{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:35:44Z","timestamp":1773264944030,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T00:00:00Z","timestamp":1576108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/QUI\/50006\/2019"],"award-info":[{"award-number":["UID\/QUI\/50006\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PD\/BD\/106035\/2015"],"award-info":[{"award-number":["PD\/BD\/106035\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-094579-B-I00"],"award-info":[{"award-number":["RTI2018-094579-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates.<\/jats:p>","DOI":"10.3390\/molecules24244559","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T11:06:41Z","timestamp":1576148801000},"page":"4559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates"],"prefix":"10.3390","volume":"24","author":[{"given":"Lu\u00edsa","family":"Aguiar","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-8991","authenticated-orcid":false,"given":"Arnau","family":"Biosca","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"}]},{"given":"Elena","family":"Lantero","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"}]},{"given":"Jiri","family":"Gut","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California at San Francisco, 1001 Potrero Avenue, San Francisco, San Francisco, CA 94110, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia da Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"IPATIMUP\u2014Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7953-7622","authenticated-orcid":false,"given":"Philip J.","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"School of Medicine, University of California at San Francisco, 1001 Potrero Avenue, San Francisco, San Francisco, CA 94110, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-0778","authenticated-orcid":false,"given":"F\u00e1tima","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349-008 Lisbon, Portugal"}]},{"given":"David","family":"Andreu","sequence":"additional","affiliation":[{"name":"Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-9631","authenticated-orcid":false,"given":"Xavier","family":"Fern\u00e0ndez-Busquets","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"},{"name":"Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Mart\u00ed i Franqu\u00e8s 1, 08028 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-4724","authenticated-orcid":false,"given":"Paula","family":"Gomes","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nrmicro1529","article-title":"The silent path to thousands of merozoites: The Plasmodium liver stage","volume":"4","author":"Mota","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1002\/cmdc.201500164","article-title":"N-Cinnamoylation of antimalarial classics: Effects of using acyl groups other than cinnamoyl toward dual-stage antimalarials","volume":"10","author":"Gomes","year":"2015","journal-title":"ChemMedChem"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1021\/jm0494624","article-title":"Imidazolidin-4-one derivatives of primaquine as novel transmission-blocking antimalarials","volume":"48","author":"Bom","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7800","DOI":"10.1021\/jm900738c","article-title":"Imidazoquines as antimalarial and anti-pneumocystis agents","volume":"52","author":"Vale","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1128\/AAC.05345-11","article-title":"Novel potent metallocenes against liver stage malaria","volume":"56","author":"Matos","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1039\/c2md20113e","article-title":"PRIMACINS, N-Cinnamoyl-Primaquine conjugates, with improved liver-stage antimalarial activity","volume":"3","author":"Perez","year":"2012","journal-title":"MedChemComm"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1021\/jm301654b","article-title":"N-Cinnamoylated chloroquine analogues as dual-stage antimalarial leads","volume":"56","author":"Teixeira","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/cmdc.201300459","article-title":"N-Cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity","volume":"9","author":"Gomes","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"56134","DOI":"10.1039\/C6RA10759A","article-title":"Primaquine-based ionic liquids as a novel class of antimalarial hits","volume":"6","author":"Ferraz","year":"2016","journal-title":"RSC Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.biomaterials.2017.08.020","article-title":"ImmunoPEGliposomes for the targeted delivery of novel lipophilic drugs to red blood cells in a falciparum malaria murine model","volume":"145","author":"Moles","year":"2017","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/j.febslet.2013.04.031","article-title":"Cell-Penetrating peptides: 20 years later, where do we stand?","volume":"587","author":"Bechara","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.tips.2012.02.002","article-title":"Peptides for cell-selective drug delivery","volume":"33","author":"Svensen","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jconrel.2017.02.006","article-title":"Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides","volume":"250","author":"Dissanayake","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, Y., Cheetham, A.G., Angacian, G., Su, H., Xie, L., and Cui, H. (2017). Peptide\u2013drug conjugates as effective prodrug strategies for targeted delivery. Adv. Drug Deliv. Rev., 112\u2013126.","DOI":"10.1016\/j.addr.2016.06.015"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbcan.2011.07.006","article-title":"Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer","volume":"1816","author":"Bolhassani","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)-Rev.  Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4689","DOI":"10.1128\/AAC.00427-13","article-title":"Improved efficacy of fosmidomycin against Plasmodium and Mycobacterium species by combination with the cell-penetrating peptide octaarginine","volume":"57","author":"Sparr","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1128\/AAC.01450-07","article-title":"Cell-penetrating peptide TP10 shows broad-spectrum activity against both Plasmodium falciparum and Trypanosoma brucei brucei","volume":"52","author":"Arrighi","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1124\/mol.105.019364","article-title":"Use of penetrating peptides interacting with PP1\/PP2A proteins as a general approach for a drug phosphatase technology","volume":"69","author":"Guergnon","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/psc.2708","article-title":"Peptide IDR-1018: Modulating the immune system and targeting bacterial biofilms to treat antibiotic-resistant bacterial infections","volume":"21","author":"Mansour","year":"2015","journal-title":"J. Pept. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1039\/C8MD00447A","article-title":"Coupling the cell-penetrating peptides transportan and transportan 10 to primaquine enhances its activity against liver-stage malaria parasites","volume":"10","author":"Aguiar","year":"2019","journal-title":"MedChemComm"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1086\/322858","article-title":"Chloroquine-Resistant malaria","volume":"184","author":"Wellems","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"661","DOI":"10.4269\/ajtmh.2002.66.661","article-title":"In vitro reversal of chloroquine resistance in Plasmodium falciparum with dihydroethanoanthracene derivatives","volume":"66","author":"Pradines","year":"2002","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/bip.22785","article-title":"Effect of spacer length and type on the biological activity of peptide-polysaccharide matrices","volume":"106","author":"Kumai","year":"2016","journal-title":"Pept. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2174\/1567201813666160224123450","article-title":"Spacer Length: A Determining Factor in the Design of Galactosyl Ligands for Hepatoma Cell-Specific Liposomal Gene Delivery","volume":"13","author":"Mbatha","year":"2016","journal-title":"Curr. Drug Deliv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.ejmech.2018.01.017","article-title":"In vitro antiplasmodial efficacy of synthetic coumarin-triazole analogs","volume":"145","author":"Yadav","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/cbdd.12321","article-title":"New compounds hybrids 1H-1,2,3-triazole-quinoline against Plasmodium falciparum","volume":"84","author":"Boechat","year":"2014","journal-title":"Chem. Boil. Drug Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4561","DOI":"10.1016\/j.bmcl.2011.05.119","article-title":"Antiplasmodial and cytotoxicity evaluation of 3-functionalized 2-azetidinone derivatives","volume":"21","author":"Singh","year":"2011","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1021\/jm901178d","article-title":"Synthesis and Antiprotozoal activity of cationic 1,4-diphenyl-1H-1,2,3-triazoles","volume":"53","author":"Bakunov","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9389","DOI":"10.1073\/pnas.94.17.9389","article-title":"Variations in frequencies of drug resistance in Plasmodium falciparum","volume":"94","author":"Rathod","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.pt.2012.08.002","article-title":"PfCRT and its role in antimalarial drug resistance","volume":"28","author":"Ecker","year":"2012","journal-title":"Trends Parasitol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chinappi, M., Via, A., Marcatili, P., and Tramontano, A. (2010). On the mechanism of chloroquine resistance in Plasmodium falciparum. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014064"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/med.10016","article-title":"Chloroquine resistance in the malarial parasite, Plasmodium falciparum","volume":"22","author":"Ursos","year":"2002","journal-title":"Med. Res. