Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer

Nanomedicine (Lond). 2008 Dec;3(6):761-76. doi: 10.2217/17435889.3.6.761.

Abstract

Aims: To develop a novel nanomedicine approach for the treatment of multidrug-resistant (MDR) cancer by combining an anticancer drug and suppressors of cellular resistance within one multifunctional nanocarrier-based delivery system (NDS).

Materials & methods: The NDS consisted of cationic liposomes (carrier, 100-140 nm), doxorubicin (DOX, anticancer drug), siRNA targeted to MRP1 and BCL2 mRNA (suppressors of pump and nonpump cellular-resistance, respectively). The resulting approximately 500 nm complex has a zeta potential of +4 mV.

Results & discussion: The NDS provides an effective co-delivery of DOX and siRNA as well as cell-death induction and suppression of cellular resistance in MDR lung cancer cells.

Conclusion: We demonstrate NDS-enhanced efficiency of chemotherapy to a level that cannot be achieved by applying its components separately.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Doxorubicin / administration & dosage
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Drug Resistance, Neoplasm*
  • Humans
  • Liposomes / chemistry
  • Multidrug Resistance-Associated Proteins / metabolism
  • Nanoparticles / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Multidrug Resistance-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA, Small Interfering
  • Doxorubicin
  • multidrug resistance-associated protein 1