Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer

Soo Hyun Jang; Su Jin Choi; Ji Hyun Oh; Song Wha Chae; Kihoon Nam; Jong Sang Park; Hwa Jeong Lee

doi:10.3109/03639045.2010.489563

Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer

Soo Hyun Jang, Su Jin Choi, Ji Hyun Oh, Song Wha Chae, Kihoon Nam, Jong Sang Park, Hwa Jeong Lee

Department of Pharmaceutical Sciences

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

21 Scopus citations

Abstract

Background: A specific and effective strategy is in demand to treat ovarian cancer successfully. Epidermal growth factor receptor (EGFR) is highly expressed in ovarian cancer, and thus EGFR antisense gene therapy can be a potential therapeutic strategy. Method: l-Arginine-grafted-polyamidoamine dendrimer (PAMAM-Arg) has been reported to be a novel nonviral gene delivery carrier. Therefore, the ability of PAMAM-Arg in transferring a luciferase gene to ovarian carcinoma SK-OV3 cells has been examined, and the cytotoxicity of the cationic polymer has been investigated. In addition, the suppression of cell proliferation has been evaluated by transferring an EGFR antisense gene to SK-OV3 cells using PAMAM-Arg. Polyethyleneimine (PEI) 25K was used as a positive control. Results: As a result, in vitro gene transfection efficiency of PAMAM-Arg was enhanced with increasing transfection time and NP ratios. PAMAM-Arg transferred the luciferase gene into cells more efficiently than PEI. In addition, PAMAM-Arg was minimally toxic to the cells whereas PEI 25K was highly toxic. The polyplexes formed by the EGFR antisense gene and PAMAM-Arg significantly reduced thymidine incorporation into the cells suggesting the suppression of cancer cell proliferation. Conclusion: These results suggest that a PAMAM-ArgEGFR antisense gene complex can be used as a safe and efficient therapeutic agent for cancer gene therapy.

Original language	English
Pages (from-to)	41-46
Number of pages	6
Journal	Drug Development and Industrial Pharmacy
Volume	37
Issue number	1
DOIs	https://doi.org/10.3109/03639045.2010.489563
State	Published - Jan 2011

Bibliographical note

Funding Information:
This work was supported by the second stage of Brain Korea 21 program, the National Research Foundation (NRF) of Korea Grant funded by the Korean Government (2007-0055790), and grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Education, Science & Technology (MEST), and the NRF of Korea through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

Keywords

Antisense gene
Cancer gene therapy
Epidermal growth factor receptor
L-arginine-grafted-polyamidoamine dendrimer
Polyethyleneimine
Thymidine incorporation

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10.3109/03639045.2010.489563

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title = "Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer",

abstract = "Background: A specific and effective strategy is in demand to treat ovarian cancer successfully. Epidermal growth factor receptor (EGFR) is highly expressed in ovarian cancer, and thus EGFR antisense gene therapy can be a potential therapeutic strategy. Method: l-Arginine-grafted-polyamidoamine dendrimer (PAMAM-Arg) has been reported to be a novel nonviral gene delivery carrier. Therefore, the ability of PAMAM-Arg in transferring a luciferase gene to ovarian carcinoma SK-OV3 cells has been examined, and the cytotoxicity of the cationic polymer has been investigated. In addition, the suppression of cell proliferation has been evaluated by transferring an EGFR antisense gene to SK-OV3 cells using PAMAM-Arg. Polyethyleneimine (PEI) 25K was used as a positive control. Results: As a result, in vitro gene transfection efficiency of PAMAM-Arg was enhanced with increasing transfection time and NP ratios. PAMAM-Arg transferred the luciferase gene into cells more efficiently than PEI. In addition, PAMAM-Arg was minimally toxic to the cells whereas PEI 25K was highly toxic. The polyplexes formed by the EGFR antisense gene and PAMAM-Arg significantly reduced thymidine incorporation into the cells suggesting the suppression of cancer cell proliferation. Conclusion: These results suggest that a PAMAM-ArgEGFR antisense gene complex can be used as a safe and efficient therapeutic agent for cancer gene therapy.",

keywords = "Antisense gene, Cancer gene therapy, Epidermal growth factor receptor, L-arginine-grafted-polyamidoamine dendrimer, Polyethyleneimine, Thymidine incorporation",

author = "Jang, {Soo Hyun} and Choi, {Su Jin} and Oh, {Ji Hyun} and Chae, {Song Wha} and Kihoon Nam and Park, {Jong Sang} and Lee, {Hwa Jeong}",

