Pharmaceutical Biotechnology, Center for System-based Drug Research, and Center for NanoScience, Ludwig-Maximilians-Universit?t Munich, Butenandtstrasse 5-13, D-81377 Munich, Germany
Polymer-based conjugates are an interesting option and challenge for the design of nano-sized drug-delivery systems, as they require advanced conjugation chemistry and precise engineering. In the case of nucleic acid therapy, non-viral carriers face several biological barriers during the delivery process, namely 1) protection of the cargo from extracellular degradation, 2) avoidance of non-specific interactions with non-targeted tissues, 3) efficient entry into the target cells, 4) intracellular trafficking to the site of action and 5) cargo release. To take on these obstacles, multifunctional conjugates can act as “smart polymers” with microenvironment-sensing dynamics to facilitate the separate delivery steps. Synthesis of defined polymer architectures with precise functionalization enables structure-activity relationships to be investigated and the integration of key functions for efficient delivery. Thus bioresponsive polymer conjugates, which are equipped with molecular devices responding to the certain microenvironments within the delivery pathway (e.g. pH, redox potential, enzymes) can be assembled. This review focuses on the modular engineering and conjugation of multifunctional polymeric structures for the utilization as “tailor-made” nucleic acid carriers.
Famulok M, Ackermann D. RNA nanotechnology: inspired by DNA. Nature Nanotechnology , 2010, 5(9): 634–635 doi: 10.1038/nnano.2010.183
2
Guo P. The emerging field of RNA nanotechnology. Nature Nanotechnology , 2010, 5(12): 833–842 doi: 10.1038/nnano.2010.231
3
Shir A, Ogris M, Wagner E, Levitzki A. EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice. PLoS Medicine , 2006, 3(1): e6 doi: 10.1371/journal.pmed.0030006
4
Schaffert D, Kiss M, R?dl W, Shir A, Levitzki A, Ogris M, Wagner E. Poly(I:C)-mediated tumor growth suppression in EGF-receptor overexpressing tumors using EGF-polyethylene glycol-linear polyethylenimine as carrier. Pharmaceutical Research , 2011, 28(4): 731–741 doi: 10.1007/s11095-010-0225-4
5
Shir A, Ogris M, Roedl W, Wagner E, Levitzki A. EGFR-homing dsRNA activates cancer-targeted immune response and eliminates disseminated EGFR-overexpressing tumors in mice. Clinical Cancer Research , 2011, 17(5): 1033–1043 doi: 10.1158/1078-0432.CCR-10-1140
6
Venkataraman S, Dirks R M, Ueda C T, Pierce N A. Selective cell death mediated by small conditional RNAs. Proceedings of the National Academy of Sciences of the United States of America , 2010, 107(39): 16777–16782 doi: 10.1073/pnas.1006377107
7
Ulrich H, Trujillo C A, Nery A A, Alves J M, Majumder P, Resende R R, Martins A H. DNA and RNA aptamers: from tools for basic research towards therapeutic applications. Combinatorial Chemistry & High Throughput Screening , 2006, 9(8): 619–632 doi: 10.2174/138620706778249695
8
Gutsaeva D R, Parkerson J B, Yerigenahally S D, Kurz J C, Schaub R G, Ikuta T, Head C A. Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood , 2011, 117(2): 727–735 doi: 10.1182/blood-2010-05-285718
9
Sassanfar M, Szostak J W. An RNA motif that binds ATP. Nature , 1993, 364(6437): 550–553 doi: 10.1038/364550a0
10
Ellington A D, Szostak J W. In vitro selection of RNA molecules that bind specific ligands. Nature , 1990, 346(6287): 818–822 doi: 10.1038/346818a0
11
Maasch C, Vater A, Buchner K, Purschke W G, Eulberg D, Vonhoff S, Klussmann S. Polyetheylenimine-polyplexes of Spiegelmer NOX-A50 directed against intracellular high mobility group protein A1 (HMGA1) reduce tumor growth in vivo. The Journal of Biological Chemistry , 2010, 285(51): 40012–40018 doi: 10.1074/jbc.M110.178533
