Uptake and localization of nanoparticles in prostate and lung cancer cells as a function of time and nanoparticle type
Mentor: Wilfred Ngwa, Ph.D. (Dana Farber Cancer Institute)
Nanoparticles of varying materials (gold, titanium dioxide, graphene oxide etc.) have been shown to have radio-/photo-sensitizing properties. These sensitizers increase sensitivity of cancer cells to damage during radiation therapy. By implanting a nanoparticle-loaded radiation therapy biomaterial (RTB), such as a fiducial, into the tumor, nanoparticles can be released in situ. This method can lead to local damage enhancement while sparing healthy tissue. Use of a RTB for delivery of nanoparticles also allows for sustained release of nanoparticles directly into the tumor environment minimizing systemic toxicities. Cellular uptake of nanoparticles is primarily facilitated via receptor-mediated endocytosis.. Gold, titanium dioxide, and graphene oxide nanoparticles in conjunction with radiotherapy have been shown to disrupt the cellular function of tumors via the induction of reactive oxygen species (ROS). This leads to oxidative stress and the release of cytochrome c which causes apoptosis. The nuclear pore size exclusion for the diffusion of molecules is around 9 nm. Thus, nanoparticles larger than 9 nm have been shown to accumulate primarily in the cytosol while smaller molecules are able to enter the nuclear space. It is important to understand the localization of various nanoparticles as a function of time in order to determine the most effective timing of exposing the tumor to radiation. This can be accomplished by treating cancer cells with nanoparticles and using electron microscopy to determine localization over the course of time.
Electron microscopy images of (A) untreated RAW 264.7 cells and the subcellular localization of (B) TiO2 and (C) carboxylated and (D) amino (NH2) polystyrene (PS) nanospheres. Labels: M=mitochondria, P=particles. Source: http://www1.cnsi.ucla.edu/arr/paper?paper_id=192734 Source: