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Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy
Zhou, Lingyun1,2; Lv, Fengting1,2; Liu, Libing1,2; Shen, Guizhi3; Yan, Xuehai3; Bazan, Guillermo C.4,5; Wang, Shu1,2
2018-03-08
Source PublicationADVANCED MATERIALS
ISSN0935-9648
Volume30Issue:10
AbstractHow to reduce the resistance of certain tumor cells to paclitaxel (PTX) and related taxoid anticancer drugs is a major challenge for improving cure rates. An oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX), which enhances drug efficacy and reverses resistance is thus designed. The mechanism involves diffusion of OPV-S-PTX into the cell, where pi-pi interactions lead to aggregation. Cross-linking of the aggregates via oxidation of thiol groups is favored in tumor cells because of the higher reactive oxygen species (ROS) concentration. Cross-linked aggregates "chemically lock" the multichromophore particle for a more persistent effect. The IC50 of OPV-S-PTX for tumor cell line A549 is reduced down to 0.33 x 10(-9) M from that observed for PTX itself (41 x 10(-9) M). Enhanced efficacy by OPV-S-PTX is proposed to proceed via acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice experiments reveal suppression of tumor growth upon OPV-S-PTX treatment. Altogether, these results show that the internal cross-linking of OPV-S-PTX through ROS provides a means to discriminate between tumor and healthy cells and the formation of the chemically locked particles enhances drug efficacy and helps in reducing resistance.
KeywordAntitumor Assembly Inside Cells Chemical Locks Drug Resistance Supramolecular Paclitaxel
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences ; Technology
DOI10.1002/adma.201704888
Indexed BySCI
Language英语
WOS KeywordMEDIATED MULTIDRUG-RESISTANCE ; OVARIAN-CANCER CELLS ; CELLULAR UPTAKE ; BREAST-CANCER ; TAXOL ; TRANSPORTERS ; THERAPY ; CIRCUMVENTION ; NANOPARTICLES ; MICROTUBULES
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS SubjectChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDA09030306) ; National Natural Science Foundation of China(21373243 ; 91527306 ; 21533012)
WOS IDWOS:000426720400007
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/24072
Collection生化工程国家重点实验室
Affiliation1.Chinese Acad Sci, Beijing Natl Lab Mol Sci, Key Lab Organ Solids, Inst Chem, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China
4.Univ Calif Santa Barbara, Dept Chem & Biochem, Ctr Polymers & Organ Solids, Santa Barbara, CA 93106 USA
5.Univ Calif Santa Barbara, Dept Mat, Ctr Polymers & Organ Solids, Santa Barbara, CA 93106 USA
Recommended Citation
GB/T 7714
Zhou, Lingyun,Lv, Fengting,Liu, Libing,et al. Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy[J]. ADVANCED MATERIALS,2018,30(10).
APA Zhou, Lingyun.,Lv, Fengting.,Liu, Libing.,Shen, Guizhi.,Yan, Xuehai.,...&Wang, Shu.(2018).Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy.ADVANCED MATERIALS,30(10).
MLA Zhou, Lingyun,et al."Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug Efficacy".ADVANCED MATERIALS 30.10(2018).
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