12
Dua P, Kim S, Lee D K. Nucleic acid aptamers targeting cell-surface proteins. Methods (San Diego, Calif.) , 2011 doi: 10.1016/j.ymeth.2011.02.002
13
Keefe A D, Pai S, Ellington A. Aptamers as therapeutics. Nature Reviews. Drug Discovery , 2010, 9(7): 537–550 doi: 10.1038/nrd3141
14
Li S D, Huang L. Non-viral is superior to viral gene delivery. Journal of Controlled Release: Official Journal of the Controlled Release Society , 2007, 123(3): 181–183
15
Tamura A, Nagasaki Y. Smart siRNA delivery systems based on polymeric nanoassemblies and nanoparticles. Nanomedicine (Lond) , 2010, 5(7): 1089–1102 doi: 10.2217/nnm.10.76
16
Mansouri S, Lavigne P, Corsi K, Benderdour M, Beaumont E, Fernandes J C. Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy. European Journal of Pharmaceutics and Biopharmaceutics: Official Journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V , 2004, 57(1): 1–8
17
Behr J P. The proton sponge: A trick to enter cells the viruses did not exploit. Chimia , 1997, 51(1–2): 34–36
18
Kichler A, Leborgne C, Coeytaux E, Danos O. Polyethylenimine-mediated gene delivery: a mechanistic study. The Journal of Gene Medicine , 2001, 3(2): 135–144 doi: 10.1002/jgm.173
19
von Harpe A, Petersen H, Li Y, Kissel T. Characterization of commercially available and synthesized polyethylenimines for gene delivery. Journal of Controlled Release : Official Journal of the Controlled Release Society , 2000, 69(2): 309–322
20
Werth S, Urban-Klein B, Dai L, H?bel S, Grzelinski M, Bakowsky U, Czubayko F, Aigner A. A low molecular weight fraction of polyethylenimine (PEI) displays increased transfection efficiency of DNA and siRNA in fresh or lyophilized complexes. Journal of Controlled Release: Official Journal of the Controlled Release Society , 2006, 112(2): 257–270
21
Cherng J Y, van de Wetering P, Talsma H, Crommelin D J A, Hennink W E. Effect of size and serum proteins on transfection efficiency of poly ((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles. Pharmaceutical Research , 1996, 13(7): 1038–1042 doi: 10.1023/A:1016054623543
22
van de Wetering P, Cherng J Y, Talsma H, Hennink W E. Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl methacrylate)/plasmid complexes. Journal of Controlled Release , 1997, 49(1): 59–69 doi: 10.1016/S0168-3659(97)00059-X
23
van de Wetering P, Cherng J Y, Talsma H, Crommelin D J, Hennink W E. 2-(Dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents. Journal of Controlled Release: Official Journal of the Controlled Release Society , 1998, 53(1–3): 145–153
24
Xu F J, Li H, Li J, Zhang Z, Kang E T, Neoh K G. Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery. Biomaterials , 2008, 29(20): 3023–3033 doi: 10.1016/j.biomaterials.2008.03.041
25
Kr?mer M, Stumbé J F, Grimm G, Kaufmann B, Krüger U, Weber M, Haag R. Dendritic polyamines: simple access to new materials with defined treelike structures for application in nonviral gene delivery. Chembiochem : a European Journal of Chemical Biology , 2004, 5(8): 1081–1087
26
Esfand R, Tomalia D A. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discovery Today , 2001, 6(8): 427–436 doi: 10.1016/S1359-6446(01)01757-3
27
Hartmann L. Polymers for control freaks: sequence-defined poly(amidoamine)s and their biomedical applications. Macromolecular Chemistry and Physics , 2011, 212(1): 8–13 doi: 10.1002/macp.201000479
28
Hartmann L, Krause E, Antonietti M, B?rner H G. Solid-phase supported polymer synthesis of sequence-defined, multifunctional poly(amidoamines). Biomacromolecules , 2006, 7(4): 1239–1244 doi: 10.1021/bm050884k
29
Hartmann L, H?fele S, Peschka-Süss R, Antonietti M, B?rner H G. Tailor-made poly(amidoamine)s for controlled complexation and condensation of DNA. Chemistry , 2008, 14(7): 2025–2033 doi: 10.1002/chem.200701223
