Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance

Olga B. Garbuzenko, Maha Saad, Vitaly P. Pozharov, Kenneth R. Reuhl, Gediminas Mainelis, Tamara Minko

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Development of cancer cell resistance, low accumulation of therapeutic drug in the lungs, and severe adverse treatment side effects represent main obstacles to efficient chemotherapy of lung cancer. To overcome these difficulties, we propose inhalation local delivery of anticancer drugs in combination with suppressors of pump and nonpump cellular resistance. To test this approach, nanoscale-based delivery systems containing doxorubicin as a cell death inducer, antisense oligonucleotides targeted to MRP1 mRNA as a suppressor of pump resistance and to BCL2 mRNA as a suppressor of nonpump resistance, were developed and examined on an orthotopic murine model of human lung carcinoma. The experimental results show high antitumor activity and low adverse side effects of proposed complex inhalatory treatment that cannot be achieved by individual components applied separately. The presentwork potentially contributes to the treatment of lung cancer by describing a unique combinatorial local inhalation delivery of drugs and suppressors of pump and nonpump cellular resistance.

Original languageEnglish (US)
Pages (from-to)10737-10742
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number23
DOIs
StatePublished - Jun 8 2010

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Antisense oligonucleotides
  • Inhalation
  • Liposomes
  • Orthotopic lung cancer model
  • Pump and nonpump resistance

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