Co-delivery of siRNA and etoposide to cancer cells using an MDEA esterquat based drug delivery system

Petya Georgieva Popova, Martine Notabi, Christian Code, Eva C. Arnspang, Morten Østergaard Andersen

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Abstract

Cancer has become the leading cause of death in many countries. Chemotherapy is a key component in the treatment of most cancers but has limited efficacy if the cancer develops resistance to the treatment over time and recur. RNA interference may be used to reduce the production of the proteins responsible for chemotherapeutic resistance. Small interfering RNAs (siRNA) may be used to induce RNA interference but the application of these to cancer cells is hampered by poor serum stability and delivery to their cytoplasmic site of activity. This work introduces a novel nanoparticle delivery system for siRNA and hydrophobic anticancer drugs. The system is based on a cationic MDEA esterquat, which is widely and safely used in personal care products but has never been assessed for drug delivery applications. We show that MDEA forms spherical compact nanoparticles when combined with siRNA that delivers the siRNA to cancer cells where it induces gene silencing. By combining DOPE and MDEA in ratios of 2:1 and 3:1, even higher gene silencing levels (>90%) may be achieved. The system is capable of combinational therapy by co-delivering siRNA and the chemotherapeutic drug etoposide to cancer cells and these particles both induce gene silencing and chemotherapy induced cell death. We believe the present system may be used for intra-tumoral injection of chemotherapy in solid chemotherapy resistant tumors and for systemic delivery with further development.
Original languageEnglish
JournalEuropean Journal of Pharmaceutical Sciences
Volume127
Pages (from-to)142-150
ISSN0928-0987
DOIs
Publication statusPublished - Jan 2019

Fingerprint

Etoposide
Small Interfering RNA
Neoplasms
RNA Interference
Pharmaceutical Preparations
3,4-methylenedioxyethamphetamine
Cause of Death
Cell Death
Serum
Proteins

Keywords

  • Cancer
  • DOPE
  • Etoposide
  • MDEA
  • Nanoparticles
  • RNA interference
  • siRNA

Cite this

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title = "Co-delivery of siRNA and etoposide to cancer cells using an MDEA esterquat based drug delivery system",
abstract = "Cancer has become the leading cause of death in many countries. Chemotherapy is a key component in the treatment of most cancers but has limited efficacy if the cancer develops resistance to the treatment over time and recur. RNA interference may be used to reduce the production of the proteins responsible for chemotherapeutic resistance. Small interfering RNAs (siRNA) may be used to induce RNA interference but the application of these to cancer cells is hampered by poor serum stability and delivery to their cytoplasmic site of activity. This work introduces a novel nanoparticle delivery system for siRNA and hydrophobic anticancer drugs. The system is based on a cationic MDEA esterquat, which is widely and safely used in personal care products but has never been assessed for drug delivery applications. We show that MDEA forms spherical compact nanoparticles when combined with siRNA that delivers the siRNA to cancer cells where it induces gene silencing. By combining DOPE and MDEA in ratios of 2:1 and 3:1, even higher gene silencing levels (>90{\%}) may be achieved. The system is capable of combinational therapy by co-delivering siRNA and the chemotherapeutic drug etoposide to cancer cells and these particles both induce gene silencing and chemotherapy induced cell death. We believe the present system may be used for intra-tumoral injection of chemotherapy in solid chemotherapy resistant tumors and for systemic delivery with further development.",
keywords = "Cancer, DOPE, Etoposide, MDEA, Nanoparticles, RNA interference, siRNA",
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Co-delivery of siRNA and etoposide to cancer cells using an MDEA esterquat based drug delivery system. / Popova, Petya Georgieva; Notabi, Martine; Code, Christian ; Arnspang, Eva C.; Andersen, Morten Østergaard.

In: European Journal of Pharmaceutical Sciences, Vol. 127, 01.2019, p. 142-150.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Co-delivery of siRNA and etoposide to cancer cells using an MDEA esterquat based drug delivery system

AU - Popova, Petya Georgieva

AU - Notabi, Martine

AU - Code, Christian

AU - Arnspang, Eva C.

AU - Andersen, Morten Østergaard

PY - 2019/1

Y1 - 2019/1

N2 - Cancer has become the leading cause of death in many countries. Chemotherapy is a key component in the treatment of most cancers but has limited efficacy if the cancer develops resistance to the treatment over time and recur. RNA interference may be used to reduce the production of the proteins responsible for chemotherapeutic resistance. Small interfering RNAs (siRNA) may be used to induce RNA interference but the application of these to cancer cells is hampered by poor serum stability and delivery to their cytoplasmic site of activity. This work introduces a novel nanoparticle delivery system for siRNA and hydrophobic anticancer drugs. The system is based on a cationic MDEA esterquat, which is widely and safely used in personal care products but has never been assessed for drug delivery applications. We show that MDEA forms spherical compact nanoparticles when combined with siRNA that delivers the siRNA to cancer cells where it induces gene silencing. By combining DOPE and MDEA in ratios of 2:1 and 3:1, even higher gene silencing levels (>90%) may be achieved. The system is capable of combinational therapy by co-delivering siRNA and the chemotherapeutic drug etoposide to cancer cells and these particles both induce gene silencing and chemotherapy induced cell death. We believe the present system may be used for intra-tumoral injection of chemotherapy in solid chemotherapy resistant tumors and for systemic delivery with further development.

AB - Cancer has become the leading cause of death in many countries. Chemotherapy is a key component in the treatment of most cancers but has limited efficacy if the cancer develops resistance to the treatment over time and recur. RNA interference may be used to reduce the production of the proteins responsible for chemotherapeutic resistance. Small interfering RNAs (siRNA) may be used to induce RNA interference but the application of these to cancer cells is hampered by poor serum stability and delivery to their cytoplasmic site of activity. This work introduces a novel nanoparticle delivery system for siRNA and hydrophobic anticancer drugs. The system is based on a cationic MDEA esterquat, which is widely and safely used in personal care products but has never been assessed for drug delivery applications. We show that MDEA forms spherical compact nanoparticles when combined with siRNA that delivers the siRNA to cancer cells where it induces gene silencing. By combining DOPE and MDEA in ratios of 2:1 and 3:1, even higher gene silencing levels (>90%) may be achieved. The system is capable of combinational therapy by co-delivering siRNA and the chemotherapeutic drug etoposide to cancer cells and these particles both induce gene silencing and chemotherapy induced cell death. We believe the present system may be used for intra-tumoral injection of chemotherapy in solid chemotherapy resistant tumors and for systemic delivery with further development.

KW - Cancer

KW - DOPE

KW - Etoposide

KW - MDEA

KW - Nanoparticles

KW - RNA interference

KW - siRNA

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DO - 10.1016/j.ejps.2018.10.023

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