30
Schaffert D, Badgujar N, Wagner E. Novel Fmoc-polyamino acids for solid-phase synthesis of defined polyamidoamines. Organic Letters , 2011, 13(7): 1586–1589 doi: 10.1021/ol200381z
31
Burke R S, Pun S H. Extracellular barriers to in vivo PEI and PEGylated PEI polyplex-mediated gene delivery to the liver. Bioconjugate Chemistry , 2008, 19(3): 693–704 doi: 10.1021/bc700388u
32
Edinger D, Wagner E. Bioresponsive polymers for the delivery of therapeutic nucleic acids. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology , 2011, 3(1): 33–46 doi: 10.1002/wnan.97
33
Itaka K, Harada A, Yamasaki Y, Nakamura K, Kawaguchi H, Kataoka K. In situ single cell observation by fluorescence resonance energy transfer reveals fast intra-cytoplasmic delivery and easy release of plasmid DNA complexed with linear polyethylenimine. The Journal of Gene Medicine , 2004, 6(1): 76–84 doi: 10.1002/jgm.470
34
Oupicky D, Parker A L, Seymour L W. Laterally stabilized complexes of DNA with linear reducible polycations: strategy for triggered intracellular activation of DNA delivery vectors. Journal of the American Chemical Society , 2002, 124(1): 8–9 doi: 10.1021/ja016440n
35
Neu M, Germershaus O, Mao S, Voigt K H, Behe M, Kissel T. Crosslinked nanocarriers based upon poly(ethylene imine) for systemic plasmid delivery: in vitro characterization and in vivo studies in mice. Journal of Controlled Release: Official Journal of the Controlled Release Society , 2007, 118(3): 370–380
36
Miyata K, Kakizawa Y, Nishiyama N, Harada A, Yamasaki Y, Koyama H, Kataoka K. Block catiomer polyplexes with regulated densities of charge and disulfide cross-linking directed to enhance gene expression. Journal of the American Chemical Society , 2004, 126(8): 2355–2361 doi: 10.1021/ja0379666
37
Russ V, Fr?hlich T, Li Y, Halama A, Ogris M, Wagner E. Improved in vivo gene transfer into tumor tissue by stabilization of pseudodendritic oligoethylenimine-based polyplexes. The journal of gene medicine , 2010, 12(2): 180–193
38
Hamidi M, Azadi A, Rafiei P. Pharmacokinetic consequences of pegylation. Drug Delivery , 2006, 13(6): 399–409 doi: 10.1080/10717540600814402
39
Itaka K, Yamauchi K, Harada A, Nakamura K, Kawaguchi H, Kataoka K. Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer as serum-tolerable polyplex system: physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials , 2003, 24(24): 4495–4506 doi: 10.1016/S0142-9612(03)00347-8
40
Venkataraman S, Ong W L, Ong Z Y, Joachim Loo S C, Ee P L, Yang Y Y. The role of PEG architecture and molecular weight in the gene transfection performance of PEGylated poly(dimethylaminoethyl methacrylate) based cationicβpolymers. Biomaterials , 2011, 32(9): 2369–2378 doi: 10.1016/j.biomaterials.2010.11.070
41
Lai T C, Bae Y, Yoshida T, Kataoka K, Kwon G S. pH-sensitive multi-PEGylated block copolymer as a bioresponsive pDNA delivery vector. Pharmaceutical Research , 2010, 27(11): 2260–2273 doi: 10.1007/s11095-010-0092-z
42
Tamura A, Oishi M, Nagasaki Y. Enhanced cytoplasmic delivery of siRNA using a stabilized polyion complex based on PEGylated nanogels with a cross-linked polyamine structure. Biomacromolecules , 2009, 10(7): 1818–1827 doi: 10.1021/bm900252d
43
Meyer M, Dohmen C, Philipp A, Kiener D, Maiwald G, Scheu C, Ogris M, Wagner E. Synthesis and biological evaluation of a bioresponsive and endosomolytic siRNA-polymer conjugate. Molecular Pharmaceutics , 2009, 6(3): 752–762 doi: 10.1021/mp9000124
44
Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, Yamasaki Y, Koyama H, Kataoka K. PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. Journal of the American Chemical Society , 2008, 130(18): 6001–6009 doi: 10.1021/ja800336v
