological applications of dendrimers. , 2002, Current opinion in chemical biology.

[33]  P. McEuen,et al.  Controlled assembly of dendrimer-like DNA , 2004, Nature materials.

[34]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[35]  D. Bernstein,et al.  Dendrimers, a New Class of Candidate Topical Microbicides with Activity against Herpes Simplex Virus Infection , 2000, Antimicrobial Agents and Chemotherapy.

[36]  Sergei A Vinogradov,et al.  Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna. , 2005, Journal of the American Chemical Society.

[37]  W. Prensky,et al.  Dendritic nucleic acid structures. , 1997, Journal of theoretical biology.

[38]  H. Gabius,et al.  First demonstration of differential inhibition of lectin binding by synthetic tri- and tetravalent glycoclusters from cross-coupling of rigidified 2-propynyl lactoside. , 2003, Organic & biomolecular chemistry.

[39]  F. Szoka,et al.  Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. , 1993, Bioconjugate chemistry.

[40]  Yonghou Jiang,et al.  SPL7013 gel as a topical microbicide for prevention of vaginal transmission of SHIV89.6P in macaques. , 2005, AIDS research and human retroviruses.

[41]  A. Pini,et al.  Synthetic Peptides in the Form of Dendrimers Become Resistant to Protease Activity* , 2003, Journal of Biological Chemistry.

[42]  K. Kono,et al.  Synthesis of polyamidoamine dendrimers having poly(ethylene glycol) grafts and their ability to encapsulate anticancer drugs. , 2000, Bioconjugate chemistry.

[43]  D. Seebach,et al.  Synthesis and Enzymatic Degradation of Dendrimers from (R)‐3‐Hydroxybutanoic Acid and Trimesic Acid , 1996 .

[44]  J. Fréchet,et al.  Synthesis of narrow-polydispersity degradable dendronized aliphatic polyesters , 2004 .

[45]  P. Trail,et al.  Monoclonal antibody conjugates of doxorubicin prepared with branched peptide linkers: inhibition of aggregation by methoxytriethyleneglycol chains. , 2002, Journal of medicinal chemistry.

[46]  J. Fréchet,et al.  Dendrimers and dendritic polymers in drug delivery. , 2005, Drug discovery today.

[47]  Jean M. J. Fréchet,et al.  Dendrimers and other dendritic polymers , 2001 .

[48]  Y. Ikada,et al.  Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. , 1994, Journal of pharmaceutical sciences.

[49]  E. Toone,et al.  The cluster glycoside effect. , 2002, Chemical reviews.

[50]  Duncan,et al.  Polymer conjugates for tumour targeting and intracytoplasmic delivery. The EPR effect as a common gateway? , 1999, Pharmaceutical science & technology today.

[51]  R. Duncan The dawning era of polymer therapeutics , 2003, Nature Reviews Drug Discovery.

[52]  J. V. Hest,et al.  Synthesis, characterization, and guest-host properties of inverted unimolecular dendritic micelles , 1996 .

[53]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[54]  Francis C Szoka,et al.  Polyester dendritic systems for drug delivery applications: in vitro and in vivo evaluation. , 2002, Bioconjugate chemistry.

[55]  F. Rypáček,et al.  Soluble synthetic polymers in biological systems , 1984 .

[56]  D. Ho,et al.  Macromolecular assemblage in the design of a synthetic AIDS vaccine. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[57]  E. Simanek,et al.  Synthesis and manipulation of orthogonally protected dendrimers: building blocks for library synthesis. , 2004, Angewandte Chemie.

[58]  Liao,et al.  Photolabile dendrimers using o-nitrobenzyl ether linkages , 2000, Organic letters.

[59]  R. Lerner,et al.  Single-triggered trimeric prodrugs. , 2005, Angewandte Chemie.

[60]  A. Blom,et al.  Effects of filtration rate on the glomerular barrier and clearance of four differently shaped molecules. , 2001, American journal of physiology. Renal physiology.

[61]  R. Duncan,et al.  Dendrimer-platinate: a novel approach to cancer chemotherapy. , 1999, Anti-cancer drugs.

[62]  George R. Newkome,et al.  Micelles. Part 1. Cascade molecules: a new approach to micelles. A [27]-arborol , 1985 .

[63]  K. Kono,et al.  Water-soluble dendritic unimolecular micelles: their potential as drug delivery agents. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[64]  E. W. Meijer,et al.  Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[65]  H. Frey,et al.  Controlling the growth of polymer trees: concepts and perspectives for hyperbranched polymers. , 2000, Chemistry.

