Lipid-Nucleic Acid Supramolecular Complexes: Lipoplex Structure and the Kinetics of Formation

Nily Dan; Nily Dan

doi:10.3934/biophy.2015.2.163

AIMS Biophysics

2015, Volume 2, Issue 2: 163-183. doi: 10.3934/biophy.2015.2.163

Previous Article Next Article

Review Special Issues

Lipid-Nucleic Acid Supramolecular Complexes: Lipoplex Structure and the Kinetics of Formation

Nily Dan ^,

Department of Chemical and Biological Engineering, Drexel University, Philadelphia, PA, 19104, USA

Received: 25 April 2015 Accepted: 04 June 2015 Published: 12 June 2015

The need for synthetic gene therapy or gene silencing vehicles that can insert therapeutic nucleic acids (DNA or siRNA) into cells (so-called transfection) has focused interest on lipid-nucleic acid assemblies (lipoplexes). This paper reviews the kinetics pathways leading to lipoplex formation and structure. The process is qualitatively comparable to those of cluster nucleation and growth and to the adsorption of polyelectrolytes on colloidal particles: Initially is a rapid stage where the nucleic acid binds onto the surface of the cationic lipid aggregate (adsorption, or nucleation). This is followed by an intermediate step where the lipid/nucleic acid complexes flocculate to form larger structures (growth). The last and final step involves internal rearrangement, where the overall global structure remains constant while local adjustment of the nucleic acid/lipid organization takes place until the equilibrium lipoplex characteristics are obtained. This step can require unusually long time scales of order hours or longer. Understanding the kinetics of lipoplex formation is not only of fundamental interest as a multi-component, multi-length scale and multi-time scale process, but also has significant implications for the utilization of lipoplexes as carriers for gene delivery and gene silencing agents.
- lipoplexes,
- gene therapy,
- non-viral carriers,
- kinetics,
- DNA/lipid,
- siRNA,
- self-assembly
Citation: Nily Dan. Lipid-Nucleic Acid Supramolecular Complexes: Lipoplex Structure and the Kinetics of Formation[J]. AIMS Biophysics, 2015, 2(2): 163-183. doi: 10.3934/biophy.2015.2.163

Related Papers:

Abstract

The need for synthetic gene therapy or gene silencing vehicles that can insert therapeutic nucleic acids (DNA or siRNA) into cells (so-called transfection) has focused interest on lipid-nucleic acid assemblies (lipoplexes). This paper reviews the kinetics pathways leading to lipoplex formation and structure. The process is qualitatively comparable to those of cluster nucleation and growth and to the adsorption of polyelectrolytes on colloidal particles: Initially is a rapid stage where the nucleic acid binds onto the surface of the cationic lipid aggregate (adsorption, or nucleation). This is followed by an intermediate step where the lipid/nucleic acid complexes flocculate to form larger structures (growth). The last and final step involves internal rearrangement, where the overall global structure remains constant while local adjustment of the nucleic acid/lipid organization takes place until the equilibrium lipoplex characteristics are obtained. This step can require unusually long time scales of order hours or longer. Understanding the kinetics of lipoplex formation is not only of fundamental interest as a multi-component, multi-length scale and multi-time scale process, but also has significant implications for the utilization of lipoplexes as carriers for gene delivery and gene silencing agents.