45
Hatakeyama H, Akita H, Harashima H. A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Advanced Drug Delivery Reviews , 2011, 63(3): 152–160 doi: 10.1016/j.addr.2010.09.001
46
Dash P R, Read M L, Fisher K D, Howard K A, Wolfert M, Oupicky D, Subr V, Strohalm J, Ulbrich K, Seymour L W. Decreased binding to proteins and cells of polymeric gene delivery vectors surface modified with a multivalent hydrophilic polymer and retargeting through attachment of transferrin.The Journal of Biological Chemistry , 2000, 275(6): 3793–3802 doi: 10.1074/jbc.275.6.3793
47
Oupicky D, Ogris M, Howard K A, Dash P R, Ulbrich K, Seymour L W. Importance of lateral and steric stabilization of polyelectrolyte gene delivery vectors for extended systemic circulation. Molecular Therapy: the Journal of the American Society of Gene Therapy , 2002, 5(4): 463–472
48
Ito T, Yoshihara C, Hamada K, Koyama Y. DNA/polyethyleneimine/hyaluronic acid small complex particles and tumor suppression in mice. Biomaterials , 2010, 31(10): 2912–2918 doi: 10.1016/j.biomaterials.2009.12.032
49
Hornof M, de la Fuente M, Hallikainen M, Tammi R H, Urtti A. Low molecular weight hyaluronan shielding of DNA/PEI polyplexes facilitates CD44 receptor mediated uptake in human corneal epithelial cells. The Journal of Gene Medicine , 2008, 10(1): 70–80 doi: 10.1002/jgm.1125
50
Kircheis R, Wightman L, Schreiber A, Robitza B, R?ssler V, Kursa M, Wagner E. Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application. Gene Therapy , 2001, 8(1): 28–40 doi: 10.1038/sj.gt.3301351
Li S D, Chono S, Huang L. Efficient oncogene silencing and metastasis inhibition via systemic delivery of siRNA. Molecular Therapy , 2008, 16(5): 942–946 doi: 10.1038/mt.2008.51
53
Li S D, Huang L. Surface-modified LPD nanoparticles for tumor targeting. Annals of the New York Academy of Sciences , 2006, 1082(1): 1–8 doi: 10.1196/annals.1348.001
54
Hong M S, Lim S J, Oh Y K, Kim C K. pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery system. Journal of Pharmacy and Pharmacology , 2002, 54(1): 51–58 doi: 10.1211/0022357021771913
55
Miller C R, Bondurant B, McLean S D, McGovern K A, O’Brien D F. Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. Biochemistry , 1998, 37(37): 12875–12883 doi: 10.1021/bi980096y
56
O’Riordan C R, Lachapelle A, Delgado C, Parkes V, Wadsworth S C, Smith A E, Francis G E. PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo. Human Gene Therapy , 1999, 10(8): 1349–1358 doi: 10.1089/10430349950018021
57
Croyle M A, Yu Q C, Wilson J M. Development of a rapid method for the PEGylation of adenoviruses with enhanced transduction and improved stability under harsh storage conditions. Human Gene Therapy , 2000, 11(12): 1713–1722 doi: 10.1089/10430340050111368
58
Wolfert M A, Schacht E H, Toncheva V, Ulbrich K, Nazarova O, Seymour L W. Characterization of vectors for gene therapy formed by self-assembly of DNA with synthetic block co-polymers. Human Gene Therapy , 1996, 7(17): 2123–2133 doi: 10.1089/hum.1996.7.17-2123
59
Erbacher P, Bettinger T, Belguise-Valladier P, Zou S, Coll J L, Behr J P, Remy J S. Transfection and physical properties of various saccharide, poly(ethylene glycol), and antibody-derivatized polyethylenimines (PEI). Journal of Gene Medicine , 1999, 1(3): 210–222 doi: 10.1002/(SICI)1521-2254(199905/06)1:3<210::AID-JGM30>3.0.CO;2-U
60
Kursa M, Walker G F, Roessler V, Ogris M, Roedl W, Kircheis R, Wagner E. Novel shielded transferrin-polyethylene glycol-polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer. Bioconjugate Chemistry , 2003, 14(1): 222–231 doi: 10.1021/bc0256087
61
