{"data":{"id":"10.6084/m9.figshare.c.2110403.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2110403.v1","prefix":"10.6084","suffix":"m9.figshare.c.2110403.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Tang, Jie","givenName":"Jie","familyName":"Tang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Li","givenName":"Li","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Gao, Huile","givenName":"Huile","familyName":"Gao","affiliation":[],"nameIdentifiers":[]},{"name":"Liu, Yayuan","givenName":"Yayuan","familyName":"Liu","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Qianyu","givenName":"Qianyu","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Ran, Rui","givenName":"Rui","familyName":"Ran","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Zhirong","givenName":"Zhirong","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"He, Qin","givenName":"Qin","familyName":"He","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Co-delivery of doxorubicin and P-gp inhibitor by a reduction-sensitive liposome to overcome multidrug resistance, enhance anti-tumor efficiency and reduce toxicity"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biochemistry"},{"subject":"Space Science"},{"subject":"Cell Biology"},{"subject":"Pharmacology"},{"subject":"Biotechnology"},{"subject":"Chemical Sciences not elsewhere classified"},{"subject":"Cancer"},{"subject":"Infectious Diseases"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.c.2110403","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"To overcome multidrug resistance (MDR) in cancer chemotherapy with high efficiency and safety, a reduction-sensitive liposome (CL-R8-LP), which was co-modified with reduction-sensitive cleavable PEG and octaarginine (R8) to increase the tumor accumulation, cellular uptake and lysosome escape, was applied to co-encapsulate doxorubicin (DOX) and a P-glycoprotein (P-gp) inhibitor of verapamil (VER) in this study. The encapsulation efficiency (EE) of DOX and VER in the binary-drug loaded CL-R8-LP (DOX + VER) was about 95 and 70% (w/w), respectively. The uptake efficiencies, the cytotoxicity, and the apoptosis and necrosis-inducing efficiency of CL-R8-LP (DOX + VER) were much higher than those of DOX and the other control liposomes in MCF-7/ADR cells or tumor spheroids. Besides, CL-R8-LP (DOX + VER) was proven to be uptaken into MCF-7/ADR cells by clathrin-mediated and macropinocytosis-mediated endocytosis, followed by efficient lysosomal escape. \u003ci\u003eIn vivo\u003c/i\u003e, CL-R8-LP (DOX + VER) effectively inhibited the growth of MCF-7/ADR tumor and reduce the toxicity of DOX and VER, which could be ascribed to increased accumulation of drugs in drug-resistant tumor cells and reduced distribution in normal tissues. In summary, the co-delivery of chemotherapeutics and P-gp inhibitors by our reduction-sensitive liposome was a promising approach to overcome MDR, improve anti-tumor effect and reduce the toxicity of chemotherapy.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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