title: Supramolecular "Trojan Horse" for Nuclear Delivery of Dual Anticancer Drugs.
abstract: Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Haosheng
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Liuhan
authors.initials: L
authors.lastname: Dai
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College , Tianjin 300192, P. R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College , Tianjin 300192, P. R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Jie
authors.identifier: 0000-0002-6186-2750
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University , Tianjin 300071, P. R. China.
authors.forename: Zhimou
authors.identifier: 0000-0003-2967-6920
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D050997:Nanomedicine; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D046911:Macromolecular Substances; C028098:10-hydroxycamptothecin; D002945:Cisplatin; D002166:Camptothecin