{"doi":"10.1002/pep2.24168","title":"How to overcome endosomal entrapment of cell‐penetrating peptides to release the therapeutic potential of peptides?","abstract":"<jats:title>Abstract</jats:title><jats:p>Peptides gained a renascent interest as alternative pharmaceuticals, and in particular as anticancer drugs to inhibit intracellular proteins involved in cancer pathways, inaccessible to other pharmaceutical agents. However, the use of peptides as therapeutics is still limited by difficulties in reaching the protein target located in the cytosol. Cell penetrating peptides (CPPs) are being explored as tools to deliver therapeutic peptides inside cells, but they often enter cells using endocytic pathways and become entrapped inside endosomes. Therefore, a strategy to unleash the potential of peptides as therapeutics is to control the release of CPPs from endosomes. In this review we summarize recent strategies employed to improve endosomal escape of CPPs. Lessons learned from these studies can guide the design of CPPs as tools to deliver peptide sequences able to inhibit cancer targets and accelerate their development as therapeutics.</jats:p>","journal":"Peptide Science","year":2020,"id":28605,"datarank":1.0216808292171944,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.5018204437972353,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.5018204437972353,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":25,"citers_with_citation_signal":22,"citers_with_endowment":22,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":159776,"name":"Sónia Troeira Henriques","orcid":"0000-0001-9564-9651","position":1,"is_corresponding":false},{"id":159775,"name":"Ferran Nadal‐Bufí","orcid":"0000-0002-1156-3410","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24523987","pmcid":null,"openalex_id":"https://openalex.org/W3021223209","authors":[],"funders":[{"funder_name":"Australian Research Council","grant_id":"FT150100398","title":"ARC Future Fellowships - Grant ID: FT150100398"},{"funder_name":"Queensland University of Technology","grant_id":"Postgraduate Research Award","title":null}],"total_grants":2,"fwci":1.417,"citation_percentile":0.81082369,"influential_citations":0,"citation_trend":[{"year":2021,"count":9},{"year":2022,"count":6},{"year":2023,"count":2},{"year":2024,"count":9},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"closed","license":"Wiley Online Library User Agreement","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fpep2.24168","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/pep2.24168","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pep2.24168","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/am-pdf/10.1002/pep2.24168","host_type":"publisher"},{"url":"https://doi.org/10.1002/pep2.24168","host_type":"journal"},{"url":"https://rss.onlinelibrary.wiley.com/doi/am-pdf/10.1002/pep2.24168","host_type":""},{"url":"https://espace.library.uq.edu.au/view/UQ:154bd7d","host_type":""},{"url":"https://api.library.uq.edu.au/view/UQ:154bd7d","host_type":""},{"url":"https://dx.doi.org/10.1002/pep2.24168","host_type":""},{"url":"https://doi.org/https://doi.org/10.1002/pep2.24168","host_type":""}],"fields_of_study":["RNA Interference and Gene Delivery","Advanced biosensing and bioanalysis techniques","Antimicrobial Peptides and Activities","Chemistry","Medicine","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":[],"keywords":["Endosome","Endocytic cycle","Cytosol","Cell-penetrating peptide","Intracellular","Peptide","Chemistry","Endocytosis","Cell biology","Cancer cell","Cell","Computational biology","Biochemistry","Biology","Cancer","Enzyme","1303 Biochemistry","intracellular delivery","Amphipathic Peptide","610","cell penetrating peptides","drug deliver","Membrane Interactions","Fusogenic Peptide","2502 Biomaterials","cellular uptake","Fusion Proteins","Lipid-Bilayers","peptide‐membrane interactions","540","Escape","Protein-Protein Interactions","In-Vitro","Delivery","Antimicrobial Peptides","1304 Biophysics","1605 Organic Chemistry"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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