1.0Future News 24https://futurenews24.comFuture News 24https://futurenews24.com/index.php/author/mridulpahuja20/rich600338<blockquote class="wp-embedded-content" data-secret="DdS0vnNL4m"><a href="https://futurenews24.com/index.php/2026/06/16/s41428-026-01212-2/">pH-responsive amphiphilic peptide nanofibers facilitate endosomal escape for cytosolic protein supply</a></blockquote><iframe sandbox="allow-scripts" security="restricted" src="https://futurenews24.com/index.php/2026/06/16/s41428-026-01212-2/embed/#?secret=DdS0vnNL4m" width="600" height="338" title="“pH-responsive amphiphilic peptide nanofibers facilitate endosomal escape for cytosolic protein supply” — Future News 24" data-secret="DdS0vnNL4m" frameborder="0" marginwidth="0" marginheight="0" scrolling="no" class="wp-embedded-content"></iframe><script> /*! This file is auto-generated */ !function(d,l){"use strict";l.querySelector&&d.addEventListener&&"undefined"!=typeof URL&&(d.wp=d.wp||{},d.wp.receiveEmbedMessage||(d.wp.receiveEmbedMessage=function(e){var t=e.data;if((t||t.secret||t.message||t.value)&&!/[^a-zA-Z0-9]/.test(t.secret)){for(var s,r,n,a=l.querySelectorAll('iframe[data-secret="'+t.secret+'"]'),o=l.querySelectorAll('blockquote[data-secret="'+t.secret+'"]'),c=new RegExp("^https?:$","i"),i=0;i<o.length;i++)o[i].style.display="none";for(i=0;i<a.length;i++)s=a[i],e.source===s.contentWindow&&(s.removeAttribute("style"),"height"===t.message?(1e3<(r=parseInt(t.value,10))?r=1e3:~~r<200&&(r=200),s.height=r):"link"===t.message&&(r=new URL(s.getAttribute("src")),n=new URL(t.value),c.test(n.protocol))&&n.host===r.host&&l.activeElement===s&&(d.top.location.href=t.value))}},d.addEventListener("message",d.wp.receiveEmbedMessage,!1),l.addEventListener("DOMContentLoaded",function(){for(var e,t,s=l.querySelectorAll("iframe.wp-embedded-content"),r=0;r<s.length;r++)(t=(e=s[r]).getAttribute("data-secret"))||(t=Math.random().toString(36).substring(2,12),e.src+="#?secret="+t,e.setAttribute("data-secret",t)),e.contentWindow.postMessage({message:"ready",secret:t},"*")},!1)))}(window,document); //# sourceURL=https://futurenews24.com/wp-includes/js/wp-embed.min.js </script> https://media.springernature.com/m685/springer-static/image/art%3A10.1038%2Fs41428-026-01212-2/MediaObjects/41428_2026_1212_Figa_HTML.png10241024The therapeutic use of proteins often depends on cytosolic access, which is frequently limited by endosomal trapping. Here, we developed pH-responsive amphiphilic peptide nanofibers (NFs) that may facilitate cytosolic protein delivery by selectively destabilizing endosomal membranes. We prepared a series of NFs by varying the number of glutamic acid residues (CE1, CE2, and CE3) appended to β-sheet-forming peptides. The resulting nanofibers were uniform in width and presented hydrophobic surface domains. Among these, CE2 NFs emerged as optimal: red blood cell hemolysis assays showed strong activity at mildly acidic pH, but they remained inert at neutral pH. In cells, a pH-sensitive FITC–PEG probe revealed a time-dependent increase in fluorescence with CE2 NFs, which is consistent with the translocation of the probe from acidic endosomes to the neutral cytosol, supporting endosomal-membrane destabilization by CE2 NFs. Furthermore, in OVA-treated dendritic cells, CE2 NFs increased surface SIINFEKL–H-2Kb presentation to levels comparable to the L17E peptide, a reagent known to promote cytosolic protein delivery. These results suggest that CE2 NFs facilitate the cytosolic translocation of coadministered proteins. In contrast, monomeric peptides showed no endosomal escape-promoting activity, supporting the necessity of self-assembled nanofiber architecture. Collectively, these findings suggest that pH-responsive peptide nanofibers serve as effective facilitators of cytosolic protein delivery via endosome-selective membrane destabilization. We developed pH-responsive amphiphilic peptide nanofibers (NFs) that may facilitate cytosolic protein delivery by selectively destabilizing endosomal membranes. The NFs were based on β-sheet-forming peptides conjugated with oligoglutamic acid segments, and the number of Glu residues was varied to optimize pH-responsive activity. Optimized NFs showed strong membrane-destabilizing activity at mildly acidic pH but remained inert at neutral pH. When coadministered with ovalbumin (OVA) to dendritic cells, these NFs increased major histocompatibility complex (MHC) class I presentation of the OVA-derived SIINFEKL epitope, supporting cytosolic delivery of OVA.