System:
γ-eye
Sukhvir Kaur Bhangu, Soraia Fernandes, Giovanni Luca Beretta, Stella Tinelli,Marco Cassani, Agata Radziwon, Marcin Wojnilowicz, Sophia Sarpaki, Irinaios Pilatis,Nadia Zaffaroni, Giancarlo Forte, Frank Caruso, Muthupandian Ashokkumar, and Francesca Cavalieri
According to the National Cancer Institute within the NIH, approximately 40.5% of men and women will be diagnosed with cancer at some point during their lifetimes. Depending on the type and stage of cancer, chemotherapy is a commonly used treatment for cancer patients. Chemotherapy targets cells that grow rapidly, which cancer cells do, however chemotherapy may also affect normal, quickly growing cells, such as hair follicles.
Reconfiguring the chemical structure and selectivity of existing chemotherapy drugs presents an opportunity to selectively kill cancer cells. Utilizing a conventional anticancer drug Doxorubicin and ultrasound, researchers were able to alter the structure of Doxorubicin to create a nanodrug that selectively targets and destroys various cancer cells. The nanodrug’s selective action is attributed to its strong interaction with the mitochondria of cancer cells. This leads to elevated levels of reactive oxygen species which leads to subsequent cell death.
In vivo biodistribution studies showed accumulation of the nanodrug within the lungs and limited accumulation in the liver and spleen. In addition, the nanodrug imparted negligible toxicity towards healthy cells like fibroblasts, while killing cancer cells, even those resistant to treatment with Doxorubicin. As such, these results indicate increased selectivity of the nanodrug for cancer cells. This study highlights the potential of transforming anticancer drugs to nanodrugs as a promising platform to selectively kill cancer cells.
Figure 1: Engineering DOX into a stable nanodrug. a) Schematic of the ultrasound-assisted engineering of DOX into NDDOX. A solution of DOX in water (0.5 mg mL−1) was sonicated at high frequency (490 kHz) and 2 W cm−2 for 3 h to readily form NDDOX. DOX is converted into hydroxylated species (MonA and DimA) (i) at the transient cavitation bubble/solution interface (ii) and subsequently the products self-assemble upon bubble collapse to form uniform DDOX nanoparticles (iii). b) Representative STORM image of NDDOX labeled with the photoswitchable dye AF 647; the inset shows a magnified view of a single NDDOX nanoparticle. The results are from three independent experiments. c) AFM (height 0–10 nm), d) SEM, and e) TEM images of NDDOX nanoparticles, respectively. f) The size distribution of NDDOX in aqueous solution, determined using DLS. g) Dissolution kinetics of NDDOX at pH 5 and pH 7.4 in 100 × 10−3 m PBS, 100% FBS, and cell culture medium Dulbecco’s modified Eagle medium containing 10% FBS. The % release was determined by measuring fluorescence emission (λ520nm) of the collected supernatant after centrifugation of NDDOX. h) Scheme showing the adsorption of protein on the surface of NDDOX after incubation with FBS and STORM images of the NDDOX acquire after 8 h incubation with 10% and 100% FBS. Results are from three independent experiments.
