PLGA-carbon nanotube conjugates for intercellular delivery of caspase-3 into osteosarcoma cells

• Published in: PloS one 2013-12, Vol.8 (12), p.e81947
• Main Authors: Cheng, Qingsu, Blais, Marc-Olivier, Harris, Greg M, Harris, Greg, Jabbarzadeh, Ehsan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Biocompatibility; Biomedical materials; Bone cancer; Cancer; Cancer cells; Cancer therapies; Carbon nanotubes; Caspase; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Caspases; Cattle; Cell fate; Cell Line, Tumor; Cell proliferation; Conjugates; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Extracellular Space - metabolism; Gene transfer; Genetic vectors; Health aspects; Health care; Humans; Lactic Acid - chemistry; Medical personnel; Nanotechnology; Nanotubes; Nanotubes, Carbon - chemistry; Osteosarcoma; Osteosarcoma - pathology; Osteosarcoma cells; Permeability; Physicians; Physiological aspects; Polyglycolic Acid - chemistry; Polylactide-co-glycolide; Sarcoma; Side effects; Toxicity; Transfection - methods; Tumors; Vectors (Biology)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081947

Cancer has arisen to be of the most prominent health care issues across the world in recent years. Doctors have used physiological intervention as well as chemical and radioactive therapeutics to treat cancer thus far. As an alternative to current methods, gene delivery systems with high efficiency, specificity, and safety that can reduce side effects such as necrosis of tissue are under development. Although viral vectors are highly efficient, concerns have arisen from the fact that viral vectors are sourced from lethal diseases. With this in mind, rod shaped nano-materials such as carbon nanotubes (CNTs) have become an attractive option for drug delivery due to the enhanced permeability and retention effect in tumors as well as the ability to penetrate the cell membrane. Here, we successfully engineered poly (lactic-co-glycolic) (PLGA) functionalized CNTs to reduce toxicity concerns, provide attachment sites for pro-apoptotic protein caspase-3 (CP3), and tune the temporal release profile of CP3 within bone cancer cells. Our results showed that CP3 was able to attach to functionalized CNTs, forming CNT-PLGA-CP3 conjugates. We show this conjugate can efficiently transduce cells at dosages as low as 0.05 μg/ml and suppress cell proliferation up to a week with no further treatments. These results are essential to showing the capabilities of PLGA functionalized CNTs as a non-viral vector gene delivery technique to tune cell fate.