title: Construction of a two-in-one liposomal system (TWOLips) for tumor-targeted combination therapy.
abstract: In oncology, there is a growing need for simpler, more selective methods to deliver drug therapies directly to the tumor site. For combination therapies, simultaneous targeted delivery of multiple drugs would represent a significant improvement. In contrast to previous work that took a de novo approach, we constructed a novel two-in-one liposomal system (TWOLips) from two single drug-loaded liposomes. Our results demonstrated that TWOLips could be prepared by a simple process, through silica coating of one liposome and incubation with the second liposome. TWOLips had a mean diameter of 100 nm, relatively high drug loading rates (96.8%±0.9% for doxorubicin and 78.4%±1.2% for combretastatin), and high storage stability. TWOLips modification by adding a targeting moiety, an all D-amino acid peptide derived from a natural vascular endothelial growth factor, resulted in strong, selective binding to vascular endothelial growth factor receptor 2, a tumorigenesis marker, in vitro and in vivo. TWOLips significantly inhibited tumor growth and angiogenesis and enhanced survival in mice with A375 melanoma xenografts. The TWOLips system had a low potential risk of toxicity. Since the stepwise assembly could be carried further (additional drug-loaded liposomes), TWOLips shows potential as a treatment for many cancers, especially those that require multiple drugs.
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Su
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Long
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China.
authors.forename: Chunyue
authors.initials: C
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Fudan University, Shanghai 201203, China.
authors.forename: Linglin
authors.initials: L
authors.lastname: Feng
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China. Electronic address: xiczb86@126.com.
authors.forename: Zhangbao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Luminescence and Real-time Analytical Chemistry, Ministry of Education, Southwest University, Chongqing 400715, China; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, Fudan University, Shanghai 201203, China. Electronic address: chongli2009@gmail.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D001632:Bibenzyls / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001632:Bibenzyls; D004338:Drug Combinations; D008081:Liposomes; D012822:Silicon Dioxide; C040105:combretastatin; D004317:Doxorubicin
keywords: Combination therapy; Combretastatin A4; Doxorubicin; VEGFR2; d-peptide