Design and in vitro evaluation of layer by layer siRNA nanovectors targeting breast tumor initiating cells.
Efficient therapeutics and early detection has helped to increase breast cancer survival rates over the years. However, the recurrence of breast cancer remains to be a problem and this may be due to the presence of a small population of cells, called tumor initiating cells (TICs). Breast TICs are resistant to drugs, difficult to detect, and exhibit high self-renewal capabilities. In this study, layer by layer (LBL) small interfering RNA (siRNA) nanovectors (SNVs) were designed to target breast TICs. SNVs were fabricated using alternating layers of poly-L-lysine and siRNA molecules on gold (Au) nanoparticle (NP) surfaces. The stability, cell uptake, and release profile for SNVs were examined. In addition, SNVs reduced TIC-related STAT3 expression levels, CD44+/CD24-/EpCAM+ surface marker levels and the number of mammospheres formed compared to the standard transfection agent. The data from this study show, for the first time, that SNVs in LBL assembly effectively delivers STAT3 siRNA and inhibit the growth of breast TICs in vitro.
Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
Hamsa
H
Jaganathan
Cancer Center of Excellence, Houston Methodist Research Institute, Houston, Texas, United States of America.
Sucharita
S
Mitra
Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
Srimeenakshi
S
Srinivasan
Cancer Center of Excellence, Houston Methodist Research Institute, Houston, Texas, United States of America.
Bhuvanesh
B
Dave
Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
Biana
B
Godin
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D005822:Genetic Vectors; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles; D011107:Polylysine / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics
D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D011107:Polylysine; D006046:Gold