Ag NP are effective photothermal agents. A secondary benefit is the differential response of breast cancer cells to Ag NP-induced hyperthermia, due to increased intracellular silver content, compared to non-tumorigenic breast epithelial cells.
The photothermal efficiency of two similar organic nanomaterials, poly(3,4-ethylenedioxythiophene):poly(4-styrene-sulfonate) (PEDOT:PSS) nanoparticles and poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes, are compared. The PEDOT:PSS nanoparticles ranged from 100-200 nm in diameter, while the PEDOT nanotubes ranged from 200-400 nm in diameter and 4-10 microm in length. By changing the aspect ratio of the PEDOT nanomaterials from a spherical to a tubular shape, interesting differences in the optical and electronic properties of the materials were realized. Because of this, the PEDOT nanotubes were shown to generate on average approximately to 10 degrees C better internal heating for similar concentrations compared to the PEDOT:PSS nanoparticles. Cytotoxicity studies of both nanomaterials showed no significant toxicity towards RKO or HCT116 colorectal cancer cells in the absence of NIR light. The NIR-mediated photothermal efficiency of the PEDOT:PSS nanoparticles and the PEDOT nanotubes were compared in-vitro. A cell viability assay was performed and at the highest concentration (0.1 mg/mL) of nanomaterial, cell survival was close to 20% for the PEDOT:PSS nanoparticles with both RKO and HCT116 cells. Consequently, cell survival for the PEDOT nanotubes was less than 5% for both RKO and HCT116 cells. An in-vitro three dimensional tumor model was assembled using collagen gel tissue phantoms. The depth of heat penetration from the PEDOT nanotubes into the tissue phantoms, along with cell viability of RKO and HCT116 cells was determined and quantified.
Lesion-based targeting strategies underlie cancer precision medicine. However, biological principlessuch as cellular senescenceremain difficult to implement in molecularly informed treatment decisions. Functional analyses in syngeneic mouse models and crossspecies validation in patient datasets might uncover clinically relevant genetics of biological response programs. Here, we show that chemotherapy-exposed primary Eµ-myc transgenic lymphomaswith and without defined genetic lesionsrecapitulate molecular signatures of patients with diffuse large B-cell lymphoma (DLBCL). Importantly, we interrogate the murine lymphoma capacity to senesce and its epigenetic control via the histone H3 lysine 9 (H3K9)methyltransferase Suv(ar)39h1 and H3K9me3-active demethylases by loss-and gain-offunction genetics, and an unbiased clinical trial-like approach. A mouse-derived senescenceindicating gene signature, termed "SUVARness", as well as high-level H3K9me3 lymphoma expression, predict favorable DLBCL patient outcome. Our data support the use of functional genetics in transgenic mouse models to incorporate basic biology knowledge into cancer precision medicine in the clinic.
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