Inhaled Nanoparticles Bombard Lung Tumors with Anticancer Drugs and siRNAs

A novel nanoparticle delivery system optimized for inhalation combines anticancer drugs with small interfering RNAs (siRNA), which suppress the ability of cancer cells to develop drug resistance.

A major drawback to conventional chemotherapy for lung cancer is that the drugs tend to accumulate in the liver, kidney, and spleen, with only low concentrations of the drugs ever making it to the lungs. To correct this situation, investigators at Oregon State University (Corvallis, USA) developed a new drug delivery system optimized for inhalation directly to the site of lung tumors.

The system described in the May 3, 2013, online edition of the Journal of Controlled Release comprised: (1) nanostructured lipid carriers (NLC); (2) an anticancer drug (doxorubicin or paclitaxel); (3) an siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) an siRNA targeted to Bcl-2 mRNA as a suppressor of nonpump cellular resistance; and (5) a modified synthetic analog of luteinizing hormone releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells.

The NLCS system was tested in vitro using human lung cancer cells and in vivo utilizing a mouse model of human lung cancer. After inhalation, the NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact. The inhalation approach significantly decreased the exposure of healthy organs to the chemotherapeutic drugs when compared with intravenous injection.

The NLCS showed enhanced antitumor activity when compared with intravenous treatment, as the amount of the drug delivered to the lungs by inhalation was 83% as compared to only 23% by injection.

“Lung cancer damage is usually not localized, which makes chemotherapy an important part of treatment,” said first author Dr. Oleh Taratula, assistant professor of pharmacy at Oregon State University. “However, the drugs used are toxic and can cause organ damage and severe side effects if given conventionally through intravenous administration. A drug delivery system that can be inhaled is a much more efficient approach, targeting just the cancer cells as much as possible. Other chemotherapeutic approaches only tend to suppress tumors, but this system appears to eliminate it.”

While patent protection is being sought to protect NLCS technology, considerably more testing will be required before it is ready for human clinical trials.


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