Off to the Organelles - Killing Cancer Cells with Targeted Gold Nanoparticles

Abstract

Gold nanoparticles (AuNPs) are excellent tools for cancer cell imaging and basic research. However, they have yet to reach their full potential in the clinic. At present, we are only beginning to understand the molecular mechanisms that underlie the biological effects of AuNPs, including the structural and functional changes of cancer cells. This knowledge is critical for two aspects of nanomedicine. First, it will define the AuNP-induced events at the subcellular and molecular level, thereby possibly identifying new targets for cancer treatment. Second, it could provide new strategies to improve AuNP-dependent cancer diagnosis and treatment.Our review summarizes the impact of AuNPs on selected subcellular organelles that are relevant to cancer therapy. We focus on the nucleus, its subcompartments, and mitochondria, because they are intimately linked to cancer cell survival, growth, proliferation and death. While non-targeted AuNPs can damage tumor cells, concentrating AuNPs in particular subcellular locations will likely improve tumor cell killing. Thus, it will increase cancer cell damage by photothermal ablation, mechanical injury or localized drug delivery. This concept is promising, but AuNPs have to overcome multiple hurdles to perform these tasks. AuNP size, morphology and surface modification are critical parameters for their delivery to organelles. Recent strategies explored all of these variables, and surface functionalization has become crucial to concentrate AuNPs in subcellular compartments.Here, we highlight the use of AuNPs to damage cancer cells and their organelles. We discuss current limitations of AuNP-based cancer research and conclude with future directions for AuNP-dependent cancer treatment.

Shape and surface effects on the cytotoxicity of nanoparticles: Gold nanospheres versus gold nanostars

“…Although the mechanism of cell death by AuNST functionalized for targeting specific subcellular compartments such as the nucleus, and membrane deformation and cytoskeleton reorganization via macropinocytosis have been investigated, the mechanistic details of cell death for as‐synthesized AuNSTs remains unclear. Based on previous studies, it is hypothesized that the potential mechanism of cell death by the as‐synthesized AuNSTs is that the nanoparticles enter the cells via endocytosis, concentrate in the nuclei and in the cytoplasm, and induce dose‐dependent cell death via mechanical damage . Additional AuNST optimization for future research consideration is to synthesize AuNSTs with controlled size distribution, branch length and number of branched tips, and analyze the effect of these modified AuNST on cells and in native tissue.…”

Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants

“…Due to their fairly simple preparation and functionalization with drugs or other ligands, unique optical properties, and tune-ability with regards to a desired size or shape (73-75), AuNP-based immunotherapies have been a promising carrier for immune therapies in cancer antigen and immune adjuvant delivery (76-78), as well as in photothermal ablation and light triggered drug delivery (79-81). However, because AuNP can accumulate in the immune system and exhibit many toxic side effects, they should be used cautiously as a delivery system.…”

Monte Carlo simulations guided by imaging to predict the in vitro ranking of radiosensitizing nanoparticles

“…First, the radiosensitizing power of NPs is likely to be not entirely linked to the DNA damages. [16][17][18][19] Thus, the integrated or average dose deposited in the cell is an interesting information that could be correlated with the overall performance of a NP.…”