References

[1]	Friedmann T, Roblin R (1972) Gene therapy for human genetic disease? Science (New York, NY) 175: 949-955. doi: 10.1126/science.175.4025.949
[2]	Forsythe JA, Jiang BH, Iyer NV, et al. (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16: 4604-4613.
[3]	Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8: 129-138. doi: 10.1038/nrd2742
[4]	Caplen NJ, Alton E, Middleton PG, et al. (1995) Liposome-mediated CFTR gene-transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1: 39-46. doi: 10.1038/nm0195-39
[5]	Fujiwara T, Grimm EA, Mukhopadhyay T, et al. (1994) Induction of chemosensitivity in human lung cancer cells in-vivo by adenovirus-mediated transfer of the wild type P53 gene. Cancer Res 54: 2287-2291.
[6]	Merdan T, Kopecek J, Kissel T (2002) Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv Drug Delivery Rev 54: 715-758. doi: 10.1016/S0169-409X(02)00046-7
[7]	Abou-El-Enein M, Bauer G, Reinke P, et al. (2014) A roadmap toward clinical translation of genetically-modified stem cells for treatment of HIV. Trends Mol Med 20: 632-642. doi: 10.1016/j.molmed.2014.08.004
[8]	Carnio S, Novello S, Bironzo P, et al. (2014) Moving from histological subtyping to molecular characterization: new treatment opportunities in advanced non-small-cell lung cancer. Expert Review Anticancer Therapy 14: 1495-1513. doi: 10.1586/14737140.2014.949245
[9]	Pensado A, Seijo B, Sanchez A (2014) Current strategies for DNA therapy based on lipid nanocarriers. Expert Opinion Drug Delivery 11: 1721-1731. doi: 10.1517/17425247.2014.935337
[10]	Qasim W, Thrasher AJ (2014) Progress and prospects for engineered T cell therapies. Brit J Haematol 166: 818-829. doi: 10.1111/bjh.12981
[11]	Sahay G, Querbes W, Alabi C, et al. (2013) Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat Biotechnol 31: 653-U119. doi: 10.1038/nbt.2614
[12]	Schroeder A, Levins CG, Cortez C, et al. (2010) Lipid-based nanotherapeutics for siRNA delivery. J Intern Med 267: 9-21. doi: 10.1111/j.1365-2796.2009.02189.x
[13]	Xue W, Dahlman JE, Tammela T, et al. (2014) Small RNA combination therapy for lung cancer. P Natl Acad Sci U S A 111: E3553-E3561. doi: 10.1073/pnas.1412686111
[14]	Dahlman JE, Barnes C, Khan OF, et al. (2014) In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat Nanotechnol 9: 648-655. doi: 10.1038/nnano.2014.84
[15]	Ramamoorth M, Narvekar A (2015) Non viral vectors in gene therapy- an overview. J Clinical Diagnostic Res JCDR 9: GE01-06.
[16]	Yang J, Liu H, Zhang X (2014) Design, preparation and application of nucleic acid delivery carriers. Biotechnology Advances 32: 804-817. doi: 10.1016/j.biotechadv.2013.11.004
[17]	Choi YS, Lee MY, David AE, et al. (2014) Nanoparticles for gene delivery: therapeutic and toxic effects. Molecular Cellular Toxicology 10: 1-8. doi: 10.1007/s13273-014-0001-3
[18]	Dan N, Danino D (2014) Structure and kinetics of lipid-nucleic acid complexes. Adv Colloid Interface 205: 230-239. doi: 10.1016/j.cis.2014.01.013
[19]	Li S, Huang L (2000) Nonviral gene therapy: promises and challenges. Gene Ther 7: 31-34. doi: 10.1038/sj.gt.3301110
[20]	Mintzer MA, Simanek EE (2009) Nonviral vectors for gene delivery. Chem Rev 109: 259-302. doi: 10.1021/cr800409e
[21]	Schaffer DV, Fidelman NA, Dan N, et al. (2000) Vector unpacking as a potential barrier for receptor-mediated polyplex gene delivery. Biotechnol Bioeng 67: 598-606.
[22]	Radler JO, Koltover I, Salditt T, et al. (1997) Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science 275: 810-814. doi: 10.1126/science.275.5301.810
