title: Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: A synergistic combination nanotherapy for ovarian cancer treatment.
abstract: Cisplatin (CDDP) and paclitaxel (PTX) are two established chemotherapeutic drugs used in combination for the treatment of many cancers, including ovarian cancer. We have recently developed a three-layered linear-dendritic telodendrimer micelles (TM) by introducing carboxylic acid groups in the adjacent layer via "thio-ene" click chemistry for CDDP complexation and conjugating cholic acids via peptide chemistry in the interior layer of telodendrimer for PTX encapsulation. We hypothesize that the co-delivery of low dosage PTX with CDDP could act synergistically to increase the treatment efficacy and reduce their toxic side effects. This design allowed us to co-deliver PTX and CDDP at various drug ratios to ovarian cancer cells. The in vitro cellular assays revealed strongest synergism in anti-tumor effects when delivered at a 1:2 PTX/CDDP loading ratio. Using the SKOV-3 ovarian cancer xenograft mouse model, we demonstrate that our co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and stronger anti-tumor effect, when compared with free drug combination or the single loading TM formulations.
authors.affiliation: Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.|Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei 430022, China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.|Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
authors.forename: Gaofei
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Changying
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Dandan
authors.initials: D
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
authors.forename: Juntao
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008027:Light; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000494:pharmacology; D010316:Particle Size; D066244:Proton Magnetic Resonance Spectroscopy; D012542:Scattering, Radiation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D017239:Paclitaxel; D002945:Cisplatin
keywords: Cisplatin; Combination chemotherapy; Drug delivery; Ovarian cancer; Paclitaxel; Synergism