title: Targeted delivery of doxorubicin to breast cancer cells by aptamer functionalized DOTAP/DOPE liposomes.
abstract: Doxorubicin is used to treat numerous types of tumors including breast cancer, yet dose-associated toxicities limit its clinical application. Here, we demonstrated a novel strategy by which to deliver doxorubicin to breast cancer cells by conjugating cancer cell-specific single-strand DNA aptamers with doxorubicin-encapsulated DOTAP:DOPE nanoparticles (NPs). We utilizing a whole-cell-SELEX strategy, and 4T1 cells with high invasive and metastatic potential were used as target cells, while non-invasive and non-metastatic 67NR cells were used as subtractive cells. Ten potential aptamers were generated after multi-pool selection. Studies on the selected aptamers revealed that SRZ1 had the highest and specific binding affinity to 4T1 cells. Then we developed SRZ1 aptamer-carried DOTAP:DOPE-DOX NPs. In vitro uptake results which were conducted by FACS indicated that the aptamer significantly promoted the uptake efficiency of DOTAP:DOPE-DOX NPs by 4T1 cells. ATPlite assay was performed to test 4T1, 67NR and NMuMG cell viability after treatment with free doxorubicin, DOTAP:DOPE-DOX particles and aptamer‑loaded DOTAP:DOPE-DOX particles. As expected, the aptamers effectively enhanced accumulation of doxorubicin in the 4T1 tumor tissues as determined by in vivo mouse body images and biodistribution analysis. Consistent with the in vitro findings, aptamer-conjugated doxorubicin-loaded DOTAP:DOPE particles markedly suppressed tumor growth and significantly increased the survival rate of 4T1 tumor-bearing mice. These studies demonstrated that aptamer SRZ1 could be a promising molecule for chemotherapeutic drug targeting deliver.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Breast Surgery, Xuzhou Tumor Hospital, Xuzhou, Jiangsu, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Beijing Aerospace General Hospital, Beijing, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, P.R. China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhen
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000008:administration & dosage; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage; D052156:SELEX Aptamer Technique; D023041:Xenograft Model Antitumor Assays
chemical_list: D005229:Fatty Acids, Monounsaturated; D008081:Liposomes; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; C094877:dioleoyl phosphatidylethanolamine; D004317:Doxorubicin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane