Polymeric nano-micelles as novel cargo-carriers for LY2157299 liver cancer cells delivery

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Abstract

LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGFβ. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a “nano-elastic” carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA). PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF) have also been demonstrated.

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Hanafy, N. A. N., Quarta, A., Ferraro, M. M., Dini, L., Nobile, C., De Giorgi, M. L., … Leporatti, S. (2018). Polymeric nano-micelles as novel cargo-carriers for LY2157299 liver cancer cells delivery. International Journal of Molecular Sciences, 19(3). https://doi.org/10.3390/ijms19030748

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