RRC ID 67202
Author Mori T, Hazekawa M, Yoshida M, Nishinakagawa T, Uchida T, Ishibashi D.
Title Enhancing the anticancer efficacy of a LL-37 peptide fragment analog using peptide-linked PLGA conjugate micelles in tumor cells.
Journal Int J Pharm
Abstract LL-37, a well-known antimicrobial human peptide, is a cationic peptide that provides an important antimicrobial defense mechanism in damaged skin. Accumulating evidence indicates that LL-37 also displays an anticancer effect in colon cancer, gastric cancer, hematologic malignancy and oral squamous cell carcinoma. However, anticancer activity of LL-37 peptide fragment analogs has not been reported. Poor intercellular translocation may be one of the causes for this lack of observed anticancer activity. In this study, a LL-37 peptide fragment analog with cysteine at the N-terminus was conjugated with the biodegradable polymer, lactic acid/glycolic acid copolymer (PLGA), using the thiol group of cysteine. The purpose of this study was to improve the cell permeability of the peptide using a micellar system and then evaluate the anticancer activity. Cell proliferation, migration, and invasion assays were performed to evaluate the anticancer activity in four cancer cell lines with high metastasis, HM-1, B16/BL6, HeLa, and HepG2. The LL-37 fragment peptide analog-linked PLGA conjugate was shown to effectively inhibit cell proliferation, migration, and invasion and had increased cell permeability in all the cancer cell lines, compared with the peptide alone. These results suggested that LL-37 fragment peptide analog (CKR12)-linked PLGA conjugate micelles could be useful in the development of cancer therapeutics.
Volume 606
Pages 120891
Published 2021-9-5
DOI 10.1016/j.ijpharm.2021.120891
PII S0378-5173(21)00697-9
PMID 34324984
MeSH Anti-Infective Agents* Carcinoma, Squamous Cell* Cell Line, Tumor Humans Micelles Mouth Neoplasms* Peptide Fragments
IF 4.845
Human and Animal Cells OV2944-HM-1(RCB1483) B16/BL6(RCB2638)