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Therapeutic potential of a cell penetrating peptide (CPP, NP1) mediated siRNA delivery: Evidence in 3D spheroids of colon cancer cells
Author(s) -
AlHusaini Khalsa,
Elkamel Erij,
Han Xiaoxia,
Chen Pu
Publication year - 2020
Publication title -
the canadian journal of chemical engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.404
H-Index - 67
eISSN - 1939-019X
pISSN - 0008-4034
DOI - 10.1002/cjce.23743
Subject(s) - spheroid , transfection , gene knockdown , rna interference , apoptosis , in vitro , gene silencing , small interfering rna , cell penetrating peptide , cell , chemistry , microbiology and biotechnology , cancer research , cell culture , biology , rna , biochemistry , gene , genetics
RNA interference holds great potential for cancer therapeutics and its success is highly dependent on an effective delivery system. As most preclinical drug screening in vitro was conducted in flat monolayer cell cultures, development of more physiologically relevant models is needed to enhance testing reliability and effectiveness. Here, the aim was to develop 3D cell spheroids and evaluate the efficiency of NP1, a novel cell penetrating peptide, CPP (STR‐H16R8), developed by our group to assist siRNA delivery. NP1 elicited significant cellular uptake of siRNA and promoted great siRNA knockdown efficiency of Bcl‐2 and VEGF mRNA in 3D spheroids (53% and 51%, respectively), induced marked apoptosis after silencing HIF mRNA, and 3D spheroids displayed apoptosis resistance compared to 2D cells. Taken together, 3D spheroids provide an improved model for testing siRNA delivery and NP1 has proved to be a powerful in vitro transfection reagent.