Kasper J C, Schaffert D, Ogris M, Wagner E, Friess W. Development of a lyophilized plasmid/LPEI polyplex formulation with long-term stability–A step closer from promising technology to application. Journal of Controlled Release , 2011, 151(3): 246–255 doi: 10.1016/j.jconrel.2011.01.003
62
Kasper J C, Schaffert D, Ogris M, Wagner E, Friess W. The establishment of an up-scaled micro-mixer method allows the standardized and reproducible preparation of well-defined plasmid/LPEI polyplexes. European Journal of Pharmaceutics and Biopharmaceutics , 2011, 77(1): 182–185 doi: 10.1016/j.ejpb.2010.11.012
63
Zhang X, Pan S R, Hu H M, Wu G F, Feng M, Zhang W, Luo X. Poly(ethylene glycol)-block-polyethylenimine copolymers as carriers for gene delivery: effects of PEG molecular weight and PEGylation degree. Journal of Biomedical Materials Research. Part A , 2008, 84A(3): 795–804 doi: 10.1002/jbm.a.31343
64
Walker G F, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, Wagner E. Toward synthetic viruses: endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. Molecular Therapy , 2005, 11(3): 418–425 doi: 10.1016/j.ymthe.2004.11.006
65
Fella C, Walker G F, Ogris M, Wagner E. Amine-reactive pyridylhydrazone-based PEG reagents for pH-reversible PEI polyplex shielding. European Journal of Pharmaceutical Sciences , 2008, 34(4–5): 309–320 doi: 10.1016/j.ejps.2008.05.004
66
Knorr V, Ogris M, Wagner E. An acid sensitive ketal-based polyethylene glycol-oligoethylenimine copolymer mediates improved transfection efficiency at reduced toxicity. Pharmaceutical Research , 2008, 25(12): 2937–2945 doi: 10.1007/s11095-008-9700-6
67
Knorr V, Allmendinger L, Walker G F, Paintner F F, Wagner E. An acetal-based PEGylation reagent for pH-sensitive shielding of DNA polyplexes. Bioconjugate Chemistry , 2007, 18(4): 1218–1225 doi: 10.1021/bc060327a
68
Li W, Huang Z, MacKay J A, Grube S, Szoka F C Jr. Low-pH-sensitive poly(ethylene glycol) (PEG)-stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery. The Journal of Gene Medicine , 2005, 7(1): 67–79 doi: 10.1002/jgm.634
69
Hatakeyama H, Akita H, Kogure K, Oishi M, Nagasaki Y, Kihira Y, Ueno M, Kobayashi H, Kikuchi H, Harashima H. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Therapy , 2007, 14(1): 68–77 doi: 10.1038/sj.gt.3302843
70
Ikeda Y, Taira K. Ligand-targeted delivery of therapeutic siRNA. Pharmaceutical Research , 2006, 23(8): 1631–1640 doi: 10.1007/s11095-006-9001-x
71
Thurnher M, Wagner E, Clausen H, Mechtler K, Rusconi S, Dinter A, Birnstiel M L, Berger E G, Cotten M. Carbohydrate receptor-mediated gene transfer to human T leukaemic cells. Glycobiology , 1994, 4(4): 429–435 doi: 10.1093/glycob/4.4.429
72
Sp?nkuch B, Steinhauser I, Wartlick H, Kurunci-Csacsko E, Strebhardt K I, Langer K. Downregulation of Plk1 expression by receptor-mediated uptake of antisense oligonucleotide-loaded nanoparticles. Neoplasia (New York, N.Y.) , 2008, 10(3): 223–234
73
Saul J M, Annapragada A V, Bellamkonda R V. A dual-ligand approach for enhancing targeting selectivity of therapeutic nanocarriers. Journal of Controlled Release , 2006, 114(3): 277–287 doi: 10.1016/j.jconrel.2006.05.028
74
Moffatt S, Papasakelariou C, Wiehle S, Cristiano R. Successful in vivo tumor targeting of prostate-specific membrane antigen with a highly efficient J591/PEI/DNA molecular conjugate. Gene Therapy , 2006, 13(9): 761–772 doi: 10.1038/sj.gt.3302721
75
de Bruin K, Ruthardt N, von Gersdorff K, Bausinger R, Wagner E, Ogris M, Br?uchle C. Cellular dynamics of EGF receptor-targeted synthetic viruses. Molecular Therapy , 2007, 15(7): 1297–1305 doi: 10.1038/sj.mt.6300176
76
Wolschek M F, Thallinger C, Kursa M, R?ssler V, Allen M, Lichtenberger C, Kircheis R, Lucas T, Willheim M, Reinisch W, Gangl A, Wagner E, Jansen B. Specific systemic nonviral gene delivery to human hepatocellular carcinoma xenografts in SCID mice. Hepatology (Baltimore, Md.) , 2002, 36(5): 1106–1114 doi: 10.1053/jhep.2002.36372
