Carbon nanotubes as a protein toxin transporter for selective HER2-positive breast cancer cell destruction.
The recombined ricin A chain protein (RTA) was transported into living cells by multiwalled carbon nanotubes (MWNTs) as a cellular carrier, as performed by natural ricin B chain protein (RTB). The conjugate of the toxin protein RTA and MWNT was found to translocate to the cytoplasm of various cell lines and performed biological functions, as evidenced by the induction of cell death. The delivery of RTA into the cells via nanotube carriers was directly visualized by transmission electron microscopy (TEM) and confocal microscopy. About three times higher cell death rates for L-929, HL7702, MCF-7, HeLa and COS-7 cells were demonstrated induced by MWNT-RTA conjugates, compared to those achieved by RTA alone. Especially for HeLa cells, the cell mortality reached approximately 75%. In addition, obvious selective destruction of cancer cells was achieved by coupling MWNTs-RTA-HER2, which selectively recognize the HER2/neu receptor on certain breast cancer cells. This is the first example of recombined protein toxin (RTA)-induced targeting destruction for tumor cells via carbon nanotube molecular transporters. The transporting capabilities of carbon nanotubes combined with functional proteins may open exciting new venues for drug delivery and cancer therapy.
Weng
Xuexiang
X
Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, PR China.
Wang
Meiyan
M
Ge
Jing
J
Yu
Shaoning
S
Liu
Baohong
B
Zhong
Jiang
J
Kong
Jilie
J
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012276:Ricin / Q000494:pharmacology*; D013997:Time Factors; D014118:Toxins, Biological / Q000494:pharmacology*
D037742:Nanotubes, Carbon; D018719:Erb-b2 Receptor Tyrosine Kinases; D012276:Ricin; D014118:Toxins, Biological