Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes

Che Fu Liu; Raymond Chen; Joseph A. Frezzo; Priya Katyal; Lindsay K. Hill; Liming Yin; Nikita Srivastava; Haresh T. More; P. Douglas Renfrew; Richard Bonneau; Jin Kim Montclare

doi:10.1021/acs.biomac.7b00203

Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes

Che Fu Liu, Raymond Chen, Joseph A. Frezzo, Priya Katyal, Lindsay K. Hill, Liming Yin, Nikita Srivastava, Haresh T. More, P. Douglas Renfrew, Richard Bonneau, Jin Kim Montclare

Research output: Contribution to journal › Article › peer-review

Abstract

An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.

Original language	English (US)
Pages (from-to)	2688-2698
Number of pages	11
Journal	Biomacromolecules
Volume	18
Issue number	9
DOIs	https://doi.org/10.1021/acs.biomac.7b00203
State	Published - Sep 11 2017

ASJC Scopus subject areas

Bioengineering
Biomaterials
Polymers and Plastics
Materials Chemistry

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10.1021/acs.biomac.7b00203

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@article{c2a847db81a14548905f60e7c357232d,

title = "Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes",

abstract = "An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.",

author = "Liu, {Che Fu} and Raymond Chen and Frezzo, {Joseph A.} and Priya Katyal and Hill, {Lindsay K.} and Liming Yin and Nikita Srivastava and More, {Haresh T.} and Renfrew, {P. Douglas} and Richard Bonneau and Montclare, {Jin Kim}",

note = "Funding Information: This work was supported by NSF DMR-1505214 (J.K.M.) and in part by the NSF MRSEC Program under Award Number DMR-1420073 and NYU CTSI grant from the National Center for Advancing Translational Sciences (NCATS), NIH (UL1TR000038). P.D.R. and R.B. are funded by the Flatiron Institute. We thank the Flatiron Scientific Computing Core for computational support. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

year = "2017",

month = sep,

day = "11",

doi = "10.1021/acs.biomac.7b00203",

language = "English (US)",

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T1 - Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes

AU - Liu, Che Fu

AU - Chen, Raymond

AU - Frezzo, Joseph A.

AU - Katyal, Priya

AU - Hill, Lindsay K.

AU - Yin, Liming

AU - Srivastava, Nikita

AU - More, Haresh T.

AU - Renfrew, P. Douglas

AU - Bonneau, Richard

AU - Montclare, Jin Kim

N1 - Funding Information: This work was supported by NSF DMR-1505214 (J.K.M.) and in part by the NSF MRSEC Program under Award Number DMR-1420073 and NYU CTSI grant from the National Center for Advancing Translational Sciences (NCATS), NIH (UL1TR000038). P.D.R. and R.B. are funded by the Flatiron Institute. We thank the Flatiron Scientific Computing Core for computational support. Publisher Copyright: © 2017 American Chemical Society.

PY - 2017/9/11

Y1 - 2017/9/11

N2 - An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.

AB - An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.

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Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes

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