title: The use of a tumor metastasis targeting peptide to deliver doxorubicin-containing liposomes to highly metastatic cancer.
abstract: Tumor metastasis is responsible for 90% of cancer-associated deaths and highly metastatic cancers are more prone to form metastasis foci and acquire the drug resistance. Here, a nanocarrier system (TMT-LS) has been constructed by modification of stealth liposomes with a metastatic cancer specific peptide, using the unmodified stealth liposomes (LS) as the control. The active targeted nanocarriers presented satisfactory particle size (about 100 nm) and drug release characteristics in vitro. Highly metastatic cancer cells (MDA-MB-435S and MDA-MB-231) and non-metastatic cancer cells (MCF-7) were applied as tumor cell models. The highly metastatic cancer cells were found to endocytose more TMT-LS in a faster way than TS, through a receptor-mediated pathway proved by specific receptor inhibition. Co-localization technique indicated the integrity of nanocarriers in cytoplasm. The significant targeting of TMT-LS to highly metastatic tumors was demonstrated in vivo and ex vivo in an orthotopic model as well as in a double tumor-bearing animal model with both metastatic and non-metastatic tumors in the same mouse. Importantly, the active targeted drug delivery system was found to penetrate deeper into tumor mass and have a longer retention within the malignant tissue. Further, TMT-LS greatly facilitated the efficacy of doxorubicin loaded in terms of inhibiting xenograft tumor growth and inducing cancer cell apoptosis, with only minor side effects. Together, the specific nanocarriers hold great potential in the development of nanomedicine for diagnosis and therapy of metastatic tumor.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.forename: Jingkai
authors.initials: J
authors.lastname: Lu
authors.forename: Jingrong
authors.initials: J
authors.lastname: Cui
authors.forename: Hounan
authors.initials: H
authors.lastname: Wu
authors.forename: Lan
authors.initials: L
authors.lastname: Yuan
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D004317:Doxorubicin