RNAi-Based Glyconanoparticles Trigger Apoptotic Pathways for in Vitro and in Vivo Enhanced Cancer-Cell Killing

Furong Tian, Dublin Institute of Technology
João Conde, Massachusetts Institute of Technology
Yulan Hernandez, cInstituto de Nanociencia de Aragon (INA), Universidad de Zaragoza, Zaragoza, 50018, Spain.
Chenchen Bao, dInstitute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Translation Medicine, Shanghai Jiao Tong University, Dongchuan Road 800, 200240 Shanghai, People’s Republic of China
Daxiang Cui, dInstitute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Translation Medicine, Shanghai Jiao Tong University, Dongchuan Road 800, 200240 Shanghai, People’s Republic of China
Pedro V. Baptista, UCIBIO, Departamento de Ciências da Vida, Facldade de Ciências e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal
Tobias Stoeger, bComprehensive Pneumology Centre, Institute of Lung Biology and Disease, Helmholtz Zentrum München, Neuherberg, Germany.
Jesus M. de la Fuente, Instituto de Ciencia de Materiales de Aragón-CSIC/Universidad de Zaragoza, Spain

Document Type Article

Nanoscale, 2015,7, 9083-9091

DOI: 10.1039/c4nr05742b

Abstract

Gold glyconanoparticles (GlycoNPs) are full of promise in areas like biomedicine, biotechnology and materials science due to their amazing physical, chemical and biological properties. Here, siRNA GlycoNPs (AuNP@PEG@Glucose@siRNA) in comparison with PEGylated GlycoNPs (AuNP@PEG@Glucose) were applied in vitro to a luciferase-CMT/167 adenocarcinoma cancer cell line and in vivo via intratracheal instillation directly into the lungs of B6 albino mice grafted with luciferase-CMT/167 adenocarcinoma cells. siRNA GlycoNPs but not PEGylated GlycoNPs induced the expression of pro-apoptotic proteins such as Fas/CD95 and caspases 3 and 9 in CMT/167 adenocarcinoma cells in a dose dependent manner, independent of the inflammatory response, evaluated by bronchoalveolar lavage cell counting. Moreover, in vivo pulmonary delivered siRNA GlycoNPs were capable of targeting c-Myc gene expression (a crucial regulator of cell proliferation and apoptosis) via in vivo RNAi in tumour tissue, leading to an ∼80% reduction in tumour size without associated inflammation.