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A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer
Published on: September 13, 2022
Rationally Designed Enzyme-Resistant Peptidic Assemblies for Plasma Membrane Targeting in Cancer Treatment
Shijin Zhang1, Xuewen Gong1, Qinchuan Wei1
1National Engineering Research Centre of Ophthalmology and Optometry, School of Biomedical Engineering, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
Abstract:
Peptides are being increasingly important for subcellular targeted cancer treatment to improve specificity and reverse multidrug resistance. However, there has been yet any report on targeting plasma membrane (PM) through self-assembling peptides. A simple synthetic peptidic molecule (tF4) is developed. It is revealed that tF4 is carboxyl esterase-resistant and self-assembles into vesical nanostructures. Importantly, tF4 assemblies interact with PM through orthogonal hydrogen bonding and hydrophobic interaction to regulate cancer cellular functions. Mechanistically, tF4 assemblies induce stress fiber formation, cytoskeleton reconstruction, and death receptor 4/5 (DR4/5) expression in cancer cells. DR4/5 triggers extrinsic caspase-8 signaling cascade, resulting in cell death. The results provide a new strategy for developing enzyme-resistant and PM-targeting peptidic molecules against cancer.
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