Survivin-miRNA-loaded nanoparticles as auxiliary tools for radiation therapy: preparation, characterisation, drug release, cytotoxicity and therapeutic effect on colorectal cancer cells.
One of the main challenges in radiation oncology is to overcome the resistance of cancer cells against treatment by molecular targeted approaches. Among the most promising targets is the inhibitor of apoptosis protein survivin, known to be associated with increased tumour aggressiveness and therapy resistance. The objective of this study was the development of a human serum albumin-based nanoparticulate carrier system for plasmid-mediated RNA interference (miRNA) and the investigation of its in vitro efficacy on survivin knockdown and cellular toxicity in SW480 colorectal cancer cells. The results demonstrate a robust nanoparticulate system of a size around 220 nm with a plasmid incorporation efficacy of about 90%. Moreover, treatment of carcinoma cells with survivin-miRNA nanoparticles resulted in reduction of survivin expression by 50% and increased cytotoxicity if combined with ionising irradiation. These nanoparticles comprise a promising option to enhance the response of carcinoma cells to therapy with ionising irradiation.
Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
Sebastian
S
Gaca
Sebastian
S
Reichert
Claus
C
Rödel
Franz
F
Rödel
Jörg
J
Kreuter
D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs / Q000737:chemistry / Q000494:pharmacology*; D053758:Nanoparticles; D010316:Particle Size; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D011838:Radiation-Sensitizing Agents; D012709:Serum Albumin; D000077022:Survivin