Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA

Rae Sung Chang; Min Sung Suh; Sunil Kim; Gayong Shim; Sangbin Lee; Sung Sik Han; Kyung Eun Lee; Hyesung Jeon; Han Gon Choi; Yongseok Choi; Chan Wha Kim; Yu Kyoung Oh

doi:10.1016/j.biomaterials.2011.09.017

Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA

Rae Sung Chang, Min Sung Suh, Sunil Kim, Gayong Shim, Sangbin Lee, Sung Sik Han, Kyung Eun Lee, Hyesung Jeon, Han Gon Choi, Yongseok Choi, Chan Wha Kim, Yu Kyoung Oh

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

65 Citations (Scopus)

Abstract

Combined treatment of anticancer drugs and small interfering RNAs (siRNAs) have emerged as a new modality of anticancer therapy. Here, we describe a co-delivery system of anticancer drugs and siRNA in which anticancer drug-derived lipids form cationic nanoparticles for siRNA complexation. The anticancer drug mitoxantrone (MTO) was conjugated to palmitoleic acid, generating two types of palmitoleyl MTO (Pal-MTO) lipids: monopalmitoleyl MTO (mono-Pal-MTO) and dipalmitoleyl MTO (di-Pal-MTO). Among various lipid compositions of MTO, nanoparticles containing mono-Pal-MTO and di-Pal-MTO at a molar ratio of 1:1 (md11-Pal-MTO nanoparticles) showed the most efficient cellular delivery of siRNA, higher than that of Lipofectamine 2000. Delivery of red fluorescence protein-specific siRNA into B16F10-RFP cells using md11-Pal-MTO nanoparticles reduced the expression of RFP at both mRNA and protein levels, demonstrating silencing of the siRNA target gene. Moreover, delivery of Mcl-1-specific anticancer siRNA (siMcl-1) using md11-Pal-MTO enhanced antitumor activity in vitro, reducing tumor cell viability by 81% compared to a reduction of 68% following Lipofectamine 2000-mediated transfection of siMcl-1. Intratumoral administration of siMcl-1 using md11-Pal-MTO nanoparticles significantly inhibited tumor growth, reducing tumor size by 83% compared to untreated controls. Our results suggest the potential of md11-Pal-MTO multifunctional nanoparticles for co-delivery of anticancer siRNAs for effective combination therapy.

Original language	English
Pages (from-to)	9785-9795
Number of pages	11
Journal	Biomaterials
Volume	32
Issue number	36
DOIs	https://doi.org/10.1016/j.biomaterials.2011.09.017
Publication status	Published - 2011 Dec

Keywords

Anticancer chemo-gene therapy
Co-delivery
Mitoxantrone
Multifunctional nanoparticles
SiRNA

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2011.09.017

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@article{65fbeff660de4ba68a54c473e50778ad,

title = "Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA",

abstract = "Combined treatment of anticancer drugs and small interfering RNAs (siRNAs) have emerged as a new modality of anticancer therapy. Here, we describe a co-delivery system of anticancer drugs and siRNA in which anticancer drug-derived lipids form cationic nanoparticles for siRNA complexation. The anticancer drug mitoxantrone (MTO) was conjugated to palmitoleic acid, generating two types of palmitoleyl MTO (Pal-MTO) lipids: monopalmitoleyl MTO (mono-Pal-MTO) and dipalmitoleyl MTO (di-Pal-MTO). Among various lipid compositions of MTO, nanoparticles containing mono-Pal-MTO and di-Pal-MTO at a molar ratio of 1:1 (md11-Pal-MTO nanoparticles) showed the most efficient cellular delivery of siRNA, higher than that of Lipofectamine 2000. Delivery of red fluorescence protein-specific siRNA into B16F10-RFP cells using md11-Pal-MTO nanoparticles reduced the expression of RFP at both mRNA and protein levels, demonstrating silencing of the siRNA target gene. Moreover, delivery of Mcl-1-specific anticancer siRNA (siMcl-1) using md11-Pal-MTO enhanced antitumor activity in vitro, reducing tumor cell viability by 81% compared to a reduction of 68% following Lipofectamine 2000-mediated transfection of siMcl-1. Intratumoral administration of siMcl-1 using md11-Pal-MTO nanoparticles significantly inhibited tumor growth, reducing tumor size by 83% compared to untreated controls. Our results suggest the potential of md11-Pal-MTO multifunctional nanoparticles for co-delivery of anticancer siRNAs for effective combination therapy.",

keywords = "Anticancer chemo-gene therapy, Co-delivery, Mitoxantrone, Multifunctional nanoparticles, SiRNA",

author = "Chang, {Rae Sung} and Suh, {Min Sung} and Sunil Kim and Gayong Shim and Sangbin Lee and Han, {Sung Sik} and Lee, {Kyung Eun} and Hyesung Jeon and Choi, {Han Gon} and Yongseok Choi and Kim, {Chan Wha} and Oh, {Yu Kyoung}",

note = "Funding Information: This work was supported by research grants from Ministry of Education, Science and Technology ( 2010K-001245; 2011K-000809 ), and from the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government (No. 20110019640 ). ",

year = "2011",

month = dec,

doi = "10.1016/j.biomaterials.2011.09.017",

language = "English",

volume = "32",

pages = "9785--9795",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "36",

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T1 - Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA

