Centimetre-scale perovskite solar cells with fill factors of more than 86 per cent.

Owing to rapid development in their efficiency1 and stability2, perovskite solar cells are at the forefront of emerging photovoltaic technologies. State-of-the-art cells exhibit voltage losses3-8 approaching the theoretical minimum and near-unity internal quantum efficiency9-13, but conversion efficiencies are limited by the fill factor (<83%, below the Shockley-Queisser limit of approximately 90%). This limitation results from non-ideal charge transport between the perovskite absorber and the cell's electrodes5,8,13-16. Reducing the electrical series resistance of charge transport layers is therefore crucial for improving efficiency. Here we introduce a reverse-doping process to fabricate nitrogen-doped titanium oxide electron transport layers with outstanding charge transport performance. By incorporating this charge transport material into perovskite solar cells, we demonstrate 1-cm2 cells with fill factors of >86%, and an average fill factor of 85.3%. We also report a certified steady-state efficiency of 22.6% for a 1-cm2 cell (23.33% ± 0.58% from a reverse current-voltage scan).

In Situ Formation of Mixed-Dimensional Surface Passivation Layers in Perovskite Solar Cells with Dual-Isomer Alkylammonium Cations.

Dimensional engineering of perovskite solar cells has attracted significant research attention recently because of the potential to improve both device performance and stability. Here, a novel 2D passivation scheme for 3D perovskite solar cells is demonstrated using a mixed cation composition of 2D perovskite based on two different isomers of butylammonium iodide. The dual-cation 2D perovskite outperforms its single cation 2D counterparts in surface passivation quality, resulting in devices with an impressive open-circuit voltage of 1.21 V for a perovskite composition with an optical bandgap of ≈1.6 eV, and a champion efficiency of 23.27%. Using a combination of surface elemental analysis and valence electron spectra decomposition, it is shown that an in situ interaction between the 2D perovskite precursor and the 3D active layer results in surface intermixing of 3D and 2D perovskite phases, providing an effective combination of defect passivation and enhanced charge transfer, despite the semi-insulating nature of the 2D perovskite phase. The demonstration of the synergistic interaction of multiple organic spacer cations in a 2D passivation layer offers new opportunities for further enhancement of device performance with mixed dimensional perovskite solar cells.

Light trapping efficiency comparison of Si solar cell textures using spectral photoluminescence.

The band-to-band absorption enhancement due to various types of light trapping structures is studied experimentally with photoluminescence (PL) on monocrystalline silicon wafers. Four basic light trapping structures are examined: reactive ion etched texture (RIE), metal-assisted etched texture (MET), random pyramid texture (RAN) and plasmonic Ag nanoparticles with a diffusive reflector (Ag/DR). We also compare two novel combined structures of front side RIE/rear side RAN and front side RIE/rear side Ag/DR. The use of photoluminescence allows us to measure the absorption due to band-to-band transitions only, and excludes parasitic absorption from free carriers and other sources. The measured absorptance spectra are used to calculate the maximum generation current for each structure, and the light trapping efficiency is compared to a recently-proposed figure of merit. The results show that by combining RIE with RAN and Ag/DR, we can fabricate two structures with excellent light trapping efficiencies of 55% and 52% respectively, which is well above previously reported values for similar wafer thicknesses. A comparison of the measured band-band absorption and the EQE of back-contact silicon solar cells demonstrates that PL extracted absorption provides a very good indication of long wavelength performance for high efficiency silicon solar cells.

Nanoscale localized contacts for high fill factors in polymer-passivated perovskite solar cells.

Polymer passivation layers can improve the open-circuit voltage of perovskite solar cells when inserted at the perovskite-charge transport layer interfaces. Unfortunately, many such layers are poor conductors, leading to a trade-off between passivation quality (voltage) and series resistance (fill factor, FF). Here, we introduce a nanopatterned electron transport layer that overcomes this trade-off by modifying the spatial distribution of the passivation layer to form nanoscale localized charge transport pathways through an otherwise passivated interface, thereby providing both effective passivation and excellent charge extraction. By combining the nanopatterned electron transport layer with a dopant-free hole transport layer, we achieved a certified power conversion efficiency of 21.6% for a 1-square-centimeter cell with FF of 0.839, and demonstrate an encapsulated cell that retains ~91.7% of its initial efficiency after 1000 hours of damp heat exposure.

Cutaneous human papillomavirus in head and neck squamous cell carcinomas.

To evaluate the prevalence and meaning of cutaneous human papillomavirus (HPV) types in HNSCC 51 patients were analyzed for the prevalence of cutaneous as well as mucosal HPV. HPV DNA was demonstrated in 18 (35%) of 51 tumors. The majority of these HPV types belong to so-called cutaneous HPV types, whereas only HPV 6 and HPV 16 were from the mucosal HPV types. A possible role for cutaneous HPV types as co-factors in the oncogenesis of HNSCC remains to be elucidated and may be relevant for future strategies of cancer prevention.

Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves radiation tumor therapy.

