{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:54:53Z","timestamp":1792292093813,"version":"4.4.0"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Controlled Release"],"published-print":{"date-parts":[[2023,11]]},"DOI":"10.1016\/j.jconrel.2023.09.022","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T07:44:54Z","timestamp":1695714294000},"page":"101-113","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Control of cell penetration enhancer shielding and endosomal escape-kinetics crucial for efficient and biocompatible siRNA delivery"],"prefix":"10.1016","volume":"363","author":[{"given":"Alessio","family":"Malfanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider","family":"Sami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Balasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Marostica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busra","family":"Arpac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mastrotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mantovani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Cola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Anton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Caliceti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Ogris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Salmaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jconrel.2023.09.022_bb0005","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1089\/hum.2015.070","article-title":"Oligonucleotide therapies: the past and the present","volume":"26","author":"Lundin","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0010","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22073295","article-title":"Recent advances in oligonucleotide therapeutics in oncology","volume":"22","author":"Xiong","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0015","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1006304","article-title":"A perspective on oligonucleotide therapy: approaches to patient customization","volume":"13","author":"Thakur","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0020","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/978-3-642-31659-3_9","article-title":"Oligonucleotide therapeutics in cancer","volume":"158","author":"Wan","year":"2013","journal-title":"Cancer Treat. Res."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0025","doi-asserted-by":"crossref","first-page":"6518","DOI":"10.1093\/nar\/gkw236","article-title":"The delivery of therapeutic oligonucleotides","volume":"44","author":"Juliano","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0030","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ejpb.2018.04.018","article-title":"Non-viral based miR delivery and recent developments","volume":"128","author":"Labatut","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0035","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.omtm.2020.07.015","article-title":"Barriers and strategies of cationic liposomes for Cancer gene therapy","volume":"18","author":"Liu","year":"2020","journal-title":"Mol. Ther. Meth. Clin. Dev."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0040","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2016.06.023","article-title":"Progress in the development of lipopolyplexes as efficient non-viral gene delivery systems","volume":"236","author":"Rezaee","year":"2016","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0045","doi-asserted-by":"crossref","first-page":"13003","DOI":"10.1073\/pnas.97.24.13003","article-title":"The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters","volume":"97","author":"Wender","year":"2000","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0050","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1021\/ol051496y","article-title":"Dendrimeric molecular transporters: synthesis and evaluation of tunable polyguanidino dendrimers that facilitate cellular uptake","volume":"7","author":"Wender","year":"2005","journal-title":"Org. Lett."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0055","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1021\/mp9002464","article-title":"Dendrimer internalization and intracellular trafficking in living cells","volume":"7","author":"Albertazzi","year":"2010","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0060","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.3390\/molecules22111929","article-title":"Cell-penetrating peptides: design strategies beyond primary structure and amphipathicity","volume":"22","author":"Kalafatovic","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0065","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1038\/s41467-021-23997-x","article-title":"Unravelling cytosolic delivery of cell penetrating peptides with a quantitative endosomal escape assay","volume":"12","author":"Teo","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0070","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.3390\/ph5111177","article-title":"Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges","volume":"5","author":"Erazo-Oliveras","year":"2012","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0075","doi-asserted-by":"crossref","first-page":"295","DOI":"10.2217\/nnm.13.204","article-title":"Nanotoxicity: a key obstacle to clinical translation of siRNA-based nanomedicine","volume":"9","author":"Xue","year":"2014","journal-title":"Nanomedicine (London)"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0080","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.biomaterials.2015.11.056","article-title":"Effect of surface properties on liposomal siRNA delivery","volume":"79","author":"Xia","year":"2016","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0085","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines6020051","article-title":"Cell-penetrating peptides to enhance delivery of