title: Codelivery of chemotherapeutics via crosslinked multilamellar liposomal vesicles to overcome multidrug resistance in tumor.
abstract: Multidrug resistance (MDR) is a significant challenge to effective cancer chemotherapy treatment. However, the development of a drug delivery system that allows for the sustained release of combined drugs with improved vesicle stability could overcome MDR in cancer cells. To achieve this, we have demonstrated codelivery of doxorubicin (Dox) and paclitaxel (PTX) via a crosslinked multilamellar vesicle (cMLV). This combinatorial delivery system achieves enhanced drug accumulation and retention, in turn resulting in improved cytotoxicity against tumor cells, including drug-resistant cells. Moreover, this delivery approach significantly overcomes MDR by reducing the expression of P-glycoprotein (P-gp) in cancer cells, thus improving antitumor activity in vivo. Thus, by enhancing drug delivery to tumors and lowering the apoptotic threshold of individual drugs, this combinatorial delivery system represents a potentially promising multimodal therapeutic strategy to overcome MDR in cancer therapy.
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Jinxu
authors.initials: J
authors.lastname: Fang
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Kye-Il
authors.initials: KI
authors.lastname: Joo
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, United States of America; Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States of America; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D008081:Liposomes; D004317:Doxorubicin; D017239:Paclitaxel