Novel Class of Nanoparticle Drug Transporters Selectively Target Lung Cancer Cells

A novel class of nanoparticles is able to deliver siRNA-based drugs selectively to lung cancer cells without harming normal cells.

Conventional chemotherapeutic agents kill all rapidly dividing cells, which produces numerous harmful side effects. To develop a method for delivering chemotherapeutic drugs specifically to cancer cells, investigators at the University of Texas Southwestern Medical Center (Dallas, USA) worked with a unique pair of matched cancer/normal cell lines obtained from a single patient.

The investigators screened hundreds of nanoparticle (NP) polymers looking for those that would be taken up only by the cancer cell line while being excluded by the normal cells. They identified selective NPs that promoted rapid endocytosis into HCC4017 cancer cells, but were arrested at the membrane of HBEC30-KT normal cells. When injected into tumor xenografts in mice, these cancer-selective NPs were retained in tumors for over one week, whereas nonselective NPs were cleared within hours.

The nanoparticles were loaded with a siRNA drug. Small interfering RNAs (siRNAs) are a small noncoding family of 19- to 25-nucleotide RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and their targets.

Results published the September 12, 2016, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences revealed that the NPs improved siRNA-mediated cancer cell apoptosis and caused significant suppression of tumor growth. Selective NPs were also able to mediate gene silencing in xenograft and orthotopic tumors via i.v. injection or aerosol inhalation, respectively.

These results highlighted the observation that different cells responded differently to the same drug carrier, an important factor that should be considered in the design and evaluation of all NP carriers. Since no targeting ligands were required, these functional polyester NPs provided an alternative approach for selective drug delivery to tumor cells that may improve efficacy and reduce adverse side effects of cancer therapies.

"The discovery that nanoparticles can be selective to certain cells based only on their physical and chemical properties has profound implications for nanoparticle-based therapies because cell type specificity of drug carriers could alter patient outcomes in the clinic," said senior author Dr. Daniel Siegwart, assistant professor of biochemistry at the University of Texas Southwestern Medical Center. "At the same time, a deeper understanding of nanoparticle interactions in the body opens the door to predict patient responses to existing liposome and nanoparticle therapies, and offers the potential to create future drug carriers customized according to individual genetic profiles."

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University of Texas Southwestern Medical Center