oligonucleotide-based therapeutics","volume":"6","author":"McClorey","year":"2018","journal-title":"Biomedicines"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0090","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1038\/s41467-020-15300-1","article-title":"Imaging small molecule-induced endosomal escape of siRNA","volume":"11","author":"Du Rietz","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0095","doi-asserted-by":"crossref","first-page":"120012","DOI":"10.1016\/j.ijpharm.2020.120012","article-title":"Doxorubicin liposomes cell penetration enhancement and its potential drawbacks for the tumor targeting efficiency","volume":"592","author":"Popilski","year":"2021","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0100","doi-asserted-by":"crossref","first-page":"17646","DOI":"10.1021\/acsami.8b03469","article-title":"pH-controlled liposomes for enhanced cell penetration in tumor environment","volume":"10","author":"Barattin","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0105","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0022-2836(65)80093-6","article-title":"Diffusion of univalent ions across the lamellae of swollen phospholipids","volume":"13","author":"Bangham","year":"1965","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0110","first-page":"13","article-title":"\u00dcber die katalytische wirkung des blutfarb-stoffes auf natriumhypochlorit nebst einer neuen farbenreaktion des blutes","volume":"5","author":"Sakaguchi","year":"1925","journal-title":"J. Biochem."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0115","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/0003-2697(80)90492-3","article-title":"A method for the estimation of polyethylene glycol in plasma protein fractions","volume":"107","author":"Sims","year":"1980","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0120","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0003-2697(80)90269-9","article-title":"Colorimetric determination of phospholipids with ammonium ferrothiocyanate","volume":"104","author":"Stewart","year":"1980","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0125","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/hgtb.2016.027","article-title":"Up-scaled synthesis and characterization of nonviral gene delivery particles for transient in vitro and in vivo transgene expression","volume":"27","author":"Taschauer","year":"2016","journal-title":"Human Gene Therapy Methods"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0130","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/mt.2012.229","article-title":"Systemic TNFalpha gene therapy synergizes with liposomal doxorubicine in the treatment of metastatic cancer","volume":"21","author":"Su","year":"2013","journal-title":"Mol. Ther."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0135","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/978-1-4939-9092-4_15","article-title":"Firefly Luciferase-Based Reporter Gene Assay for Investigating Nanoparticle-Mediated Nucleic Acid Delivery","volume":"1943","author":"M\u00fcller","year":"2019","journal-title":"Meth. ,Mol. Biol. (Clifton, N.J.)"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0140","doi-asserted-by":"crossref","first-page":"44826","DOI":"10.1074\/jbc.M308643200","article-title":"Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes","volume":"278","author":"Sonawane","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0145","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1038\/s41388-022-02241-w","article-title":"Targeted siRNA nanocarrier: a platform technology for cancer treatment","volume":"41","author":"B\u00e4umer","year":"2022","journal-title":"Oncogene"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0150","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1021\/bc025663f","article-title":"Synthesis of novel cationic lipids having Polyamidoamine Dendrons and their transfection activity","volume":"14","author":"Takahashi","year":"2003","journal-title":"Bioconjug. Chem."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0155","doi-asserted-by":"crossref","first-page":"11186","DOI":"10.1021\/acs.langmuir.5b01979","article-title":"Supramolecular organization and siRNA binding of hyaluronic acid-coated Lipoplexes for targeted delivery to the CD44 receptor","volume":"31","author":"Nascimento","year":"2015","journal-title":"Langmuir"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0160","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0301-4622(02)00339-3","article-title":"Thermodynamic analysis of binding and protonation in DOTAP\/DOPE (1:1): DNA complexes using isothermal titration calorimetry","volume":"104","author":"Lobo","year":"2003","journal-title":"Biophys. Chem."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0165","doi-asserted-by":"crossref","first-page":"11186","DOI":"10.1021\/acs.langmuir.5b01979","article-title":"Supramolecular organization and siRNA binding of hyaluronic acid-coated Lipoplexes for targeted delivery to the CD44 receptor","volume":"31","author":"Nascimento","year":"2015","journal-title":"Langmuir"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0170","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1016\/S0006-3495(03)74811-5","article-title":"Lipoplex thermodynamics: determination of DNA-cationic lipoid interaction energies","volume":"85","author":"Pozharski","year":"2003","journal-title":"Biophys. J."