Journal
BIOMATERIALS SCIENCE
Volume 9, Issue 23, Pages -Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1bm00819f
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Funding
- National Research Foundation of Korea of the South Korean government (the Ministry of Science and ICT) [NRF-2017M3A9E4077448, NRF-2020R1F1A1048296, NRF-2021R1F1A1061286]
- National Research Foundation of Korea [2017M3A9E4077448] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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A novel cell penetrating peptide system has been developed with high selectivity and penetrability for HER2-overexpressing cancer cells, showcasing potential as a new approach for cancer therapy.
We have developed a cell penetrating peptide (CPP) system with high selectivity and penetrability at nanomolar concentrations with a combination of an HER2-selective affibody, Z(HER2:342) (Z(HER2)), and a dimeric alpha-helical leucine- and lysine-rich peptide, LK-2. Z(HER2) and LK-2 are linearly fused together and expressed in a prokaryotic system to create the LK-2-Z(HER2) protein, which can successfully distinguish and penetrate HER2-overexpressing cancer cells at nanomolar concentrations. LK-2-Z(HER2) has the ability to intracellularly deliver doxorubicin as a conjugate form to enhance its anti-cancer effect on HER2-overexpressing breast cancer cells with a great selectivity. The selective penetrability was confirmed in vitro, in 3D spheroids, and in in vivo models. LK-2-Z(HER2) has the capability to overcome the weak points of current CPPs, such as poor penetrability at low concentrations and a lack of selectivity, by combining powerful CPP and affibody sequences.
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