RNAi-based glyconanoparticles trigger apoptotic pathways for in vitro and in vivo enhanced cancer-cell killing

• Published in: Nanoscale Vol. 7; no. 19; pp. 9083 - 9091
• Main Authors: Conde, João, Tian, Furong, Hernandez, Yulan, Bao, Chenchen, Baptista, Pedro V, Cui, Daxiang, Stoeger, Tobias, de la Fuente, Jesus M
• Format: Journal Article
• Language: English
• Published: England 21.05.2015
• Subjects: Animals; Apoptosis; Biotechnology; Cell Line, Tumor; Cell Proliferation; fas Receptor - genetics; fas Receptor - metabolism; Female; Glucose - chemistry; Gold - chemistry; Immunohistochemistry; Inflammatory response; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Materials science; Metal Nanoparticles - chemistry; Mice; Nanostructure; Optical Imaging; Polyethylene Glycols - chemistry; Proto-Oncogene Proteins c-myc - antagonists & inhibitors; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Reduction; RNA Interference; RNA, Small Interfering - chemistry; RNA, Small Interfering - metabolism; Surgical implants; Tomography, X-Ray Computed; Tumours
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c4nr05742b

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.