ICG-loaded gold nano-bipyramids with NIR activatable dual PTT-PDT therapeutic potential in melanoma cells
COLLOIDS AND SURFACES B-BIOINTERFACES
Authors: Campu, Andreea; Focsan, Monica; Lerouge, Frederic; Borlan, Raluca; Tie, Leopold; Rugina, Dumitrita; Astilean, Simion
Abstract
A great amount of effort is directed towards the progress of cancer treatment approaches aspiring to develop non-invasive, targeted and highly efficient therapies. In this context, Photothermal (PTT) and Photodynamic (PDT) Therapies were proven as promising. This work aims to integrate the therapeutic activities of two nearinfrared (NIR) photoactive biomaterials -gold nano-bipyramids (AuBPs) and Indocyanine Green (ICG) -into one single targeted hybrid nanosystem able to operate as dual PTT-PDT agent with higher efficiency compared with each one alone. Firstly, different aspect ratio' AuBPs were systematically investigated in water solution for their intrinsic ability to efficiently generate toxic reactive oxygen species, namely oxygen singlet (O-1(2)), under NIR laser irradiation, as this effect is less investigated in literature. Interestingly, the photodynamic activity of AuBPs measured by monitoring the photooxidation of 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA) - a well-known O-1(2) sensor, is important, counting for 30 % decrease in ABDA optical absorbance for the most active AuBPs, well-correlating with the previously determined photothermal conversion efficiency. Furthermore, ICG was successfully grafted onto the Poly-lactic acid (PLA) coating of plasmonic nanoparticles and, consequently, the as-designed fully integrated hybrid nanosystem shows improved PTT-PDT performance in solution. Specifically, by triggering simultaneous PTT-PDT activities, the O-1(2) amount is doubled, while the heating monitoring shows higher and faster increase in temperature compared to AuBPs alone. Finally, the efficiency of the combined PTT-PDT therapeutic activity was validated in vitro against B16-F10 cell line by covalent conjugation of the nanosystem with Folic Acid, which ensures the cellular recognition by overexpression of folate receptor.
Luteolin, an aryl hydrocarbon receptor ligand, suppresses tumor metastasisin vitroandin vivo
ONCOLOGY REPORTS
Authors: Feng, Jinhong; Zheng, Ting; Hou, Zhaohua; Lv, Cui; Xue, Anqi; Han, Tingting; Han, Beibei; Sun, Xin; Wei, Yunbo
Abstract
Estrogen receptor (ER)-negative breast tumors are associated with low survival rates, which is related to their ability to grow and metastasize into distal organs. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that is involved in several biological processes, is a promising anti-metastatic target. Luteolin, a non-toxic naturally occurring plant flavonoid with diverse biological activities, has been demonstrated to be effective against certain types of cancer, and has also been described as a ligand of AhR. In the present study, various cancer cell lines were first investigated following treatment with luteolin, and luteolin exhibited the lowest IC(50)in MDA-MB-231 cells. Then, the efficiency of luteolin in suppressing the metastasis of ER-negative breast cancerin vitrowas assessed. MDA-MB-231 cells were treated with luteolinin vitro. Subsequently, MTT assay and flow cytometry were used to detect cell viability, the cell cycle and apoptosis, and a Transwell assay was used to evaluate cell invasion. In addition, reverse transcription-semi-quantitative PCR and western blot were performed to detect the mRNA and protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. In addition, the number of surface tumor nodules was measuredin vivo, in mice bearing B16-F10 tumors, following treatment with luteolin. Luteolin inhibited the viability and induced the apoptosis of MDA-MB-231 cells, which was accompanied by cell cycle arrest. This was associated with a decrease in the expression of the pro-metastatic markers C-X-C chemokine receptor type 4 (CXCR4), MMP-2 and MMP-9, which was reversed by AhR inhibition. Furthermore, it was identified that luteolin could inhibit the metastasis in a B16F10 mouse xenograft model, and the levels of MMP-9, MMP-2 and CXCR4 were significantly decreased in the lung tissues isolated from tumor-bearing nude mice following luteolin treatment. In conclusion, luteolin is a potential molecule for inhibiting breast cancer invasion and metastasis, which could have promising clinical applications.