Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells.
Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain reaction results showed that dextran nanoparticles could deliver both miR-199a-3p and let-7a into osteosarcoma cell lines (KHOS and U-2OS) successfully. Western blotting analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that dextran nanoparticles loaded with miRs could efficiently downregulate the expression of target proteins and effectively inhibit the growth and proliferation of osteosarcoma cells. These results demonstrate that a lipid-modified dextran-based polymeric nanoparticle platform may be an effective nonviral carrier for potential miR-based anticancer therapeutics.
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA ; Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Linlin
L
Zhang
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, USA ; Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
Arun K
AK
Lyer
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Xiaoqian
X
Yang
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Eisuke
E
Kobayashi
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA ; Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Yuqi
Y
Guo
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Henry
H
Mankin
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Francis J
FJ
Hornicek
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, USA.
Mansoor M
MM
Amiji
Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Zhenfeng
Z
Duan
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry*; D012516:Osteosarcoma
D004337:Drug Carriers; D035683:MicroRNAs; C531408:mirn199 microRNA, human
RNAi; bone tumor; dextran nanoparticles; let-7a; miR-199a-3p