At left is the new nanodevice, consisting of a hydrogel embedded with gold nanoparticles coated with DNA targeting a gene called MRP-1. At right, the device fluoresces after encountering the target gene sequence.
A tumor’s developing drug resistance is driven in large part by its genome, which has mechanisms to protect cancer cells from chemical attacks and apoptosis. Researchers at MIT are using nanoparticles made out of gold specs surrounded by a hydrogel to turn off tumors’ ability to develop drug resistance by inactivating specific genes.
The researchers tested the therapeutic approach on a triple negative breast tumor that is normally very difficult to treat. The tumor contains a gene that codes for the multidrug resistant protein 1 (MRP1) that activates a mechanism within the cell that pushes chemo drugs back out, effectively making the tumor drug resistant. The MIT nanodevice has a molecular complement to the MRP1 gene that binds to and blocks the expression of this gene while delivering a dose of chemo drug 5-fluorouracil, destroying the tumor’s defense system while stabbing it with a toxic strike. Within their laboratory study, the researchers were able to shrink triple negative breast tumor by 90% within two weeks.
Some more details about the technology according to the abstract in Proceedings of the National Academy of Sciences:
Our platform contains hydrogel embedded with dark-gold nanoparticles modified with 5-fluorouracil (5-FU)-intercalated nanobeacons that serve as an ON/OFF molecular nanoswitch triggered by the increased MRP1 expression within the tumor tissue microenvironment. This nanoswitch can sense and overcome MDR prior to local drug release. The nanobeacons comprise a 5-FU intercalated DNA hairpin, which is labeled with a near-infrared (NIR) dye and a dark-quencher. The nanobeacons are designed to open and release the intercalated drug only upon hybridization of the DNA hairpin to a complementary target, an event that restores fluorescence emission due to nanobeacons conformational reorganization.
Study in Proceedings of the National Academy of Sciences: Implantable hydrogel embedded dark-gold nanoswitch as a theranostic probe to sense and overcome cancer multidrug resistance…
Source: MIT…