In Vivo Self‐Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization

Abstract

Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes,whichisakey bottleneckinpeptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. Ap hosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK] 2 (K) and ar esponsive moiety phosphorylated Y( Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self-assembles in situ, whichinduces the aggregation of ALP and the protein-lipid phase separation on cell membrane.C onsequently,K Yp internalization is 2-fold enhanced compared to non-responsive peptide,and IC 50 value of KYp is approximately 5t imes lower than that of free peptide. Therefore,t he in vivo self-assembly induced phase separation on cell membrane promises anew strategy to improve the drug delivery efficacy in cancer therapy.

Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice

“…The permeability change of the cell membrane was investigated by measuring the leakage of the cytoplasmic enzyme lactate dehydrogenase (LDH) into the culture medium, an indicative assay of cell membrane permeability. 35 Aer treatment with CTxB, the percentage of released LDH increased from 11.5% to 15%. Upon activation by the HCR, the percentage of released LDH further increased to 32% (Fig.…”

Supramolecular Self‐Assembly in Living Cells

“…Ap eptide precursor containing aphosphate moiety is an amphiphilic molecule that undergoes ad ephosphorylation reaction and loses the phosphate group (water-soluble moiety), resulting in amore hydrophobic moiety that induces self-assembly process on/in cancer cells (Figure 6). [39] This strategy is widely used in various applications,such as cancer therapy,b ioimaging,e nhanced internalization of anticancer peptides, [40] and selective apoptosis of pluripotent stem cells (anti-iPSC agent). [41] Bortezomib (BTZ) is ap roteasome inhibitor for the treatment of myeloma.…”

Skin-like wound dressings with on-demand administration based onin situpeptide self-assembly for skin regeneration

“…15,16 Antibacterial peptides, 17,18 such as the (KLAKLAK) 2 peptide with an α-helix structure and amphiphilic molecule, 19–21 can bind to microbial membranes by electrostatic action and destroy the cell membrane physically. 22 Furthermore, silk fibroin (SF), a natural protein extracted from domestic silk with good biocompatibility and biodegradability, low immunogenicity and excellent processibility, is widely used in tissue engineering and biological medicine. 23,24 Owing to the similar Young's modulus to skin, SF has served as a skin-like biomimetic wound dressing to deliver antibacterial and bioactive agents for skin wound regeneration.…”