77
Elfinger M, Pfeifer C, Uezguen S, Golas M M, Sander B, Maucksch C, Stark H, Aneja M K, Rudolph C. Self-assembly of ternary insulin-polyethylenimine (PEI)-DNA nanoparticles for enhanced gene delivery and expression in alveolar epithelial cells. Biomacromolecules , 2009, 10(10): 2912–2920 doi: 10.1021/bm900707j
78
Furgeson D Y, Chan W S, Yockman J W, Kim S W. Modified linear polyethylenimine-cholesterol conjugates for DNA complexation. Bioconjugate Chemistry , 2003, 14(4): 840–847 doi: 10.1021/bc0340565
79
Thomas M, Kularatne S A, Qi L, Kleindl P, Leamon C P, Hansen M J, Low P S. Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues. Annals of the New York Academy of Sciences , 2009, 1175(1): 32–39 doi: 10.1111/j.1749-6632.2009.04977.x
80
Xia W, Low P S. Folate-targeted therapies for cancer. Journal of Medicinal Chemistry , 2010, 53(19): 6811–6824 doi: 10.1021/jm100509v
81
Wang S, Lee R J, Cauchon G, Gorenstein D G, Low P S.Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol. Proc Natl Acad Sci USA , 1995, 92(0027–8424): 3318–3322
82
Kularatne S A, Low P S. Targeting of nanoparticles: folate receptor. Methods in Molecular Biology (Clifton, N.J.) , 2010, 624: 249–265 doi: 10.1007/978-1-60761-609-2_17
83
Zhang K, Wang Q, Xie Y, Mor G, Sega E, Low P S, Huang Y. Receptor-mediated delivery of siRNAs by tethered nucleic acid base-paired interactions. RNA (New York) , 2008, 14(3): 577–583
84
Elfinger M, Geiger J, Hasenpusch G, Uzgün S, Sieverling N, Aneja M K, Maucksch C, Rudolph C. Targeting of the beta(2)-adrenoceptor increases nonviral gene delivery to pulmonary epithelial cells in vitro and lungs in vivo. Journal of Controlled Release , 2009, 135(3): 234–241 doi: 10.1016/j.jconrel.2009.01.012
85
Geiger J, Aneja M K, Hasenpusch G, Yüksekdag G, Kummerl?we G, Luy B, Romer T, Rothbauer U, Rudolph C. Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues. Biomaterials , 2010, 31(10): 2903–2911 doi: 10.1016/j.biomaterials.2009.12.035
86
Li S D, Chen Y C, Hackett M J, Huang L. Tumor-targeted delivery of siRNA by self-assembled nanoparticles. Molecular Therapy , 2008, 16(1): 163–169 doi: 10.1038/sj.mt.6300323
87
Li S D, Huang L. Targeted delivery of antisense oligodeoxynucleotide and small interference RNA into lung cancer cells. Molecular Pharmaceutics , 2006, 3(5): 579–588 doi: 10.1021/mp060039w
88
Oishi M, Kataoka K, Nagasaki Y. pH-responsive three-layered PEGylated polyplex micelle based on a lactosylated ABC triblock copolymer as a targetable and endosome-disruptive nonviral gene vector. Bioconjugate Chemistry , 2006, 17(3): 677–688 doi: 10.1021/bc050364m
89
Oishi M, Nagatsugi F, Sasaki S, Nagasaki Y, Kataoka K. Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotides containing acid-labile linkages. ChemBioChem , 2005, 6(4): 718–725 doi: 10.1002/cbic.200400334
90
Zauner W, Ogris M, Wagner E. Polylysine-based transfection systems utilizing receptor-mediated delivery. Advanced Drug Delivery Reviews , 1998, 30(1–3): 97–113 doi: 10.1016/S0169-409X(97)00110-5
91
Oba M, Fukushima S, Kanayama N, Aoyagi K, Nishiyama N, Koyama H, Kataoka K. Cyclic RGD peptide-conjugated polyplex micelles as a targetable gene delivery system directed to cells possessing alphavbeta3 and alphavbeta5 integrins. Bioconjugate Chemistry , 2007, 18(5): 1415–1423 doi: 10.1021/bc0700133
92
Taratula O, Garbuzenko O B, Kirkpatrick P, Pandya I, Savla R, Pozharov V P, He H, Minko T. Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery. Journal of Controlled Release , 2009, 140(3): 284–293 doi: 10.1016/j.jconrel.2009.06.019
93