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"14552","DOI":"10.1038\/srep14552","article-title":"Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite\u2019s food vacuole and alter drug sensitivities","volume":"5","author":"Pulcini","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1128\/AAC.02476-15","article-title":"Overcoming chloroquine resistance in malaria: Design, synthesis, and structure-activity relationships of novel hybrid compounds","volume":"60","author":"Boudhar","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1002\/anie.201510518","article-title":"An intrinsically disordered peptide facilitates non-endosomal cell entry","volume":"55","author":"Medina","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1128\/AAC.00624-13","article-title":"Identification of cell-penetrating peptides that are bactericidal to Neisseria meningitidis and prevent inflammatory responses upon infection","volume":"57","author":"Eriksson","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/BF00931147","article-title":"Microscopic and flow cytophotometric analysis of parasitemia in cultures of Plasmodium falciparum vitally stained with Hoechst 33342\u2014application to studies of antimalarial agents","volume":"72","author":"Franklin","year":"1986","journal-title":"Zeitschrift f\u00fcr Parasitenkunde"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/anie.201508445","article-title":"MiniAp-4: A venom-inspired peptidomimetic for brain delivery","volume":"55","author":"Ciudad","year":"2016","journal-title":"Angew. Chemie Int. Ed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1073\/pnas.1619441114","article-title":"Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse in Plasmodium falciparum egress","volume":"114","author":"Hale","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1182\/blood-2014-12-512772","article-title":"Anatomy of the red cell membrane skeleton: Unanswered questions","volume":"127","author":"Lux","year":"2016","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"065303","DOI":"10.1063\/1.4985052","article-title":"Erythrocyte membrane skeleton inhibits nanoparticle endocytosis","volume":"7","author":"Gao","year":"2017","journal-title":"AIP Adv."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Minetti, G., Achilli, C., Perotti, C., and Ciana, A. (2018). continuous change in membrane and membrane-skeleton organization during development from proerythroblast to senescent red blood cell. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00286"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1083\/jcb.141.3.791","article-title":"Regulation of endothelial cell motility by complexes of tetraspan molecules CD81\/TAPA-1 and CD151\/PETA-3 with alpha 3beta 1 integrin localized at endothelial lateral junctions","volume":"141","author":"Alfranca","year":"1998","journal-title":"J. Cell Boil."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/j.1365-2141.2011.08766.x","article-title":"Cytoskeletal and membrane remodelling during malaria parasite invasion of the human erythrocyte","volume":"154","author":"Zuccala","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1016\/j.bpj.2012.11.008","article-title":"Red blood cell membrane dynamics during malaria parasite egress","volume":"103","author":"Arriagada","year":"2012","journal-title":"Biophys. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.actatropica.2010.01.013","article-title":"Early transcriptional response to chloroquine of the Plasmodium falciparum antioxidant defence in sensitive and resistant clones","volume":"114","author":"Nogueira","year":"2010","journal-title":"Acta Trop."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/psc.804","article-title":"Limiting racemization and aspartimide formation in microwave-enhanced Fmoc solid phase peptide synthesis","volume":"13","author":"Palasek","year":"2007","journal-title":"J. Pept. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1021\/ol702228u","article-title":"Click chemistry as a macrocyclization tool in the solid-phase synthesis of small cyclic peptides","volume":"9","author":"Turner","year":"2007","journal-title":"Org. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s10989-017-9642-0","article-title":"A tetra-orthogonal strategy for the efficient synthesis of scaffolds based on cyclic peptides","volume":"24","author":"Jain","year":"2018","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1034\/j.1399-3011.2002.21018.x","article-title":"The kinetics of the removal of the N-methyltrityl (Mtt) group during the synthesis of branched peptides","volume":"60","author":"Li","year":"2002","journal-title":"J. Pept. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.biopha.2018.09.097","article-title":"Cell penetrating peptides: A concise review with emphasis on biomedical applications","volume":"108","author":"Derakhshankhah","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.tips.2017.01.003","article-title":"Cell-penetrating peptides: From basic research to clinics","volume":"38","author":"Guidotti","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_53","first-page":"S267","article-title":"Cell-Penetrating peptides: A useful tool for the delivery of various cargoes into cells","volume":"67","author":"Pechar","year":"2018","journal-title":"Physiol. Res."},{"key":"ref_54","first-page":"211","article-title":"Cell penetrating peptides: A promising tool for the cellular uptake of macromolecular drugs","volume":"19","author":"Zhu","year":"2018","journal-title":"Protein Pept. Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4559\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:41:56Z","timestamp":1760190116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,12]]},"references-count":54,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24244559"],"URL":"https:\/\/doi.org\/10.3390\/molecules24244559","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,12]]}}}