Hybrid Theranostic Platform for Second Near-IR Window Light Triggered Selective Two-Photon Imaging and Photothermal Killing of Targeted Melanoma Cells.

Despite advances in the medical field, even in the 21st century cancer is one of the leading causes of death for men and women in the world. Since the second near-infrared (NIR) biological window light between 950 and 1350 nm offers highly efficient tissue penetration, the current article reports the development of hybrid theranostic platform using anti-GD2 antibody attached gold nanoparticle (GNP) conjugated, single-wall carbon nanotube (SWCNT) for second near-IR light triggered selective imaging and efficient photothermal therapy of human melanoma cancer cell. Reported results demonstrate that due to strong plasmon-coupling, two-photon luminescence (TPL) intensity from theranostic GNP attached SWCNT materials is 6 orders of magnitude higher than GNP or SWCNT alone. Experimental and FDTD simulation data indicate that the huge enhancement of TPL intensity is mainly due to strong resonance enhancement coupled with the stronger electric field enhancement. Due to plasmon coupling, the theranostic material serves as a local nanoantennae to enhance the photothermal capability via strong optical energy absorption. Reported data show that theranostic SWCNT can be used for selective two-photon imaging of melanoma UACC903 cell using 1100 nm light. Photothermal killing experiment with 1.0 W/cm(2) 980 nm laser light demonstrates that 100% of melanoma UACC903 cells can be killed using theranostic SWCNT bind melanoma cells after just 8 min of exposure. These results demonstrate that due to plasmon coupling, the theranostic GNP attached SWCNT material serves as a two-photon imaging and photothermal source for cancer cells in biological window II.

Ascorbic Acid Potentiation of Arsenic Trioxide Anticancer Activity Against Acute Promyelocytic Leukemia.

INTRODUCTION: Acute promyelocytic leukemia (APL) is a malignant disorder of the white blood cells. Arsenic trioxide (As(2)O(3)) has been used as a therapeutic agent to treat APL and other tumors. Studies suggest that ascorbic acid (AA) supplementation may improve the clinical outcome of As(2)O(3) for APL patients. Our aim was to use human leukemia (HL-60) APL-cells as an in vitro test model to evaluate the effect of physiologic doses of AA on As(2)O(3)-induced toxicity and apoptosis of HL-60 cells. METHODS: HL-60 cells were treated either with a pharmacologic dose of As(2)O(3) alone and with several physiologic doses of AA. Cell survival was determined by trypan blue exclusion test. The extent of oxidative cell/tissue damage was determined by measuring lipid hydroperoxide concentration by spectrophotometry. Cell apoptosis was measured by flow cytometry using Annexin-V and propidium iodide (PI) staining. RESULTS: AA treatment potentiates the cytotoxicity of As(2)O(3) in HL-60 cells. Viability decreased from (58 +/- 3)% in cells with As(2)O(3) alone to (47 +/- 2)% in cells treated with 100 microM AA and 6 microg/mL As(2)O(3) with P < 0.05. There was a significant (P < 0.05) increase in lipid hydroperoxide concentrations in HL-60 cells co-treated with AA compared to As(2)O(3) alone. Flow cytometry assessment (Annexin V FITC/PI) suggested that AA co-treatment induces more apoptosis of HL-60 cells than did As(2)O(3) alone, but this was not statistically significant. Taken together, our experiment indicates that As(2)O(3) induced in vitro cell death and apoptosis of HL-60 cells. Administration of physiologic doses of AA enhanced As(2)O(3)-induced cytotoxicity, oxidative cell/tissue damage, and apoptosis of HL-60 cells through externalization of phosphatidylserine. CONCLUSIONS: These suggest that AA may enhance the cytotoxicity of As(2)O(3), suggesting a possible future role of AA/As(2)O(3) combination therapy in patients with APL.