Bacterial tRNase–Based Gene Therapy with Poly(β-Amino Ester) Nanoparticles for Suppressing Melanoma Tumor Growth and Relapse

Sungjin Min, Yoonhee Jin, Chen Yuan Hou, Jayoung Kim, Jordan J. Green, Taek Jin Kang, Seung Woo Cho

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Here, a novel anticancer gene therapy with a bacterial tRNase gene, colicin D or virulence associated protein C (VapC), is suggested using biodegradable polymeric nanoparticles, such as poly(β-amino esters) (PBAEs) as carriers. These genes are meticulously selected, aiming at inhibiting translation in the recipients by hydrolyzing specific tRNA species. In terms of nanoparticles, out of 9 PBAE formulations, a leading polymer, (polyethylene oxide)4-bis-amine end-capped poly(1,4-butanediol diacrylate-co-5-amino-1-pentanol) (B4S5E5), is identified that displays higher gene delivery efficacy to cancer cells compared with the leading commercial reagent Lipofectamine 2000. Interestingly, the B4S5E5 PBAE nanoparticles complexed with colicin D or VapC plasmid DNA induce significant toxicity highly specific to cancer cells by triggering apoptosis. In contrast, the PBAE nanoparticles do not induce these cytotoxic effects in noncancerous cells. In a mouse melanoma model of grafted murine B16-F10 cells, it is demonstrated that treatment with PBAE nanoparticles complexed with these tRNase genes significantly reduces tumor growth rate and delays tumor relapse. Moreover, increased stability of PBAE by PEGylation further enhances the therapeutic effect of tRNase gene treatment and improves survival of animals. This study highlights a nonviral gene therapy that is highly promising for the treatment of cancer.

Original languageEnglish
Article number1800052
JournalAdvanced Healthcare Materials
Volume7
Issue number16
DOIs
Publication statusPublished - 2018 Aug 22

Fingerprint

Bacterial Genes
Gene therapy
Genetic Therapy
Nanoparticles
Tumors
Melanoma
Esters
Genes
Recurrence
Colicins
Growth
Neoplasms
Protein C
Virulence
Cells
Proteins
Therapeutic Uses
Cell death
Transfer RNA
Polyethylene oxides

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Min, Sungjin ; Jin, Yoonhee ; Hou, Chen Yuan ; Kim, Jayoung ; Green, Jordan J. ; Kang, Taek Jin ; Cho, Seung Woo. / Bacterial tRNase–Based Gene Therapy with Poly(β-Amino Ester) Nanoparticles for Suppressing Melanoma Tumor Growth and Relapse. In: Advanced Healthcare Materials. 2018 ; Vol. 7, No. 16.
@article{7d057329ed36450ba2232ebf909fc5b3,
title = "Bacterial tRNase–Based Gene Therapy with Poly(β-Amino Ester) Nanoparticles for Suppressing Melanoma Tumor Growth and Relapse",
abstract = "Here, a novel anticancer gene therapy with a bacterial tRNase gene, colicin D or virulence associated protein C (VapC), is suggested using biodegradable polymeric nanoparticles, such as poly(β-amino esters) (PBAEs) as carriers. These genes are meticulously selected, aiming at inhibiting translation in the recipients by hydrolyzing specific tRNA species. In terms of nanoparticles, out of 9 PBAE formulations, a leading polymer, (polyethylene oxide)4-bis-amine end-capped poly(1,4-butanediol diacrylate-co-5-amino-1-pentanol) (B4S5E5), is identified that displays higher gene delivery efficacy to cancer cells compared with the leading commercial reagent Lipofectamine 2000. Interestingly, the B4S5E5 PBAE nanoparticles complexed with colicin D or VapC plasmid DNA induce significant toxicity highly specific to cancer cells by triggering apoptosis. In contrast, the PBAE nanoparticles do not induce these cytotoxic effects in noncancerous cells. In a mouse melanoma model of grafted murine B16-F10 cells, it is demonstrated that treatment with PBAE nanoparticles complexed with these tRNase genes significantly reduces tumor growth rate and delays tumor relapse. Moreover, increased stability of PBAE by PEGylation further enhances the therapeutic effect of tRNase gene treatment and improves survival of animals. This study highlights a nonviral gene therapy that is highly promising for the treatment of cancer.",
author = "Sungjin Min and Yoonhee Jin and Hou, {Chen Yuan} and Jayoung Kim and Green, {Jordan J.} and Kang, {Taek Jin} and Cho, {Seung Woo}",
year = "2018",
month = "8",
day = "22",
doi = "10.1002/adhm.201800052",
language = "English",
volume = "7",
journal = "Advanced healthcare materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",
number = "16",

}

Bacterial tRNase–Based Gene Therapy with Poly(β-Amino Ester) Nanoparticles for Suppressing Melanoma Tumor Growth and Relapse. / Min, Sungjin; Jin, Yoonhee; Hou, Chen Yuan; Kim, Jayoung; Green, Jordan J.; Kang, Taek Jin; Cho, Seung Woo.