AU - Chang, Rae Sung

AU - Suh, Min Sung

AU - Kim, Sunil

AU - Shim, Gayong

AU - Lee, Sangbin

AU - Han, Sung Sik

AU - Lee, Kyung Eun

AU - Jeon, Hyesung

AU - Choi, Han Gon

AU - Choi, Yongseok

AU - Kim, Chan Wha

AU - Oh, Yu Kyoung

N1 - Funding Information: This work was supported by research grants from Ministry of Education, Science and Technology ( 2010K-001245; 2011K-000809 ), and from the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government (No. 20110019640 ).

PY - 2011/12

Y1 - 2011/12

N2 - Combined treatment of anticancer drugs and small interfering RNAs (siRNAs) have emerged as a new modality of anticancer therapy. Here, we describe a co-delivery system of anticancer drugs and siRNA in which anticancer drug-derived lipids form cationic nanoparticles for siRNA complexation. The anticancer drug mitoxantrone (MTO) was conjugated to palmitoleic acid, generating two types of palmitoleyl MTO (Pal-MTO) lipids: monopalmitoleyl MTO (mono-Pal-MTO) and dipalmitoleyl MTO (di-Pal-MTO). Among various lipid compositions of MTO, nanoparticles containing mono-Pal-MTO and di-Pal-MTO at a molar ratio of 1:1 (md11-Pal-MTO nanoparticles) showed the most efficient cellular delivery of siRNA, higher than that of Lipofectamine 2000. Delivery of red fluorescence protein-specific siRNA into B16F10-RFP cells using md11-Pal-MTO nanoparticles reduced the expression of RFP at both mRNA and protein levels, demonstrating silencing of the siRNA target gene. Moreover, delivery of Mcl-1-specific anticancer siRNA (siMcl-1) using md11-Pal-MTO enhanced antitumor activity in vitro, reducing tumor cell viability by 81% compared to a reduction of 68% following Lipofectamine 2000-mediated transfection of siMcl-1. Intratumoral administration of siMcl-1 using md11-Pal-MTO nanoparticles significantly inhibited tumor growth, reducing tumor size by 83% compared to untreated controls. Our results suggest the potential of md11-Pal-MTO multifunctional nanoparticles for co-delivery of anticancer siRNAs for effective combination therapy.

AB - Combined treatment of anticancer drugs and small interfering RNAs (siRNAs) have emerged as a new modality of anticancer therapy. Here, we describe a co-delivery system of anticancer drugs and siRNA in which anticancer drug-derived lipids form cationic nanoparticles for siRNA complexation. The anticancer drug mitoxantrone (MTO) was conjugated to palmitoleic acid, generating two types of palmitoleyl MTO (Pal-MTO) lipids: monopalmitoleyl MTO (mono-Pal-MTO) and dipalmitoleyl MTO (di-Pal-MTO). Among various lipid compositions of MTO, nanoparticles containing mono-Pal-MTO and di-Pal-MTO at a molar ratio of 1:1 (md11-Pal-MTO nanoparticles) showed the most efficient cellular delivery of siRNA, higher than that of Lipofectamine 2000. Delivery of red fluorescence protein-specific siRNA into B16F10-RFP cells using md11-Pal-MTO nanoparticles reduced the expression of RFP at both mRNA and protein levels, demonstrating silencing of the siRNA target gene. Moreover, delivery of Mcl-1-specific anticancer siRNA (siMcl-1) using md11-Pal-MTO enhanced antitumor activity in vitro, reducing tumor cell viability by 81% compared to a reduction of 68% following Lipofectamine 2000-mediated transfection of siMcl-1. Intratumoral administration of siMcl-1 using md11-Pal-MTO nanoparticles significantly inhibited tumor growth, reducing tumor size by 83% compared to untreated controls. Our results suggest the potential of md11-Pal-MTO multifunctional nanoparticles for co-delivery of anticancer siRNAs for effective combination therapy.

KW - Anticancer chemo-gene therapy

KW - Co-delivery

KW - Mitoxantrone

KW - Multifunctional nanoparticles

KW - SiRNA

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U2 - 10.1016/j.biomaterials.2011.09.017

DO - 10.1016/j.biomaterials.2011.09.017

M3 - Article

C2 - 21937102

AN - SCOPUS:80054060205

SN - 0142-9612

VL - 32

SP - 9785

EP - 9795

JO - Biomaterials

JF - Biomaterials

IS - 36

ER -

Cationic drug-derived nanoparticles for multifunctional delivery of anticancer siRNA

Abstract

Keywords

ASJC Scopus subject areas

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