[23]	Koltover I, Salditt T, Radler JO, et al. (1998) An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281: 78-81.
[24]	Simberg D, Danino D, Talmon Y, et al. (2001) Phase behavior, DNA ordering, and size instability of cationic lipoplexes—Relevance to optimal transfection activity. J Biol Chem 276: 47453-47459. doi: 10.1074/jbc.M105588200
[25]	Evans HM, Ahmad A, Ewert K, et al. (2003) Structural polymorphism of DNA-dendrimer complexes. Phys Rev Lett 91: 075501. doi: 10.1103/PhysRevLett.91.075501
[26]	Merkel OM, Mintzer MA, Sitterberg J, et al. (2009) Triazine dendrimers as nonviral gene delivery systems: effects of molecular structure on biological activity. Bioconjug Chem 20: 1799-1806. doi: 10.1021/bc900243r
[27]	Juliano R, Alam MR, Dixit V, et al. (2008) Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides. Nucleic Acids Res 36: 4158-4171. doi: 10.1093/nar/gkn342
[28]	de Fougerolles A, Vornlocher HP, Maraganore J, et al. (2007) Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 6: 443-453. doi: 10.1038/nrd2310
[29]	Akinc A, Goldberg M, Qin J, et al. (2009) Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol Ther 17: 872-879. doi: 10.1038/mt.2009.36
[30]	Desigaux L, Sainlos M, Lambert O, et al. (2007) Self-assembled lamellar complexes of siRNA with lipidic aminoglycoside derivatives promote efficient siRNA delivery and interference. Proc Natl Acad Sci U S A 104: 16534-16539. doi: 10.1073/pnas.0707431104
[31]	Tros de Ilarduya C, Sun Y, Duzgunes N (2010) Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci 40: 159-170. doi: 10.1016/j.ejps.2010.03.019
[32]	Ma BC, Zhang SB, Jiang HM, et al. (2007) Lipoplex morphologies and their influences on transfection efficiency in gene delivery. J Controlled Release 123: 184-194. doi: 10.1016/j.jconrel.2007.08.022
[33]	Kapoor M, Burgess DJ, Patil SD (2012) Physicochemical characterization techniques for lipid based delivery systems for siRNA. Int J Pharm 427: 35-57. doi: 10.1016/j.ijpharm.2011.09.032
[34]	Wasungu L, Hoekstra D (2006) Cationic lipids, lipoplexes and intracellular delivery of genes. J Control Release 116: 255-264. doi: 10.1016/j.jconrel.2006.06.024
[35]	Safinya CR, Ewert KK, Leal C (2011) Cationic liposome-nucleic acid complexes: liquid crystal phases with applications in gene therapy. Liq Cryst 38: 1715-1723. doi: 10.1080/02678292.2011.624364
[36]	May S, Ben-Shaul A (1997) DNA-lipid complexes: stability of honeycomb-like and spaghetti-like structures. Biophys J 73: 2427-2440. doi: 10.1016/S0006-3495(97)78271-7
[37]	Harries D, May S, Gelbart WM, et al. (1998) Structure, stability, and thermodynamics of lamellar DNA-lipid complexes. Biophys J 75: 159-173. doi: 10.1016/S0006-3495(98)77503-4
[38]	Bruinsma R (1998) Electrostatics of DNA cationic lipid complexes: isoelectric instability. Eur Phys J B 4: 75-88.
[39]	Dan N (1996) Formation of ordered domains in membrane-bound DNA. Biophys J 71: 1267-1272. doi: 10.1016/S0006-3495(96)79326-8
[40]	Dan NL (1997) Multilamellar structures of DNA complexes with cationic liposomes. Biophys J 73: 1842-1846. doi: 10.1016/S0006-3495(97)78214-6
[41]	Dan N (1998) The structure of DNA complexes with cationic liposomes—cylindrical or flat bilayers? BBA-Biomembranes 1369: 34-38. doi: 10.1016/S0005-2736(97)00171-5
[42]	Simberg D, Danino D, Talmon Y, et al. (2001) Phase behavior, DNA ordering, and size instability of cationic lipoplexes—Relevance to optimal transfection activity. J Biol Chem 276: 47453-47459. doi: 10.1074/jbc.M105588200
