title: Dual-targeting nanocarrier system based on thermosensitive liposomes and gold nanorods for cancer thermo-chemotherapy.
abstract: The primary challenge of cancer therapy was the failure of most chemotherapeutics to accumulate in the tumors, additionally causing serious systemic side effects. We designed a tumor-targeting accumulated and locally triggered-release nanocarrier system to increase the intratumoral drug concentration and thus the efficacy of chemotherapy, based on gold nanorods (GNRs) and thermosensitive liposomes (TSLs). PEGylated GNRs could not only make nanocarriers to co-accumulate in tumors depending on enhanced permeability and retention (EPR) effect, but also generated heat locally under near-infrared (NIR) stimulation. CO2 bubbles were generated by the encapsulated ammonium bicarbonate (ABC) under hyperthermia, thus the co-encapsulated drug was released and local drug concentration was increased along with the disintegration of liposomal membrane. On the other hand, this dual-targeting system prevented the drug leakage in blood circulation or other organs while facilitated most of the active agents delivered to tumors. In vitro and in vivo experiments revealed high cytotoxicity and good affinity of HTSL to MDA-MB-435 cells when used synergistically with GNRs, but low toxicity to normal cells at the same condition. When combined with thermotherapy, the smart nanocarrier system held significant promise for future cancer treatment for their markedly improved therapeutic efficacy and decreased systemic toxicity.
authors.affiliation: Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China. Electronic address: tanfengping@163.com.
authors.forename: Fengping
authors.initials: F
authors.lastname: Tan
authors.affiliation: Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, PR China. Electronic address: linan19850115@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001639:Bicarbonates / Q000737:chemistry; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006046:Gold; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D043942:Nanotubes; D011092:Polyethylene Glycols
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001639:Bicarbonates; D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D002245:Carbon Dioxide; D011092:Polyethylene Glycols; C027043:ammonium bicarbonate; D006046:Gold; D004317:Doxorubicin
keywords: Dual-targeting; Gold nanorod; Photothermally triggered release; Thermo-chemotherapy; Thermoresponsive liposome