TY - JOUR
T1 - Rationally Designed Enzyme-Resistant Peptidic Assemblies for Plasma Membrane Targeting in Cancer Treatment
AU - Zhang, Shijin
AU - Gong, Xuewen
AU - Wei, Qinchuan
AU - Lv, Jiarong
AU - Du, Enming
AU - Wang, Jiaqing
AU - Ji, Wei
AU - Li, Ji Liang
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/8/21
Y1 - 2023/8/21
N2 - 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.
AB - 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.
KW - enzyme resistance
KW - extrinsic apoptosis pathways
KW - plasma membranes
KW - self-assembling peptides
KW - stress actin fibers
UR - http://www.scopus.com/inward/record.url?scp=85164585220&partnerID=8YFLogxK
U2 - 10.1002/adhm.202301730
DO - 10.1002/adhm.202301730
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C2 - 37400071
AN - SCOPUS:85164585220
SN - 2192-2640
VL - 12
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 21
M1 - 2301730
ER -