note = "Funding Information: This work was supported by the second stage of Brain Korea 21 program, the National Research Foundation (NRF) of Korea Grant funded by the Korean Government (2007-0055790), and grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Education, Science & Technology (MEST), and the NRF of Korea through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.",

year = "2011",

month = jan,

doi = "10.3109/03639045.2010.489563",

language = "English",

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AU - Jang, Soo Hyun

AU - Choi, Su Jin

AU - Oh, Ji Hyun

AU - Chae, Song Wha

AU - Nam, Kihoon

AU - Park, Jong Sang

AU - Lee, Hwa Jeong

N1 - Funding Information: This work was supported by the second stage of Brain Korea 21 program, the National Research Foundation (NRF) of Korea Grant funded by the Korean Government (2007-0055790), and grant No. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Education, Science & Technology (MEST), and the NRF of Korea through the Center for Cell Signaling & Drug Discovery Research at Ewha Womans University. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this paper.

PY - 2011/1

Y1 - 2011/1

N2 - Background: A specific and effective strategy is in demand to treat ovarian cancer successfully. Epidermal growth factor receptor (EGFR) is highly expressed in ovarian cancer, and thus EGFR antisense gene therapy can be a potential therapeutic strategy. Method: l-Arginine-grafted-polyamidoamine dendrimer (PAMAM-Arg) has been reported to be a novel nonviral gene delivery carrier. Therefore, the ability of PAMAM-Arg in transferring a luciferase gene to ovarian carcinoma SK-OV3 cells has been examined, and the cytotoxicity of the cationic polymer has been investigated. In addition, the suppression of cell proliferation has been evaluated by transferring an EGFR antisense gene to SK-OV3 cells using PAMAM-Arg. Polyethyleneimine (PEI) 25K was used as a positive control. Results: As a result, in vitro gene transfection efficiency of PAMAM-Arg was enhanced with increasing transfection time and NP ratios. PAMAM-Arg transferred the luciferase gene into cells more efficiently than PEI. In addition, PAMAM-Arg was minimally toxic to the cells whereas PEI 25K was highly toxic. The polyplexes formed by the EGFR antisense gene and PAMAM-Arg significantly reduced thymidine incorporation into the cells suggesting the suppression of cancer cell proliferation. Conclusion: These results suggest that a PAMAM-ArgEGFR antisense gene complex can be used as a safe and efficient therapeutic agent for cancer gene therapy.

AB - Background: A specific and effective strategy is in demand to treat ovarian cancer successfully. Epidermal growth factor receptor (EGFR) is highly expressed in ovarian cancer, and thus EGFR antisense gene therapy can be a potential therapeutic strategy. Method: l-Arginine-grafted-polyamidoamine dendrimer (PAMAM-Arg) has been reported to be a novel nonviral gene delivery carrier. Therefore, the ability of PAMAM-Arg in transferring a luciferase gene to ovarian carcinoma SK-OV3 cells has been examined, and the cytotoxicity of the cationic polymer has been investigated. In addition, the suppression of cell proliferation has been evaluated by transferring an EGFR antisense gene to SK-OV3 cells using PAMAM-Arg. Polyethyleneimine (PEI) 25K was used as a positive control. Results: As a result, in vitro gene transfection efficiency of PAMAM-Arg was enhanced with increasing transfection time and NP ratios. PAMAM-Arg transferred the luciferase gene into cells more efficiently than PEI. In addition, PAMAM-Arg was minimally toxic to the cells whereas PEI 25K was highly toxic. The polyplexes formed by the EGFR antisense gene and PAMAM-Arg significantly reduced thymidine incorporation into the cells suggesting the suppression of cancer cell proliferation. Conclusion: These results suggest that a PAMAM-ArgEGFR antisense gene complex can be used as a safe and efficient therapeutic agent for cancer gene therapy.

KW - Antisense gene

KW - Cancer gene therapy

KW - Epidermal growth factor receptor

KW - L-arginine-grafted-polyamidoamine dendrimer

KW - Polyethyleneimine

KW - Thymidine incorporation

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M3 - Article

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AN - SCOPUS:78649986679

SN - 0363-9045

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SP - 41

EP - 46

JO - Drug Development and Industrial Pharmacy

JF - Drug Development and Industrial Pharmacy

IS - 1

ER -

Nonviral gene delivery to human ovarian cancer cells using arginine-grafted PAMAM dendrimer

Abstract

Bibliographical note

Keywords

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