title: Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA.
abstract: We developed, synthesized, and tested a multifunctional nanostructured lipid nanocarrier-based system (NLCS) for efficient delivery of an anticancer drug and siRNA directly into the lungs by inhalation. The system contains: (1) nanostructured lipid carriers (NLC); (2) anticancer drug (doxorubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) siRNA targeted to BCL2 mRNA as a suppressor of nonpump cellular resistance and (5) a modified synthetic analog of luteinizing hormone-releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells. The NLCS was tested in vitro using human lung cancer cells and in vivo utilizing mouse orthotopic model of human lung cancer. After inhalation, the proposed NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact and also significantly decreasing the exposure of healthy organs when compared with intravenous injection. The NLCS showed enhanced antitumor activity when compared with intravenous treatment. The data obtained demonstrated high efficiency of proposed NLCS for tumor-targeted local delivery by inhalation of anticancer drugs and mixture of siRNAs specifically to lung cancer cells and, as a result, efficient suppression of tumor growth and prevention of adverse side effects on healthy organs.
authors: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Piscataway 08854, USA; Department of Pharmaceutical Sciences, Oregon State University, Corvallis 97331, USA.
authors: Oleh
authors: O
authors: Taratula
authors: Andriy
authors: A
authors: Kuzmov
authors: Milin
authors: M
authors: Shah
authors: Olga B
authors: OB
authors: Garbuzenko
authors: Tamara
authors: T
authors: Minko
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D004337:Drug Carriers; D007987:Gonadotropin-Releasing Hormone; D008055:Lipids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C421109:multidrug resistance-associated protein 1
keywords: Drug resistance; Imaging; Inhalation; Luteinizing hormone-releasing hormone (LHRH); Nanostructured lipid carrier; Orthotopic lung cancer model
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