Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging.

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Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging. / Majzoub, Ramsey N; Chan, Chia-Ling; Ewert, Kai K; Silva, Bruno; Liang, Keng S; Jacovetty, Erica L; Carragher, Bridget; Potter, Clinton S; Safinya, Cyrus R.

In: Biomaterials, Vol. 35, No. 18, 2014, p. 4996-5005.

Research output: Contribution to journalArticle

Harvard

Majzoub, RN, Chan, C-L, Ewert, KK, Silva, B, Liang, KS, Jacovetty, EL, Carragher, B, Potter, CS & Safinya, CR 2014, 'Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging.', Biomaterials, vol. 35, no. 18, pp. 4996-5005. https://doi.org/10.1016/j.biomaterials.2014.03.007

APA

Majzoub, R. N., Chan, C-L., Ewert, K. K., Silva, B., Liang, K. S., Jacovetty, E. L., ... Safinya, C. R. (2014). Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging. Biomaterials, 35(18), 4996-5005. https://doi.org/10.1016/j.biomaterials.2014.03.007

CBE

Majzoub RN, Chan C-L, Ewert KK, Silva B, Liang KS, Jacovetty EL, Carragher B, Potter CS, Safinya CR. 2014. Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging. Biomaterials. 35(18):4996-5005. https://doi.org/10.1016/j.biomaterials.2014.03.007

MLA

Vancouver

Author

Majzoub, Ramsey N ; Chan, Chia-Ling ; Ewert, Kai K ; Silva, Bruno ; Liang, Keng S ; Jacovetty, Erica L ; Carragher, Bridget ; Potter, Clinton S ; Safinya, Cyrus R. / Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging. In: Biomaterials. 2014 ; Vol. 35, No. 18. pp. 4996-5005.

RIS

TY - JOUR

T1 - Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging.

AU - Majzoub, Ramsey N

AU - Chan, Chia-Ling

AU - Ewert, Kai K

AU - Silva, Bruno

AU - Liang, Keng S

AU - Jacovetty, Erica L

AU - Carragher, Bridget

AU - Potter, Clinton S

AU - Safinya, Cyrus R

PY - 2014

Y1 - 2014

N2 - Steric stabilization of cationic liposome-DNA (CL-DNA) complexes is required for in vivo applications such as gene therapy. PEGylation (PEG: poly(ethylene glycol)) of CL-DNA complexes by addition of PEG2000-lipids yields sterically stabilized nanoparticles but strongly reduces their gene delivery efficacy. PEGylation-induced weakening of the electrostatic binding of CL-DNA nanoparticles to cells (leading to reduced uptake) has been considered as a possible cause, but experimental results have been ambiguous. Using quantitative live-cell imaging in vitro, we have investigated cell attachment and uptake of PEGylated CL-DNA nanoparticles with and without a custom synthesized RGD-peptide grafted to the distal ends of PEG2000-lipids. The RGD-tagged nanoparticles exhibit strongly increased cellular attachment as well as uptake compared to nanoparticles without grafted peptide. Transfection efficiency of RGD-tagged PEGylated CL-DNA NPs increases by about an order of magnitude between NPs with low and high membrane charge density (σM; the average charge per unit area of the membrane; controlled by the molar ratio of cationic to neutral lipid), even though imaging data show that uptake of RGD-tagged particles is only slightly enhanced by high σM. This suggests that endosomal escape and, as a result, transfection efficiency of RGD-tagged NPs is facilitated by high σM. We present a model describing the interactions between PEGylated CL-DNA nanoparticles and the anionic cell membrane which shows how the PEG grafting density and membrane charge density affect adhesion of nanoparticles to the cell surface.

AB - Steric stabilization of cationic liposome-DNA (CL-DNA) complexes is required for in vivo applications such as gene therapy. PEGylation (PEG: poly(ethylene glycol)) of CL-DNA complexes by addition of PEG2000-lipids yields sterically stabilized nanoparticles but strongly reduces their gene delivery efficacy. PEGylation-induced weakening of the electrostatic binding of CL-DNA nanoparticles to cells (leading to reduced uptake) has been considered as a possible cause, but experimental results have been ambiguous. Using quantitative live-cell imaging in vitro, we have investigated cell attachment and uptake of PEGylated CL-DNA nanoparticles with and without a custom synthesized RGD-peptide grafted to the distal ends of PEG2000-lipids. The RGD-tagged nanoparticles exhibit strongly increased cellular attachment as well as uptake compared to nanoparticles without grafted peptide. Transfection efficiency of RGD-tagged PEGylated CL-DNA NPs increases by about an order of magnitude between NPs with low and high membrane charge density (σM; the average charge per unit area of the membrane; controlled by the molar ratio of cationic to neutral lipid), even though imaging data show that uptake of RGD-tagged particles is only slightly enhanced by high σM. This suggests that endosomal escape and, as a result, transfection efficiency of RGD-tagged NPs is facilitated by high σM. We present a model describing the interactions between PEGylated CL-DNA nanoparticles and the anionic cell membrane which shows how the PEG grafting density and membrane charge density affect adhesion of nanoparticles to the cell surface.

U2 - 10.1016/j.biomaterials.2014.03.007

DO - 10.1016/j.biomaterials.2014.03.007

M3 - Article

VL - 35

SP - 4996

EP - 5005

JO - Biomaterials

T2 - Biomaterials

JF - Biomaterials

SN - 1878-5905

IS - 18

ER -