[43]	Simberg D, Danino D, Talmon Y, et al. (2003) Phase behavior, DNA ordering and size instability of cationic lipoplexes: Relevance to optimal transfection activity. J Liposome Res 13: 86-87.
[44]	Kastner E, Kaur R, Lowry D, et al. (2014) High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. Int J Pharm 477: 361-368. doi: 10.1016/j.ijpharm.2014.10.030
[45]	Balbino TA, Azzoni AR, de la Torre LG (2013) Microfluidic devices for continuous production of pDNA/cationic liposome complexes for gene delivery and vaccine therapy. Colloid Surface B 111: 203-210. doi: 10.1016/j.colsurfb.2013.04.003
[46]	Chen D, Love KT, Chen Y, et al. (2012) Rapid Discovery of Potent siRNA-Containing Lipid Nanoparticles Enabled by Controlled Microfluidic Formulation. J Am Chem Soc 134: 6948-6951. doi: 10.1021/ja301621z
[47]	Kennedy MT, Pozharski EV, Rakhmanova VA, et al. (2000) Factors governing the assembly of cationic phospholipid-DNA complexes. Biophys J 78: 1620-1633. doi: 10.1016/S0006-3495(00)76714-2
[48]	Pozharski EV, MacDonald RC (2007) Single lipoplex study of cationic lipoid-DNA, self-assembled complexes. Mol Pharm 4: 962-974. doi: 10.1021/mp700080m
[49]	Barreleiro PCA, Lindman B (2003) The kinetics of DNA-cationic vesicle complex formation. JPhys Chem B 107: 6208-6213. doi: 10.1021/jp0277107
[50]	Junquera E, Aicart E (2014) Cationic Lipids as Transfecting Agents of DNA in Gene Therapy. Current Topics Medicinal Chem 14: 649-663. doi: 10.2174/1568026614666140118203128
[51]	Ma B, Zhang S, Jiang H, et al. (2007) Lipoplex morphologies and their influences on transfection efficiency in gene delivery. J Control Release 123: 184-194. doi: 10.1016/j.jconrel.2007.08.022
[52]	Xiong F, Mi Z, Gu N (2011) Cationic liposomes as gene delivery system: transfection efficiency and new application. Pharmazie 66: 158-164.
[53]	Zhdanov RI, Podobed OV, Vlassov VV (2002) Cationic lipid-DNA complexes-lipoplexes-for gene transfer and therapy. Bioelectrochemistry 58: 53-64. doi: 10.1016/S1567-5394(02)00132-9
[54]	Cullis PR, de Kruijff B (1979) Lipid polymorphism and the functional roles of lipids in biological membranes. Biochim Biophys Acta 559: 399-420. doi: 10.1016/0304-4157(79)90012-1
[55]	Epand RM (1998) Lipid polymorphism and protein-lipid interactions. Biochim Biophys Acta 1376: 353-368. doi: 10.1016/S0304-4157(98)00015-X
[56]	Seddon JM (1990) STRUCTURE OF THE INVERTED HEXAGONAL (HII) PHASE, AND NON-LAMELLAR PHASE-TRANSITIONS OF LIPIDS. Biochim Biophys Acta 1031: 1-69. doi: 10.1016/0304-4157(90)90002-T
[57]	Netz RR, Andelman D (2003) Neutral and charged polymers at interfaces. Phys Rep 380: 1-95. doi: 10.1016/S0370-1573(03)00118-2
[58]	Nelson P (2013) Biological Physics: Freeman.
[59]	Gregory J, Barany S (2011) Adsorption and flocculation by polymers and polymer mixtures. Adv Colloid Interface 169: 1-12. doi: 10.1016/j.cis.2011.06.004
[60]	G. Fleer, M.A. Cohen Stuart, J.M.H.M. Scheutjens, et al. (1993) Polymers at Interfaces Springer;.
[61]	Sukhishvili SA, Granick S (1998) Polyelectrolyte adsorption onto an initially-bare solid surface of opposite electrical charge. J Chem Phys 109: 6861-6868. doi: 10.1063/1.477253
[62]	Pozharski E, MacDonald RC (2002) Thermodynamics of cationic lipid-DNA complex formation as studied by isothermal titration calorimetry. Biophys J 83: 556-565. doi: 10.1016/S0006-3495(02)75191-6
[63]	Pozharski E, MacDonald RC (2003) Lipoplex thermodynamics: Determination of DNA-cationic lipoid interaction energies. Biophys J 85: 3969-3978. doi: 10.1016/S0006-3495(03)74811-5
