Journal
ADVANCED SCIENCE
Volume 10, Issue 11, Pages -Publisher
WILEY
DOI: 10.1002/advs.202207228
Keywords
cell membrane; nanofibers; peptide-conjugated probe; self-assemble; tumor metastasis
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A smart transformable peptide-conjugated probe (DMFA) is designed for treatment on the tumor cell membrane, which undergoes in situ morphological transformation upon enzyme cleavage. The probe self-assembles into nanoparticles and anchors on the cell membrane, and upon cleavage by matrix metalloproteinase-2, it forms alpha-helix and beta-sheet structures. The resulting cell membrane breakage and nanofibers wrapping the cells can inhibit the PI3K-Akt signaling pathway, leading to the inhibition of tumor cell growth and metastasis. This peptide-conjugated probe shows great potential in tumor therapy.
Despite the promising advancements of in situ forming nanoassembly for the inhibition of tumor growth and metastasis, the lack of sufficient triggering sites and hardly controlling the forming position restrict their further developments. Herein, a smart transformable peptide-conjugated probe (DMFA) with enzyme cleavage-induced morphological change is designed for treatment on the tumor cell membrane. Specifically, after self-assembling into nanoparticles and anchoring on the cell membrane with sufficient interaction sites rapidly and stably, DMFA will be efficiently cleaved into alpha-helix forming part (DP) and beta-sheet forming part (LFA) by overexpressed matrix metalloproteinase-2. Thus, the promoted Ca2+ influx by DP-induced cell membrane breakage and decreased Na+/K+-ATPase activity by LFA-assembled nanofibers wrapping the cells can inhibit PI3K-Akt signaling pathway, leading to the inhibition of tumor cell growth and metastasis. This peptide-conjugated probe undergoes in situ morphological transformation on the cell membrane, exhibiting great potential in tumor therapy.
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