RESUMO
Objective: To establish the technique of intratumoral combination therapy of radiofrequency hyperthermia (RFH) with herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy for rat ovarian cancers.Material and methods: This study consisted of three parts: (1) in vitro experiments to establish the 'proof of principal' that combination of RFH and HSV-TK gene therapy has the synergistic effect on human ovarian cancer cells; (2) creation of bioluminescence imaging-detectable rat ovarian cancer model; and (3) in vivo experiments using this rat model to validate the technical feasibility of the combination therapy. Cells and nude rats were divided into four groups: (i) combination therapy (HSV-TK/GCV + RFH); (ii) RFH; (iii) HSV-TK/GCV; and (iv) phosphate-buffered saline (PBS). Data were analyzed using Dunnett t-test or Kruskal-Wallis test.Results: Cell proliferation assay demonstrated significantly greater reduction in viable cells with the combination therapy [0.52 (0.43, 0.61)] compared to other treatments [RFH 0.90 (0.84, 0.96), HSV-TK/GCV 0.71 (0.53, 0.88), PBS 1 (1, 1); p < .05]. For 24 rat models with bioluminescence imaging-detectable orthotopic ovarian cancer (n = 6 per group), optical imaging demonstrated significantly decreased relative bioluminescence signal with the combination therapy [0.81 (0.52, 1.08)] compared to other treatments [RFH 3.60 (2.34, 4.86), HSV-TK/GCV 2.21 (1.71, 2.71), PBS 3.74 (3.19, 4.29); p < .001]. Ultrasound imaging demonstrated the smallest relative tumor volume with the combination therapy [0.78 (0.45, 1.11) versus 3.50 (2.67, 4.33), 2.10 (0.83, 3.37), 3.70 (1.79, 5.61); p < .05].Conclusion: The feasibility of intratumoral RFH-enhanced HSV-TK/GCV gene therapy was established on a unique rat model with molecular imaging-detectable orthotopic ovarian cancer.
Assuntos
Terapia Genética/métodos , Hipertermia Induzida/métodos , Imagem Molecular/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/radioterapia , Simplexvirus/efeitos dos fármacos , Timidina Quinase/uso terapêutico , Animais , Feminino , Humanos , Ratos , Ratos Nus , Timidina Quinase/farmacologiaRESUMO
Photovoltaic (PV) materials such as perovskites and silicon are generally unabsorptive at wavelengths longer than 1100 nm, leaving a significant portion of the IR solar spectrum unharvested. Small-bandgap colloidal quantum dots (CQDs) are a promising platform to offer tandem complementary IR PV solutions. Today, the best performing CQD PVs use zinc oxide (ZnO) as an electron-transport layer. However, these electrodes require ultraviolet (UV)-light activation to overcome the low carrier density of ZnO, precluding the realization of CQD tandem photovoltaics. Here, a new sol-gel UV-free electrode based on Al/Cl hybrid doping of ZnO (CAZO) is developed. Al heterovalent doping provides a strong n-type character while Cl surface passivation leads to a more favorable band alignment for electron extraction. CAZO CQD IR solar cell devices exhibit, at wavelengths beyond the Si bandgap, an external quantum efficiency of 73%, leading to an additional 0.92% IR power conversion efficiency without UV activation. Conventional ZnO devices, on the other hand, add fewer than 0.01 power points at these operating conditions.