[64]	Koltover I, Salditt T, Safinya CR (1999) Phase diagram, stability, and overcharging of lamellar cationic lipid-DNA self-assembled complexes. Biophys J 77: 915-924. doi: 10.1016/S0006-3495(99)76942-0
[65]	Ahsan A, Rudnick J, Bruinsma R (1998) Elasticity theory of the B-DNA to S-DNA transition. Biophys J 74: 132-137. doi: 10.1016/S0006-3495(98)77774-4
[66]	Hirsch-Lerner D, Barenholz Y (1999) Hydration of lipoplexes commonly used in gene delivery: follow-up by laurdan fluorescence changes and quantification by differential scanning calorimetry. Biochimica Et Biophysica Acta-Biomembranes 1461: 47-57. doi: 10.1016/S0005-2736(99)00145-5
[67]	Tilcock CP, Bally MB, Farren SB, et al. (1982) Influence of cholesterol on the structural preferences of dioleoylphosphatidylethanolamine-dioleoylphosphatidylcholine systems: a phosphorus-31 and deuterium nuclear magnetic resonance study. Biochemistry 21: 4596-4601. doi: 10.1021/bi00262a013
[68]	Danino D, Kesselman E, Saper G, et al. (2009) Osmotically induced reversible transitions in lipid-DNA mesophases. Biophys J 96: L43-45. doi: 10.1016/j.bpj.2008.12.3887
[69]	Scarzello M, Chupin V, Wagenaar A, et al. (2005) Polymorphism of pyridinium amphiphiles for gene delivery: influence of ionic strength, helper lipid content, and plasmid DNA complexation. Biophys J 88: 2104-2113. doi: 10.1529/biophysj.104.053983
[70]	Ewert KK, Evans HM, Zidovska A, et al. (2006) A columnar phase of dendritic lipid-based cationic liposome-DNA complexes for gene delivery: hexagonally ordered cylindrical micelles embedded in a DNA honeycomb lattice. J Am Chem Soc 128: 3998-4006. doi: 10.1021/ja055907h
[71]	Zidovska A, Evans HM, Ewert KK, et al. (2009) Liquid crystalline phases of dendritic lipid-DNA self-assemblies: lamellar, hexagonal, and DNA bundles. J Phys Chem B 113: 3694-3703. doi: 10.1021/jp806863z
[72]	Wasungu L, Stuart MC, Scarzello M, et al. (2006) Lipoplexes formed from sugar-based gemini surfactants undergo a lamellar-to-micellar phase transition at acidic pH. Evidence for a non-inverted membrane-destabilizing hexagonal phase of lipoplexes. Biochim Biophys Acta 1758: 1677-1684.
[73]	Bilalov A, Olsson U, Lindman B (2009) A cubic DNA-lipid complex. Soft Matter 5: 3827-3830. doi: 10.1039/b908939j
[74]	Larsson K (1983) Two cubic phases in monoolein-water system. Nature.
[75]	Leal C, Ewert KK, Bouxsein NF, et al. (2013) Stacking of Short DNA Induces the Gyroid Cubic-to-Inverted Hexagonal Phase Transition in Lipid-DNA Complexes. Soft Matter 9: 795-804. doi: 10.1039/C2SM27018H
[76]	Farago O, Ewert K, Ahmad A, et al. (2008) Transitions between distinct compaction regimes in complexes of multivalent cationic lipids and DNA. Biophys J 95: 836-846. doi: 10.1529/biophysj.107.124669
[77]	Fire A, Xu S, Montgomery MK, et al. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391: 806-811. doi: 10.1038/35888
[78]	Davidson BL, Paulson HL (2004) Molecular medicine for the brain: silencing of disease genes with RNA interference. Lancet Neurol 3: 145-149. doi: 10.1016/S1474-4422(04)00678-7
[79]	Ponnappa BC (2009) siRNA for inflammatory diseases. Curr Opin Investig Drugs 10: 418-424.
[80]	Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8: 129-138. doi: 10.1038/nrd2742
[81]	Takeshita F, Ochiya T (2006) Therapeutic potential of RNA interference against cancer. Cancer Sci 97: 689-696. doi: 10.1111/j.1349-7006.2006.00234.x
