title: Human epidermal growth factor receptor-2 antibodies enhance the specificity and anticancer activity of light-sensitive doxorubicin-labeled liposomes.
abstract: Antibody-mediated targeting therapy has been successful in treating patients with cancers by improving the specificity and clinical efficacy. In this study, we developed a human epidermal growth factor receptor-2 (HER2) antibody-conjugated drug delivery system, using near-infrared (NIR) light-sensitive liposomes containing doxorubicin (DOX) and hollow gold nanospheres (HAuNS). We demonstrated the specific binding and selective toxicity of the system to HER2-positive tumor cells in co-cultures of HER2-positive and -negative cells. Furthermore, the HER2-antibody-mediated delivery of targeted liposomes was confirmed in a double-tumor model in nude mice simultaneously bearing HER2-positive and -negative tumors. This induced a >2-fold increased accumulation in the tumors with positive expression of HER2 than that with non-targeted liposomes (no HER2-antibody conjugation). The combination of targeted liposomes with NIR laser irradiation had significant antitumor activity in vivo with the tumor inhibition efficiency up to 92.7%, attributed to the increased accumulation in tumors and the double efficacy of photothermal-chemotherapy. Moreover, targeted liposomes did not cause systemic toxicity during the experiment period, attributable to the reduced dose of DOX, the decreased accumulation of liposomes in normal tissues, and the low irradiation power. The targeted liposomes provide a multifunctional nanotechnology platform for antibody-mediated delivery, light-trigged drug release, and combined photothermal-chemotherapy, which may have potential in the clinical treatment of cancer.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Qingpo
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry, School of Medicine, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Peizun
authors.initials: P
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Zuhua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, School of Medicine, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhao
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, School of Medicine, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biochemistry, School of Medicine, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Hu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Du
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Biochemistry, School of Medicine, Zhejiang University, 310058 Hangzhou, China. Electronic address: jzhan2k@zju.edu.cn.
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Zhan
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China. Electronic address: youjiandoc@zju.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: You
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D018796:Immunoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D008027:Light; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010789:Phototherapy; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004317:Doxorubicin; D018796:Immunoconjugates; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; C506643:liposomal doxorubicin; C508053:ERBB2 protein, human
keywords: Antibody-mediated targeted delivery; HER2 antibody; Hollow gold nanospheres; Light-sensitive liposomes; Photothermal-chemotherapy