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dc.contributor.authorChen, Charles H
dc.contributor.authorLiu, Yu-Han
dc.contributor.authorEskandari, Arvin
dc.contributor.authorGhimire, Jenisha
dc.contributor.authorLin, Leon Chien-Wei
dc.contributor.authorFang, Zih-Syun
dc.contributor.authorWimley, William C
dc.contributor.authorUlmschneider, Jakob P
dc.contributor.authorSuntharalingam, Kogularamanan
dc.contributor.authorHu, Che-Ming Jack
dc.contributor.authorUlmschneider, Martin B
dc.date.accessioned2022-03-05T09:00:18Z
dc.date.available2022-03-05T09:00:18Z
dc.date.issued2022-05
dc.date.submitted2021-11-29
dc.identifier.issn2198-3844
dc.identifier.otheradvs3581
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334694
dc.descriptionFunder: KCL PhD scholarships
dc.descriptionFunder: Leverhulme Trust; Id: http://dx.doi.org/10.13039/501100000275
dc.description.abstractMembrane-lytic peptides offer broad synthetic flexibilities and design potential to the arsenal of anticancer therapeutics, which can be limited by cytotoxicity to noncancerous cells and induction of drug resistance via stress-induced mutagenesis. Despite continued research efforts on membrane-perforating peptides for antimicrobial applications, success in anticancer peptide therapeutics remains elusive given the muted distinction between cancerous and normal cell membranes and the challenge of peptide degradation and neutralization upon intravenous delivery. Using triple-negative breast cancer as a model, the authors report the development of a new class of anticancer peptides. Through function-conserving mutations, the authors achieved cancer cell selective membrane perforation, with leads exhibiting a 200-fold selectivity over non-cancerogenic cells and superior cytotoxicity over doxorubicin against breast cancer tumorspheres. Upon continuous exposure to the anticancer peptides at growth-arresting concentrations, cancer cells do not exhibit resistance phenotype, frequently observed under chemotherapeutic treatment. The authors further demonstrate efficient encapsulation of the anticancer peptides in 20 nm polymeric nanocarriers, which possess high tolerability and lead to effective tumor growth inhibition in a mouse model of MDA-MB-231 triple-negative breast cancer. This work demonstrates a multidisciplinary approach for enabling translationally relevant membrane-lytic peptides in oncology, opening up a vast chemical repertoire to the arms race against cancer.
dc.languageen
dc.publisherWiley
dc.subjectResearch Article
dc.subjectResearch Articles
dc.subjectanticancer peptides
dc.subjectdrug resistance
dc.subjectmembrane‐active anticancer agents
dc.subjectmulticellular tumor spheroids
dc.subjectmurine models
dc.subjectnanoparticles
dc.subjecttriple negative breast cancer
dc.titleIntegrated Design of a Membrane-Lytic Peptide-Based Intravenous Nanotherapeutic Suppresses Triple-Negative Breast Cancer.
dc.typeArticle
dc.date.updated2022-03-05T09:00:17Z
prism.publicationNameAdv Sci (Weinh)
dc.identifier.doi10.17863/CAM.82112
rioxxterms.versionofrecord10.1002/advs.202105506
rioxxterms.versionAO
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidUlmschneider, Martin B [0000-0001-8103-0516]
dc.identifier.eissn2198-3844
pubs.funder-project-idChina 1000 Plan's Program for Young Talents (13Z127060001)
cam.issuedOnline2022-03-04


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