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0175","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1161\/01.CIR.23.4.578","article-title":"Plasma heparin levels in normal man","volume":"23","author":"Engelberg","year":"1961","journal-title":"Circulation"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0180","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1016\/j.nano.2017.04.009","article-title":"Effect of size and pegylation of liposomes and peptide-based synthetic lipoproteins on tumor targeting","volume":"13","author":"Tang","year":"2017","journal-title":"Nanomedicine"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0185","doi-asserted-by":"crossref","first-page":"4996","DOI":"10.1016\/j.biomaterials.2014.03.007","article-title":"Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging","volume":"35","author":"Majzoub","year":"2014","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0190","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1016\/j.ymthe.2019.07.018","article-title":"Endocytic profiling of cancer cell models reveals critical factors influencing LNP-mediated mRNA delivery and protein expression","volume":"27","author":"Sayers","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0195","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-017-0271-8","article-title":"A mechanistic investigation exploring the differential transfection efficiencies between the easy-to-transfect SK-BR3 and difficult-to-transfect CT26 cell lines","volume":"15","author":"Figueroa","year":"2017","journal-title":"J. Nanobiotechnol."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0200","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3390\/cells10061519","article-title":"Mapping surface charge distribution of single-cell via charged nanoparticle","volume":"10","author":"Ouyang","year":"2021","journal-title":"Cells"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0205","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1111\/febs.16247","article-title":"The antimetastatic breast cancer activity of the viral protein-derived peptide vCPP2319 as revealed by cellular biomechanics","volume":"289","author":"Oliveira","year":"2022","journal-title":"FEBS J."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0210","doi-asserted-by":"crossref","first-page":"6298","DOI":"10.1038\/s41598-019-42456-8","article-title":"Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines","volume":"9","author":"Patel","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0215","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/sj.gt.3300745","article-title":"The size of DNA\/transferrin-PEI complexes is an important factor for gene expression in cultured cells","volume":"5","author":"Ogris","year":"1998","journal-title":"Gene Ther."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0220","doi-asserted-by":"crossref","first-page":"13738","DOI":"10.1038\/s41598-017-14221-2","article-title":"A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery","volume":"7","author":"Wolfram","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0225","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1039\/D0CS01127D","article-title":"Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine","volume":"50","author":"Sousa de Almeida","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0230","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jconrel.2008.06.001","article-title":"Dynamics of photoinduced endosomal release of polyplexes","volume":"130","author":"de Bruin","year":"2008","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0235","doi-asserted-by":"crossref","first-page":"30095","DOI":"10.1021\/acsami.0c06608","article-title":"Combined chemisorption and complexation generate siRNA Nanocarriers with biophysics optimized for efficient gene knockdown and air-blood barrier crossing","volume":"12","author":"Taschauer","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"10.1016\/j.jconrel.2023.09.022_bb0240","doi-asserted-by":"crossref","first-page":"8090","DOI":"10.1093\/nar\/gky703","article-title":"Structural basis for the synergy of 4\u2032- and 2\u2032-modifications on siRNA nuclease resistance, thermal stability and RNAi activity","volume":"46","author":"Harp","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0245","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1016\/j.ymthe.2019.07.018","article-title":"Endocytic profiling of Cancer cell models reveals critical factors influencing LNP-mediated mRNA delivery and protein expression","volume":"27","author":"Sayers","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.jconrel.2023.09.022_bb0250","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abn2941","article-title":"Copackaging photosensitizer and PD-L1 siRNA in a nucleic acid nanogel for synergistic cancer photoimmunotherapy","volume":"8","author":"Guo","year":"2022","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jconrel.2023.09.022_bib253","doi-asserted-by":"crossref","first-page":"5148","DOI":"10.1021\/acs.biomac.2c00993","article-title":"Mannosylated polycations target CD206+- antigen presenting cells and mediate T-cell specific activation in cancer vaccination","volume":"23","author":"Bellato","year":"2022","journal-title":"Biomacromolecules"}],"container-title":["Journal of Controlled Release"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365923006107?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365923006107?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T16:46:21Z","timestamp":1759164381000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168365923006107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11]]},"references-count":51,"alternative-id":["S0168365923006107"],"URL":"https:\/\/doi.org\/10.1016\/j.jconrel.2023.09.022","relation":{},"ISSN":["0168-3659"],"issn-type":[{"value":"0168-3659","type":"print"}],"subject":[],"published":{"date-parts":[[2023,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Control of cell penetration enhancer shielding and endosomal escape-kinetics crucial for efficient and biocompatible siRNA delivery","name":"articletitle","label":"Article Title"},{"value":"Journal of Controlled Release","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jconrel.2023.09.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}