SN-38 is an antineoplastic drug with a three orders of magnitude higher activity than its prodrug, irinotecan, a common chemotherapeutic of choice in the treatment of colorectal cancer. A considerable number of genes are known to alter their expression under the influence of free SN-38, but no studies have looked at the gene expression effects of SN-38 delivered via poly(D-L-lactide-co-caprolactone) (PLCL) nanoparticles yet.
We evaluated changes to expression levels of genes encoding for ubiquitin D (UBD), fibroblast growth factor 3 (FGF3), histone (HIST), and regulator of cell cycle (RGCC) in SW-480 colon cancer cells in response to free SN-38 and two types of poloxamer-coated PLCL (PEO-PPO-PEO/PLCL) nanoparticles as carriers for SN-38, containing different conformations of the hydrophilic stealth corona: dense or collapsed.
Both the free drug and the two drug-loaded nanoformulations upregulated UBD and RGCC and downregulated FGF3 and HIST, which was consistent with the pharmacological activity of SN-38. Still, there was a clear difference in gene expression levels in SW-480 cells depending on whether they were challenged with free SN-38 or with nanoparticles loaded with SN-38. Most critically, the delivery of SN-38 with the nanoparticles prolonged its mode of action and, in the case of genes such as UBD, FGF3, and HIST, provided for a more intense effect on gene expression alteration than that achieved by the drug alone.
Nanoparticles comprising the collapsed PEO-PPO-PEO corona produced a more intense effect on gene expression alteration than the nanoparticles with the dense PEO-PPO-PEO corona.
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Koliqi, R., Grapci, A.D., Selmani, P.B. et al. Gene Expression Effects of the Delivery of SN-38 via Poly(D-L-lactide-co-caprolactone) Nanoparticles Comprising Dense and Collapsed Poloxamer Coronae. J Pharm Innov 18, 585–593 (2023). https://doi.org/10.1007/s12247-022-09672-8