Mechanistic differences in DNA nanoparticle formation in the presence of oligolysines and poly-L-lysine

被引:43
作者
Nayvelt, Irina
Thomas, Thresia
Thomas, T. J.
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA
[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Environm & Occupat Med, New Brunswick, NJ 08903 USA
[3] Canc Inst New Jersey, New Brunswick, NJ 08903 USA
[4] Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA
[5] Rutgers State Univ, Grad Program Nutr Sci, New Brunswick, NJ 08903 USA
关键词
D O I
10.1021/bm0605863
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We studied the effectiveness of trilysine (Lys(3)), tetralysine (Lys(4)), pentalysine (Lys(5)), and poly-L-lysine (PLL) (MW 50000) on lambda-DNA nanoparticle formation and characterized the size, shape, and stability of nanoparticles. Light scattering experiments showed EC50 (lysine concentration at 50% DNA compaction) values of similar to 0.0036, 2, and 20 mu mol/L, respectively, for PLL, Lys(5), and Lys(4) at 10 mM [Na+]. Plots of log EC50 versus log [Na+] showed positive slopes of 1.09 and 1.7, respectively, for Lys(4) and Lys(5) and a negative slope of -0.1 for PLL. Hydrodynamic radii of oligolysine condensed particles increased (48-173 nm) with increasing [Na+], whereas no significant change occurred to nanoparticles formed with PLL. There was an increase in the size of nanoparticles formed with Lys(5) at > 40 degrees C, whereas no such change occurred with PLL. The DNA melting temperature increased with oligolysine concentration. These results indicate distinct differences in the mechanism(s) by which oligolysines and PLL provoke DNA condensation to nanoparticles.
引用
收藏
页码:477 / 484
页数:8
相关论文
共 53 条
[21]   Poly-L-lysine improves gene transfer with adenovirus formulated in PLGA microspheres [J].
Matthews, CB ;
Jenkins, G ;
Hilfinger, JM ;
Davidson, BL .
GENE THERAPY, 1999, 6 (09) :1558-1564
[22]   Thermodynamics of cationic lipid binding to DNA and DNA condensation: Roles of electrostatics and hydrophobicity [J].
Matulis, D ;
Rouzina, I ;
Bloomfield, VA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (25) :7331-7342
[23]   Single-stranded DNA condensed with poly-L-lysine results in nanometric particles that are significantly smaller, more stable in physiological ionic strength fluids and afford higher efficiency of gene delivery than their double-stranded counterparts [J].
Molas, M ;
Bartrons, R ;
Perales, JC .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2002, 1572 (01) :37-44
[24]   ON STRUCTURE AND STABILITY OF DNA-PROTAMINE AND DNA-POLYPEPTIDE COMPLEXES [J].
OLINS, DE ;
OLINS, AL ;
VONHIPPE.PH .
JOURNAL OF MOLECULAR BIOLOGY, 1968, 33 (01) :265-&
[25]   Controlled release systems for DNA delivery [J].
Pannier, AK ;
Shea, LD .
MOLECULAR THERAPY, 2004, 10 (01) :19-26
[26]   Compositional regulation of poly(lysine-g-(lactide-b-ethylene glycol))-DNA complexation and stability [J].
Park, S ;
Healy, KE .
JOURNAL OF CONTROLLED RELEASE, 2004, 95 (03) :639-651
[27]   Biochemical and functional characterization of DNA complexes capable of targeting genes to hepatocytes via the asialoglycoprotein receptor [J].
Perales, JC ;
Grossmann, GA ;
Molas, M ;
Liu, G ;
Ferkol, T ;
Harpst, J ;
Oda, H ;
Hanson, RW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (11) :7398-7407
[28]   Star-shaped poly(ethylene glycol)-block-polyethylenimine copolymers enhance DNA condensation of low molecular weight polyethylenimines [J].
Petersen, H ;
Kunath, K ;
Martin, AL ;
Stolnik, S ;
Roberts, CJ ;
Davies, MC ;
Kissel, T .
BIOMACROMOLECULES, 2002, 3 (05) :926-936
[29]   Branched cationic peptides for gene delivery:: Role of type and number of cationic residues in formation and in vitro activity of DNA polyplexes [J].
Plank, C ;
Tang, MX ;
Wolfe, AR ;
Szoka, FC .
HUMAN GENE THERAPY, 1999, 10 (02) :319-332
[30]   THERMODYNAMIC ANALYSIS OF ION EFFECTS ON BINDING AND CONFORMATIONAL EQUILIBRIA OF PROTEINS AND NUCLEIC-ACIDS - ROLES OF ION ASSOCIATION OR RELEASE, SCREENING, AND ION EFFECTS ON WATER ACTIVITY [J].
RECORD, MT ;
ANDERSON, CF ;
LOHMAN, TM .
QUARTERLY REVIEWS OF BIOPHYSICS, 1978, 11 (02) :103-178