Rice researchers found that chemotherapy agents attached to nanotubes are too large to go through the pores of normal blood vessels (left), but small enough to pass through the pores of cancer-related vessels. Once through, the customized nanotubes can be taken up by cancer cells to deliver their therapeutic cargoes. Courtesy of Rei Suzuki/University of Texas MD Anderson Cancer Center)
Pancreatic cancer is a vicious disease that attacks its victims with great speed, is hard to detect, and for which meaningful therapies are nearly nonexistent. Getting chemo drugs to reach pancreatic tumor cells with precision is a challenge. To overcome this, researchers at Rice University and MD Anderson Cancer Center have been testing a method that relies on carbon nanotubes to deliver chemo precisely into cancer cells, and then onward into the cells’ nuclei.
Laser confocal microscopy images show nanotubes combined with polyethyleneimine and fluorescent tags can be taken up by pancreatic cancer cells. The top image shows nanotubes with rhodamine B dye in the cells; the center image shows a DAPI-stained cell and the bottom image combines the two. Courtesy of Enrico Andreoli/Barron Group
The scientists used a technique called functionalization, which allows chemo agents to be attached to the nanotubes. Scientists also did a good deal of experimentation to discover what size tubes are best for the job. Turns out that 50 nanometers in length was ideal.
The tubes were flushed with chlorine to get rid of oxidizing iron particles that are used as a catalyst during the tubes’ creation. Additionally, the nanotubes had a polyethyleneimine (PEI) coating added to their surface, helping the tubes disperse and pass through cells walls and into the nucleus. Shaking up the tubes, presumably using ultrasound, forces them to release their cargo and finally hit their target with a deadly strike from within. The researchers plan to begin testing the new technology on mice who will have allografts of human tumors transplanted into them.
Some details from the study abstract:
High quality single-walled carbon nanotubes (SWNTs) were obtained following a new purification procedure, based on using Cl2 gas at high temperature. Cl2-treated SWNTs were fluorinated and modified with branched polyethyleneimine (PEI) to afford covalently functionalised PEI-SWNTs, which were then tested for cytotoxicity both in vitro (HPNE and BxPC3 pancreatic cell lines) and in vivo (BxPC3 xenografts from nude mice) to establish that functionalization with lower molecular weight PEI (600 and 1800 Da) achieved higher cell viability in MTT assay. A shortened version of the nanotubes, PEI(1800)-cut-SWNT (1800 Da branched PEI), was also prepared and tested for cellular internalization in BxPC3 adenocarcinoma cell line. Laser confocal imaging of the cells after incubation in the presence of RhoB-PEI(1800)-cut-SWNT (covalently labelled with rhodamine B) indicates that the PEI(1800)-cut-SWNTs can reach both the cytoplasm and nucleus of pancreatic cancer cells.
Study in Journal of Material Chemistry B: Preparation and evaluation of polyethyleneimine-single walled carbon nanotube conjugates as vectors for pancreatic cancer treatment…
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