[66]  J. Rabe,et al.  Molecular structure of single DNA complexes with positively charged dendronized polymers. , 2002, Journal of the American Chemical Society.

[67]  D. McGrath,et al.  Dendrimer disassembly by benzyl ether depolymerization. , 2003, Journal of the American Chemical Society.

[68]  William A. Goddard,et al.  Starburst Dendrimers: Molecular‐Level Control of Size, Shape, Surface Chemistry, Topology, and Flexibility from Atoms to Macroscopic Matter , 1990 .

[69]  David H. Thompson,et al.  Phototriggering of liposomal drug delivery systems. , 2001, Advanced drug delivery reviews.

[70]  E. Simanek,et al.  In vitro and in vivo evaluation of a melamine dendrimer as a vehicle for drug delivery. , 2004, International journal of pharmaceutics.

[71]  Francis C Szoka,et al.  Biological evaluation of polyester dendrimer: poly(ethylene oxide) "bow-tie" hybrids with tunable molecular weight and architecture. , 2005, Molecular pharmaceutics.

[72]  Dan Luo,et al.  Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes , 2005, Nature Biotechnology.

[73]  J Fraser Stoddart,et al.  Design and synthesis of glycodendrimers. , 2002, Journal of biotechnology.

[74]  M. Brechbiel,et al.  Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application , 2003, Molecular imaging.

[75]  G. Maria,et al.  Evaluation of multivalent dendrimers based on melamine: kinetics of thiol-disulfide exchange depends on the structure of the dendrimer. , 2003, Journal of the American Chemical Society.

[76]  Thommey P. Thomas,et al.  Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. , 2005, Cancer research.

[77]  C. Hawker,et al.  Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules , 1990 .

[78]  M. Hashida,et al.  Pharmacokinetic evaluation of polymeric carriers , 1996 .

[79]  F. Szoka,et al.  Polyester dendritic systems for drug delivery applications: design, synthesis, and characterization. , 2002, Bioconjugate chemistry.

[80]  E. Southern,et al.  A novel anionic dendrimer for improved cellular delivery of antisense oligonucleotides. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[81]  J. B. Jones,et al.  Glycodendriproteins: a synthetic glycoprotein mimic enzyme with branched sugar-display potently inhibits bacterial aggregation. , 2004, Journal of the American Chemical Society.

[82]  P. Sontum,et al.  Gadolinium(III) DO3A macrocycles and polyethylene glycol coupled to dendrimers : Effect of molecular weight on physical and biological properties of macromolecular magnetic resonance imaging contrast agents , 1997 .

[83]  C R Robertson,et al.  Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall , 1979, The Journal of general physiology.

[84]  George R. Newkome,et al.  MICELLES. PART 1. CASCADE MOLECULES: A NEW APPROACH TO MICELLES. A (27)-ARBOROL , 1985 .

[85]  E. Buhleier,et al.  "Cascade"- and "Nonskid-Chain-like" Syntheses of Molecular Cavity Topologies , 1978 .

[86]  Sergei A. Vinogradov,et al.  Phosphorescent Pd Porphyrin−Dendrimers: Tuning Core Accessibility by Varying the Hydrophobicity of the Dendritic Matrix , 2002 .

[87]  J. Fréchet,et al.  Dendrimers and Other Dendritic Polymers: Frechet/Dendrimers , 2001 .

[88]  Terry Kim,et al.  Dendritic macromers as in situ polymerizing biomaterials for securing cataract incisions. , 2004, Journal of the American Chemical Society.

[89]  P. Heegaard,et al.  Dendrimers in drug research. , 2004, Chemical Society reviews.

[90]  F. Cohen,et al.  Elimination of prions by branched polyamines and implications for therapeutics. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[91]  P C Lauterbur,et al.  Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents , 1994, Magnetic resonance in medicine.

[92]  Rabe,et al.  Dendronized Polymers: Synthesis, Characterization, Assembly at Interfaces, and Manipulation. , 2000, Angewandte Chemie.

[93]  J. C. Roberts,et al.  Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers. , 1996, Journal of biomedical materials research.

[94]  Sergei A Vinogradov,et al.  Oxygen distribution in murine tumors: characterization using oxygen-dependent quenching of phosphorescence. , 2005, Journal of applied physiology.