title: Redox-Sensitive Citronellol-Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine.
abstract: Citronellol-cabazitaxel (CIT-ss-CTX) conjugate self-assembled nanoparticles (CSNPs) were designed and prepared by conjugating cabazitaxel with citronellol via the disulfide bond that is redox-sensitive to the high concentration of glutathione within tumor cells. Notably, the CSNPs maintained in the cell cytotoxicity. Moreover, the AUC0-t of CSNPs was 6.5-fold higher than that of cabazitaxel solutions and the t1/2 was prolonged 2.3 times. Furthermore, we found that CSNPs could be employed as an efficient carrier for other hydrophobic drugs or imaging agents. Thus, the in vivo targeting study was implemented via using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-loaded CSNPs as imaging agent, which showed CSNPs could effectively accumulate at the tumor site. Curcumin, a hydrophobic anticancer drug, was successfully loaded in CSNPs which exhibits good stability and synergistic antitumor effects. The citronellol-cabazitaxel conjugate therefore has a promising perspective as a multifunctional nanomedicine for combination therapy and theranostics attributed to its long-circulation property, redox-sensitive mechanism, and high drug coloading capability.
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Guo
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Mengchi
authors.initials: M
authors.lastname: Sun
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Pharmacy and ‡Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University , No. 103, Wenhua Road, Shenyang, 110016, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001692:Biological Transport; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D004355:Drug Stability; D006801:Humans; D039821:Monoterpenes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction; D051381:Rats; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents; D004337:Drug Carriers; D039821:Monoterpenes; D043823:Taxoids; C552428:cabazitaxel; C007078:citronellol