[82]	Leal C, Bouxsein NF, Ewert KK, et al. (2010) Highly efficient gene silencing activity of siRNA embedded in a nanostructured gyroid cubic lipid matrix. J Am Chem Soc 132: 16841-16847. doi: 10.1021/ja1059763
[83]	Leal C, Ewert KK, Shirazi RS, et al. (2011) Nanogyroids incorporating multivalent lipids: enhanced membrane charge density and pore forming ability for gene silencing. Langmuir 27: 7691-7697. doi: 10.1021/la200679x
[84]	Aytar BS, Muller JP, Kondo Y, et al. (2013) Redox-based control of the transformation and activation of siRNA complexes in extracellular environments using ferrocenyl lipids. J Am Chem Soc 135: 9111-9120. doi: 10.1021/ja403546b
[85]	Schroeder A, Levins CG, Cortez C, et al. (2010) Lipid-based nanotherapeutics for siRNA delivery. J Intern Med 267: 9-21. doi: 10.1111/j.1365-2796.2009.02189.x
[86]	Kim DH, Rossi JJ (2007) Strategies for silencing human disease using RNA interference. Nat Revs Genet 8: 173-184. doi: 10.1038/nrg2006
[87]	De Paula D, Bentley MV, Mahato RI (2007) Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting. RNA 13: 431-456. doi: 10.1261/rna.459807
[88]	A.S. Edelstein, Cammarata RC (1996) Nanomaterials: Synthesis, Properties and Applications: Inst. of Physics Publishing.
[89]	Filippova NL (1998) Adsorption and desorption kinetics of polyelectrolytes on planar surfaces. Langmuir 14: 1162-1176. doi: 10.1021/la970544n
[90]	Iruthayaraj J, Poptoshev E, Vareikis AV, et al. (2005) Adsorption of low charge density polyelectrolyte containing poly(ethylene oxide) side chains on silica: Effects of ionic strength and pH. Macromolecules 38: 6152-6160. doi: 10.1021/ma050851x
[91]	Sedeva IG, Fornasiero D, Ralston J, et al. (2009) The Influence of Surface Hydrophobicity on Polyacrylamide Adsorption. Langmuir 25: 4514-4521. doi: 10.1021/la803838k
[92]	McFarlane A, Yeap KY, Bremmell K, et al. (2008) The influence of flocculant adsorption kinetics on the dewaterability of kaolinite and smectite clay mineral dispersions. Colloid Surface A 317: 39-48. doi: 10.1016/j.colsurfa.2007.09.045
[93]	Enarsson L-E, Wagberg L (2008) Adsorption kinetics of cationic polyelectrolytes studied with stagnation point adsorption reflectometry and quartz crystal microgravimetry. Langmuir 24: 7329-7337. doi: 10.1021/la800198e
[94]	van Heiningen JA, Hill RJ (2011) Polymer adsorption onto a micro-sphere from optical tweezers electrophoresis. Lab Chip 11: 152-162. doi: 10.1039/C005217P
[95]	Dickinson E, Eriksson L (1991) Particle flocculation by adsorbing polymers. Adv Colloid Interfac 34: 1-29. doi: 10.1016/0001-8686(91)80045-L
[96]	Barany S, Szepesszentgyorgyi A (2004) Flocculation of cellular suspensions by polyelectrolytes. Adv Colloid Interfac 111: 117-129. doi: 10.1016/j.cis.2004.07.003
[97]	Popa I, Gillies G, Papastavrou G, et al. (2009) Attractive Electrostatic Forces between Identical Colloidal Particles Induced by Adsorbed Polyelectrolytes. J Phys Chem B 113: 8458-8461. doi: 10.1021/jp904041k
[98]	Popa I, Gillies G, Papastavrou G, et al. (2010) Attractive and Repulsive Electrostatic Forces between Positively Charged Latex Particles in the Presence of Anionic Linear Polyelectrolytes. J Phys Chem B 114: 3170-3177. doi: 10.1021/jp911482a
[99]	Lin MY, Lindsay HM, Weitz DA, et al. (1989) Universality in colloid aggregation. Nature 339: 360-362. doi: 10.1038/339360a0
[100]	S. Edelstein, Cammarata RC (1996) Nanomaterials: Synthesis, Properties and Applications: Inst. of Physics Publishing, London, UK.
[101]	Lai E, van Zanten JH (2002) Real time monitoring of lipoplex molar mass, size and density. J Control Release 82: 149-158. doi: 10.1016/S0168-3659(02)00104-9
