Background/Aim: Developments in imaging have improved cancer diagnosis, but identification of malignant cells during surgical resection remains a challenge. The aim of this study was to investigate the pacifastin family of peptides for novel activity targeting tumor cells and the delivery of either imaging or therapeutic agents. Materials and Methods: Variants of pacifastin family peptides were generated, chemically modified and tested in human tumor xenografts. Results: A tumor-homing peptide-dye conjugate (THP1) accumulated in tumors in vivo and was internalized into cells. Examination of related peptides revealed residues critical for accumulation and allowed the engineering of improved tumor-targeting variants. A THP1-drug conjugate carrying the microtubule inhibitor, MMAE, showed limited activity in vitro and no difference compared to vehicle control in vivo. Conclusion: Although there are some obstacles to developing pacifastin-derived peptides for therapeutic activity, these optimized peptides have great promise for cancer imaging.
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