Stapling of short cell-penetrating peptides for enhanced tumor cell-and-tissue dual-penetration.

Effective delivery of therapeutics to tumors is generally hampered by the limited penetration of biological barriers imposed by the tumor microenvironment. Despite the broad applications of cell-penetrating peptides (CPPs) for intracellular delivery of therapeutics across membrane bilayers, the discovery of novel CPPs with enhanced tumor tissue permeability remains largely unexplored. Herein, we identified two short stapled CPPs with aromatic cross-links that confer superior dual-penetration in tumor cells and tissues over their linear counterparts. This work may benefit the future applications of constrained CPPs as powerful molecular transporters to access deeper tumor tissues.

Rational Design of a Dual-Targeting Natural Toxin-Like Bicyclic Peptide for Selective Bioenergetic Blockage in Cancer Cells.

Stapled α-helical peptides emerge as one of the attractive peptidomimetics which can efficiently penetrate the cell membrane to access intracellular targets. However, the incorporation of a highly lipophilic cross-link may lead to nonspecific membrane toxicity in certain cases. Here, we report a new class of thioether-tethered bicyclic α-helical peptide to mimic the highly constrained loop-helix structure of natural toxins with the dual-targeting ability for both cell-surface receptors and intracellular targets. The thioether cross-links are introduced to replace the redox-sensitive disulfide bonds in natural toxins via a photoinduced thiol-yne reaction followed by macrolactamization. As a proof of concept, αVß3 integrin targeting ligand was grafted into one of the macrocycles in the bicyclic scaffold, while a mitochondria-targeting proapoptotic motif was introduced into the other macrocycle stabilized by an i, i + 7 alkyl thioether cross-link to recapitulate its α-helical conformation. The obtained dual-targeting bicyclic α-helical BIRK peptides showed highly stable α-helical conformation in the presence of denaturants or under high temperature. Notably, BIRK peptides could induce selective cell death in αVß3 integrin-positive B16F10 cells by interfering with the bioenergetic functions of mitochondria. This work provides a new avenue to design and stabilize α-helical peptides in a highly constrained bicyclic loop-helix scaffold with dual functionality.

Application of a social media platform as a patient reminder in the treatment of Helicobacter pylori.

BACKGROUND: To investigate the effect of a social media platform for the treatment of Helicobacter pylori infection. MATERIALS AND METHODS: We enrolled 222 patients from October 2018 to June 2019, who required H pylori therapy. We used WeChat, a social media platform, as a patient reminder tool. They were randomly divided into the intervention and control groups (n = 111 per group) to compare and evaluate their disease awareness, medication adherence, incidence of adverse drug reactions, and H pylori eradication rate. RESULTS: Patients in the intervention group had significantly better disease-related knowledge, medication adherence, and H pylori eradication rates than those in the control group (P < .05). CONCLUSIONS: Using a social media platform may improve treatment rates of H pylori infection.