Researchers at the Harold C. Simmons Comprehensive Cancer Center (TX, USA) have developed a synthetic polymer for transporting drugs into lung cancer cells without affecting healthy cells. Details appeared recently in the Proceedings of the National Academy of Sciences.
“The discovery that nanoparticles (NPs) can be selective to certain cells based only on their physical and chemical properties has profound implications for NP-based therapies because cell type specificity of drug carriers could alter patient outcomes in the clinic,” commented corresponding author Daniel Siegwart (University of Texas Southwestern Medical Center, TX, USA).
Using high-throughput screening, the Texas team examined many different types of polymers, and concluded that cells responded differently to the same drug carrier, even when the cancerous and healthy cells were isolated from the same patient.
Using selective polyplex NPs, cancer cells (HCC4017) rapidly disintegrated via endocytosis, but were arrested at the cell membrane of HBEC30-KT normal cells. Cancer-selective NPs were retained for up to 1 week in tumor xenograft mice, encouraging siRNA-mediated cancer cell apoptosis and tumor suppression. Nonselective control NPs were cleared within hours.
“The ability to specifically target cancer cells using NPs could alter how we administer drugs to patients,” noted author John Minna (Harold C. Simmons Comprehensive Cancer Center).
Selective NPs were also able to mediate gene silencing when injected intravenously with or via inhalation in both xenograft and orthotopic tumors.
Most importantly, this research highlights how different cells respond differently to the same drug carrier, which should be taken into account when designing NP carriers. NPs could also potentially be used as an alternative approach for selective drug delivery to tumor cells thus improving efficacy and reducing adverse effects.
Sources: Yan Y, Xiong H, Miller JB et al. Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells. Proc. Natl Acad. Sci. USA. DOI:10.1073/pnas.1606886113 (2016) (Epub ahead of print); University of Texas Southwestern Medical Center press release