Han L, Huang R, Li J, Liu S, Huang S, Jiang C. Plasmid pORF-hTRAIL and doxorubicin co-delivery targeting to tumor using peptide-conjugated polyamidoamine dendrimer. Biomaterials , 2011, 32(4): 1242–1252 doi: 10.1016/j.biomaterials.2010.09.070
94
Klutz K, Schaffert D, Willhauck M J, Grünwald G K, Haase R, Wunderlich N, Zach C, Gildehaus F J, Senekowitsch-Schmidtke R, G?ke B, Wagner E, Ogris M, Spitzweg C. Epidermal growth factor receptor-targeted (131)I-therapy of liver cancer following systemic delivery of the sodium iodide symporter gene. Molecular Therapy , 2011, 19(4): 676–685 doi: 10.1038/mt.2010.296
95
Herbst R S. Review of epidermal growth factor receptor biology. International Journal of Radiation Oncology, Biology, Physics , 2004, 59(2, Suppl): S21–S26 doi: 10.1016/j.ijrobp.2003.11.041
96
Li Z, Zhao R, Wu X, Sun Y, Yao M, Li J, Xu Y, Gu J. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. The FASEB Journal , 2005, 19(14): 1978–1985 doi: 10.1096/fj.05-4058com
97
Leamon C P, Low P S. Folate-mediated targeting: from diagnostics to drug and gene delivery. Drug Discovery Today , 2001, 6(1): 44–51 doi: 10.1016/S1359-6446(00)01594-4
98
Ross J F, Chaudhuri P K, Ratnam M. Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer , 1994, 73(9): 2432–2443 doi: 10.1002/1097-0142(19940501)73:9<2432::AID-CNCR2820730929>3.0.CO;2-S
99
Hwa Kim S, Hoon Jeong J, Chul Cho K, Wan Kim S, Gwan Park T. Target-specific gene silencing by siRNA plasmid DNA complexed with folate-modified poly(ethylenimine). Journal of Controlled Release , 2005, 104(1): 223–232 doi: 10.1016/j.jconrel.2005.02.006
100
Bellocq N C, Pun S H, Jensen G S, Davis M E. Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. Bioconjugate Chemistry , 2003, 14(6): 1122–1132 doi: 10.1021/bc034125f
101
Thorstensen K, Romslo I. The transferrin receptor: its diagnostic value and its potential as therapeutic target. Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum , 1993, 53(s215): 113–120 doi: 10.3109/00365519309090703
102
Gatter K C, Brown G, Trowbridge I S, Woolston R E, Mason D Y. Transferrin receptors in human tissues: their distribution and possible clinical relevance. Journal of Clinical Pathology , 1983, 36(5): 539–545 doi: 10.1136/jcp.36.5.539
103
Davis M E, Zuckerman J E, Choi C H, Seligson D, Tolcher A, Alabi C A, Yen Y, Heidel J D, Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature , 2010, 464(7291): 1067–1070 doi: 10.1038/nature08956
104
Davis M E. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Molecular Pharmaceutics , 2009, 6(3): 659–668 doi: 10.1021/mp900015y
105
Quan C Y, Chang C, Wei H, Chen C S, Xu X D, Cheng S X, Zhang X Z, Zhuo R X. Dual targeting of a thermosensitive nanogel conjugated with transferrin and RGD-containing peptide for effective cell uptake and drug release. Nanotechnology , 2009, 20(33): 335101 doi: 10.1088/0957-4484/20/33/335101
106
Kakimoto S, Moriyama T, Tanabe T, Shinkai S, Nagasaki T. Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery. Journal of Controlled Release , 2007, 120(3): 242–249 doi: 10.1016/j.jconrel.2007.05.001
107
Wagner E, Cotten M, Foisner R, Birnstiel M L. Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proceedings of the National Academy of Sciences of the United States of America , 1991, 88(10): 4255–4259 doi: 10.1073/pnas.88.10.4255
108
Han L, Huang R, Liu S, Huang S, Jiang C. Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors. Molecular Pharmaceutics , 2010, 7(6): 2156–2165 doi: 10.1021/mp100185f
109
Xia H, Anderson B, Mao Q, Davidson B L. Recombinant human adenovirus: targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium. Journal of Virology , 2000, 74(23): 11359–11366 doi: 10.1128/JVI.74.23.11359-11366.2000
110
