An in vitro investigation of a detachable fork-like structure as efficient nuclear-targeted sub-unit in A2780 cell cultures

International Journal of Pharmaceutics
Shan GuanYuan Huang

Abstract

The pharmacological target of many anticancer drugs is those molecules associated with genetic information which are localized in nucleus. To efficiently deliver drugs into cancer cell nucleus, in our previous study, a fork-like sub-unit, with one end conjugated with a targeting peptide named R8NLS (CRRRRRRRRPKKKRKV) and the other end conjugated with c-Myc oncogene inhibitor H1-S6A,F8A (H1) peptide, was linked onto the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via an enzyme degradable glycylphenylalanylleucylglycine (GFLG) tetrapeptide spacer. Here, an in vitro mechanism investigation of the fork-like sub-unit was studied in detail. We found that the fusion with two complementary R8 and NLS motifs is required to exert the multifunctional targeting capability of the tandem R8NLS peptide in overcoming various intracellular barriers, including enhancing cellular uptake, facilitating endosomal escape and penetrating through the double-layered nuclear membrane. Also required is the tactful detachment of the fork-like sub-unit from the copolymer in response to intracellular stimulus, because a smaller sub-unit not only increases the intracellular trafficking efficiency by reducing the size burden of magical bullet R8NLS, but...Continue Reading

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Citations

Sep 14, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zhou ZhouYuan Huang
Feb 9, 2021·International Journal of Pharmaceutics·Diana CostaAna Figueiras
Mar 17, 2020·International Journal of Pharmaceutics·Dandan XieYuan Huang

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