[102]	Lai E, van Zanten JH (2001) Monitoring DNA/poly-L-lysine polyplex formation with time-resolved multiangle laser light scattering. Biophys J 80: 864-873. doi: 10.1016/S0006-3495(01)76065-1
[103]	Gershon H, Ghirlando R, Guttman SB, et al. (1993) Mode of formation and structural features of DNA-cationic liposome complexes used for transfection. Biochemistry 32: 7143-7151. doi: 10.1021/bi00079a011
[104]	Zhang Y, Garzon-Rodriguez W, Manning MC, et al. (2003) The use of fluorescence resonance energy transfer to monitor dynamic changes of lipid-DNA interactions during lipoplex formation. Biochim Biophys Acta 1614: 182-192. doi: 10.1016/S0005-2736(03)00177-9
[105]	Braun CS, Fisher MT, Tomalia DA, et al. (2005) A stopped-flow kinetic study of the assembly of nonviral gene delivery complexes. Biophys J 88: 4146-4158. doi: 10.1529/biophysj.104.055202
[106]	Barreleiro PC, May RP, Lindman B (2003) Mechanism of formation of DNA-cationic vesicle complexes. Faraday Discuss 122: 191-201; discussion 269-182. doi: 10.1039/b200796g
[107]	Leal C, Sandstrom D, Nevsten P, et al. (2008) Local and translational dynamics in DNA-lipid assemblies monitored by solid-state and diffusion NMR. BBA-Biomembranes 1778: 214-228. doi: 10.1016/j.bbamem.2007.09.035
[108]	Zuidam NJ, Barenholz Y (1997) Electrostatic parameters of cationic liposomes commonly used for gene delivery as determined by 4-heptadecyl-7-hydroxycoumarin. Biochim Biophys Acta 1329: 211-222. doi: 10.1016/S0005-2736(97)00110-7
[109]	Zuidam NJ, Barenholz Y (1998) Electrostatic and structural properties of complexes involving plasmid DNA and cationic lipids commonly used for gene delivery. Biochim Biophys Acta 1368: 115-128. doi: 10.1016/S0005-2736(97)00187-9
[110]	Szilagyi I, Trefalt G, Tiraferri A, et al. (2014) Polyelectrolyte adsorption, interparticle forces, and colloidal aggregation. Soft Matter 10: 2479-2502. doi: 10.1039/c3sm52132j
[111]	Maier B, Radler JO (1999) Conformation and self-diffusion of single DNA molecules confined to two dimensions. Phys Rev Lett 82: 1911-1914. doi: 10.1103/PhysRevLett.82.1911
[112]	Epand RF, Sarig H, Ohana D, et al. (2011) Physical properties affecting cochleate formation and morphology using antimicrobial oligo-acyl-lysyl peptide mimetics and mixtures mimicking the composition of bacterial membranes in the absence of divalent cations. J Phys Chem B 115: 2287-2293. doi: 10.1021/jp111242q
[113]	Epand RF, Mor A, Epand RM (2011) Lipid complexes with cationic peptides and OAKs; their role in antimicrobial action and in the delivery of antimicrobial agents. Cell Mol Life Sci 68: 2177-2188. doi: 10.1007/s00018-011-0711-9
[114]	Sarig H, Ohana D, Epand RF, et al. (2011) Functional studies of cochleate assemblies of an oligo-acyl-lysyl with lipid mixtures for combating bacterial multidrug resistance. FASEB J 25: 3336-3343. doi: 10.1096/fj.11-183764
[115]	Chen DL, Love KT, Chen Y, et al. (2012) Rapid Discovery of Potent siRNA-Containing Lipid Nanoparticles Enabled by Controlled Microfluidic Formulation. J Am Chem Soc 134: 6948-6951. doi: 10.1021/ja301621z
[116]	Leung AKK, Hafez IM, Baoukina S, et al. (2012) Lipid Nanoparticles Containing siRNA Synthesized by Microfluidic Mixing Exhibit an Electron-Dense Nanostructured Core (vol 116, pg 18440, 2012). J Phys Chem C 116: 22104-22104. doi: 10.1021/jp3088786

Reader Comments

Your name:*

Email:*
© 2015 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)