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Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
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Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy

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Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for enhanced anticancer efficacy

Seung Hee Kang1, Hee-Jeong Cho, Gayong Shim

  • 1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-713, South Korea.

Pharmaceutical Research
|September 1, 2011
PubMed
Abstract

Insights

Co-delivery of small interfering RNA (siRNA) and a MEK inhibitor using cationic liposomes significantly enhanced anticancer activity. This combination therapy effectively reduced tumor cell survival and inhibited tumor growth in vivo.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Cancer Therapy

Background:

  • Cationic liposomes are promising drug delivery vehicles.
  • Combination therapy can overcome drug resistance and improve efficacy.

Purpose of the Study:

  • To evaluate the combined anticancer effects of siRNA and a MEK inhibitor delivered via cationic liposomes.
  • To assess the in vitro and in vivo efficacy of this co-delivery system.

Main Methods:

  • N',N''-dioleylglutamide-based cationic liposomes (DGL) were developed.
  • MEK inhibitor PD0325901 and Mcl1-specific siRNA (siMcl1) were co-delivered using PDGL.
  • In vitro cellular delivery, protein silencing, and tumor cell survival were assessed.
  • In vivo anticancer activity was evaluated in xenografted mice.

Main Results:

  • PDGL efficiently delivered siRNA and the MEK inhibitor into cancer cells.
  • Co-delivery reduced Mcl1 and pERK1/2 protein expression and enhanced tumor cell death.
  • In vivo, PDGL co-delivery inhibited tumor growth by 79% and induced significant apoptosis.

Conclusions:

  • Co-delivery of siMcl1 and PD0325901 via PDGL represents a potent combination chemogene therapy strategy.
  • This approach holds potential for enhanced cancer treatment.

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