Li D, Tang G P, Li J Z, Kong Y, Huang H L, Min L J, Zhou J, Shen F P, Wang Q Q, Yu H. Dual-targeting non-viral vector based on polyethylenimine improves gene transfer efficiency. Journal of Biomaterials Science. Polymer Edition , 2007, 18(5): 545–560 doi: 10.1163/156856207780852532
111
Suh W, Han S O, Yu L, Kim S W. An angiogenic, endothelial-cell-targeted polymeric gene carrier. Molecular Therapy , 2002, 6(5): 664–672 doi: 10.1016/S1525-0016(02)90721-5
112
Bai M, Campisi L, Freimuth P. Vitronectin receptor antibodies inhibit infection of HeLa and A549 cells by adenovirus type 12 but not by adenovirus type 2. Journal of Virology , 1994, 68(9): 5925–5932
113
Nie Y, Schaffert D, R?dl W, Ogris M, Wagner E, Günther M. Dual-targeted polyplexes: One step towards a synthetic virus for cancer gene therapy. Journal of Controlled Release , 2011, doi: 10.1016/j.jconrel.2011.02.028 doi: 10.1016/j.jconrel.2011.02.028
114
Wagner E. Effects of membrane-active agents in gene delivery. Journal of Controlled Release , 1998, 53(1–3): 155–158 doi: 10.1016/S0168-3659(97)00249-6
115
Curiel D T, Agarwal S, Wagner E, Cotten M. Adenovirus enhancement of transferrin-polylysine-mediated gene delivery. Proceedings of the National Academy of Sciences of the United States of America , 1991, 88(19): 8850–8854 doi: 10.1073/pnas.88.19.8850
116
Meyer M, Philipp A, Oskuee R, Schmidt C, Wagner E. Breathing life into polycations: functionalization with pH-responsive endosomolytic peptides and polyethylene glycol enables siRNA delivery. Journal of the American Chemical Society , 2008, 130(11): 3272–3273 doi: 10.1021/ja710344v
117
Meyer M, Zintchenko A, Ogris M, Wagner E. A dimethylmaleic acid-melittin-polylysine conjugate with reduced toxicity, pH-triggered endosomolytic activity and enhanced gene transfer potential. The Journal of Gene Medicine , 2007, 9(9): 797–805 doi: 10.1002/jgm.1075
118
Wagner E, Plank C, Zatloukal K, Cotten M, Birnstiel M L. Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle. Proceedings of the National Academy of Sciences of the United States of America , 1992, 89(17): 7934–7938 doi: 10.1073/pnas.89.17.7934
119
Plank C, Zatloukal K, Cotten M, Mechtler K, Wagner E. Gene transfer into hepatocytes using asialoglycoprotein receptor mediated endocytosis of DNA complexed with an artificial tetra-antennary galactose ligand. Bioconjugate Chemistry , 1992, 3(6): 533–539 doi: 10.1021/bc00018a012
120
Roy R, Jerry D J, Thayumanavan S. Virus-inspired approach to nonviral gene delivery vehicles. Biomacromolecules , 2009, 10(8): 2189–2193 doi: 10.1021/bm900370p
121
Wang H, Liu K, Chen K J, Lu Y, Wang S, Lin W Y, Guo F, Kamei K, Chen Y C, Ohashi M, Wang M, Garcia M A, Zhao X Z, Shen C K, Tseng H R. A rapid pathway toward a superb gene delivery system: programming structural and functional diversity into a supramolecular nanoparticle library. ACS Nano , 2010, 4(10): 6235–6243 doi: 10.1021/nn101908e
122
Kleemann E, Neu M, Jekel N, Fink L, Schmehl T, Gessler T, Seeger W, Kissel T. Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. Journal of Controlled Release , 2005, 109(1–3): 299–316 doi: 10.1016/j.jconrel.2005.09.036
123
Pun S H, Bellocq N C, Liu A, Jensen G, Machemer T, Quijano E, Schluep T, Wen S, Engler H, Heidel J, Davis M E. Cyclodextrin-modified polyethylenimine polymers for gene delivery. Bioconjugate Chemistry , 2004, 15(4): 831–840 doi: 10.1021/bc049891g
124
Sletten E M, Bertozzi C R. Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angewandte Chemie (International ed. in English), 2009, 48(38): 6974–6998 doi: 10.1002/anie.200900942
125
Navath R S, Menjoge A R, Wang B, Romero R, Kannan S, Kannan R M. Amino acid-functionalized dendrimers with heterobifunctional chemoselective peripheral groups for drug delivery applications. Biomacromolecules , 2010, 11(6): 1544–1563 doi: 10.1021/bm100186b