In: Advanced Healthcare Materials, Vol. 7, No. 16, 1800052, 22.08.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bacterial tRNase–Based Gene Therapy with Poly(β-Amino Ester) Nanoparticles for Suppressing Melanoma Tumor Growth and Relapse

AU - Min, Sungjin

AU - Jin, Yoonhee

AU - Hou, Chen Yuan

AU - Kim, Jayoung

AU - Green, Jordan J.

AU - Kang, Taek Jin

AU - Cho, Seung Woo

PY - 2018/8/22

Y1 - 2018/8/22

N2 - Here, a novel anticancer gene therapy with a bacterial tRNase gene, colicin D or virulence associated protein C (VapC), is suggested using biodegradable polymeric nanoparticles, such as poly(β-amino esters) (PBAEs) as carriers. These genes are meticulously selected, aiming at inhibiting translation in the recipients by hydrolyzing specific tRNA species. In terms of nanoparticles, out of 9 PBAE formulations, a leading polymer, (polyethylene oxide)4-bis-amine end-capped poly(1,4-butanediol diacrylate-co-5-amino-1-pentanol) (B4S5E5), is identified that displays higher gene delivery efficacy to cancer cells compared with the leading commercial reagent Lipofectamine 2000. Interestingly, the B4S5E5 PBAE nanoparticles complexed with colicin D or VapC plasmid DNA induce significant toxicity highly specific to cancer cells by triggering apoptosis. In contrast, the PBAE nanoparticles do not induce these cytotoxic effects in noncancerous cells. In a mouse melanoma model of grafted murine B16-F10 cells, it is demonstrated that treatment with PBAE nanoparticles complexed with these tRNase genes significantly reduces tumor growth rate and delays tumor relapse. Moreover, increased stability of PBAE by PEGylation further enhances the therapeutic effect of tRNase gene treatment and improves survival of animals. This study highlights a nonviral gene therapy that is highly promising for the treatment of cancer.

AB - Here, a novel anticancer gene therapy with a bacterial tRNase gene, colicin D or virulence associated protein C (VapC), is suggested using biodegradable polymeric nanoparticles, such as poly(β-amino esters) (PBAEs) as carriers. These genes are meticulously selected, aiming at inhibiting translation in the recipients by hydrolyzing specific tRNA species. In terms of nanoparticles, out of 9 PBAE formulations, a leading polymer, (polyethylene oxide)4-bis-amine end-capped poly(1,4-butanediol diacrylate-co-5-amino-1-pentanol) (B4S5E5), is identified that displays higher gene delivery efficacy to cancer cells compared with the leading commercial reagent Lipofectamine 2000. Interestingly, the B4S5E5 PBAE nanoparticles complexed with colicin D or VapC plasmid DNA induce significant toxicity highly specific to cancer cells by triggering apoptosis. In contrast, the PBAE nanoparticles do not induce these cytotoxic effects in noncancerous cells. In a mouse melanoma model of grafted murine B16-F10 cells, it is demonstrated that treatment with PBAE nanoparticles complexed with these tRNase genes significantly reduces tumor growth rate and delays tumor relapse. Moreover, increased stability of PBAE by PEGylation further enhances the therapeutic effect of tRNase gene treatment and improves survival of animals. This study highlights a nonviral gene therapy that is highly promising for the treatment of cancer.

UR - http://www.scopus.com/inward/record.url?scp=85051863521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051863521&partnerID=8YFLogxK

U2 - 10.1002/adhm.201800052

DO - 10.1002/adhm.201800052

M3 - Article

C2 - 29888531

AN - SCOPUS:85051863521

VL - 7

JO - Advanced healthcare materials

JF - Advanced healthcare materials

SN - 2192-2640

IS - 16

M1 - 1800052

ER -