PURPOSE: Investigations on the combination of radiotherapy with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) antiangiogenic agents, which has the potential to improve the clinical outcome in cancer patients. EXPERIMENTAL DESIGN: Here, we analyze the combined VEGF (SU5416) and PDGF (SU6668) receptor tyrosine kinase inhibition with irradiation in human endothelium (HUVEC), prostate cancer (PC3), and glioblastoma (U87) in vitro and in vivo. RESULTS: Combined inhibition of VEGF and PDGF signaling resulted in enhanced apoptosis, reduced cell proliferation, and clonogenic survival as well as reduced endothelial cell migration and tube formation compared with single pathway inhibition. These effects were further enhanced by additional irradiation. Likewise, in PC3 and U87 tumors growing s.c. on BALB/c nu/nu mice, dual inhibition of VEGF and PDGF signaling significantly increased tumor growth delay versus each monotherapy. Interestingly, radiation at approximately 20% of the dose necessary to induce local tumor control exerts similar tumor growth-inhibitory effects as the antiangiogenic drugs given at their maximum effective dose. Addition of radiotherapy to both mono- as well as dual-antiangiogenic treatment markedly increased tumor growth delay. With respect to tumor angiogenesis, radiation further decreased microvessel density (CD31 count) and tumor cell proliferation (Ki-67 index) in all drug-treated groups. Of note, the slowly growing PC3 tumor responded better to the antiangiogenic drug treatments than the faster-growing U87 tumor. In addition to the beneficial effect of abrogating VEGF survival signaling when combined with radiation, we identified here a novel mechanism for the tumor escape from radiation damage. We found that radiation induced up-regulation of all four isoforms of PDGF (A-D) in endothelial cells supporting adjacent smooth muscle cells resulting in a prosurvival effect of radiation. The addition of SU6668 attenuated this undesirable paracrine radiation effect, which may rationalize the combined application of radiation with PDGF signaling inhibition to increase antitumor effects. CONCLUSION: A relative low radiation dose markedly enhances local antitumor effects of combined VEGF and PDGF signaling inhibition, suggesting a promising combination regimen for local tumor treatment with radiotherapy remaining an essential element.

Differential effects of CLDR and PDR brachytherapy on cell cycle progression in a syngeneic rat prostate tumour model.

PURPOSE: The study consisted of two treatment arms comparing the effects of CLDR (continuous low dose rate) and PDR (pulsed dose rate) brachytherapy on cell cycle progression in a radioresistant rat prostate tumour model. MATERIALS AND METHODS: Interstitial PDR and CLDR brachytherapy (both 192-Ir, 0.75 Gy/h) were administered to Dunning prostate R3327-AT1 carcinomas transplanted subcutaneously into the thigh of Copenhagen rats. Increasing doses of up to 20 as well as up to 40 Gy were applied. Cell cycle distributions of the aneuploid tumour cell subpopulations were determined at 4 h (3 Gy), 24 h (18 Gy), 48 h (20 and 36 Gy), as well as during the subsequent redistribution period (20 and 40 Gy) at 72, 96, and 120 h. Tumours either implemented with an empty tubing system (n=5) or under undisturbed growth (n=5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal. RESULTS: The aneuploid cells possessed a constant DNA-Index of 1.9+/-0.06. In contrast to sham-treated controls, the aneuploid cell fraction with G2/M DNA content was significantly increased (p<0.05) after initiation of both, CLDR and PDR brachytherapy. However, CLDR resulted in an earlier accumulation of tumour cells in G2/M (24 h: 28% CLDR vs. 19% PDR, p<0.05) with a concomitant reduction of cells in G1, whereas PDR yielded delayed, but then more pronounced cell cycle changes, particularly expressed during the redistribution period after both 20 and 40 Gy. CONCLUSION: CLDR and PDR brachytherapy showed differential effects on cell cycle progression. The induction of a significantly earlier but also less persistent G2/M cell cycle arrest after CLDR compared to PDR brachytherapy implies that a substantially higher fraction of tumour cells are irradiated in G2/M after CLDR.

SU5416 and SU6668 attenuate the angiogenic effects of radiation-induced tumor cell growth factor production and amplify the direct anti-endothelial action of radiation in vitro.

In recent decades, radiation research has concentrated primarily on the cancer cell compartment. Much less is known about the effect of ionizing radiation on the endothelial cell compartment and the complex interaction between tumor cells and their microenvironment. Here we report that ionizing radiation is a potent antiangiogenic agent that inhibits endothelial cell survival, proliferation, tube formation and invasion. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor were able to reduce the radiosensitivity of endothelial cells. Yet, it is also found that radiation induces angiogenic factor production by tumor cells that can be abrogated by the addition of antiangiogenic agents. Receptor tyrosine kinase inhibitors of Flk-1/KDR/VEGFR2, FGFR1 and PDGFR beta, SU5416, and SU6668 enhanced the antiangiogenic effects of direct radiation of the endothelial cells. In a coculture system of PC3 prostate cancer cells and endothelial cells, isolated irradiation of the PC3 cells enhanced endothelial cell invasiveness through a Matrigel matrix, which was inhibited by SU5416 and SU6668. Furthermore, ionizing radiation up-regulated VEGF and basic fibroblast growth factor in PC3 cells and VEGFR2 in endothelial cells. Together these findings suggest a radiation-inducible protective role for tumor cells in the support of their associated vasculature that may be down-regulated by coadministration of angiogenesis inhibitors. These results rationalize concurrent administration of angiogenesis inhibitors and radiotherapy in cancer treatment.

Radiation-induced motility alterations in medulloblastoma cells.

Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-µm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins.

Triple combination of irradiation, chemotherapy (pemetrexed), and VEGFR inhibition (SU5416) in human endothelial and tumor cells.

PURPOSE: This is the first preclinical report evaluating a trimodal therapy consisting of irradiation, chemotherapy, and antiangiogenesis in the context of a multimodal anticancer strategy. The combination of the folate antimetabolite pemetrexed, SU5416, a receptor tyrosine kinase inhibitor of VEGFR2, and irradiation was investigated in human endothelial cells and tumor cell lines. METHODS AND MATERIALS: Primary isolated human umbilical vein endothelial cells (HUVEC), human dermal microvascular endothelial cells (HDMEC), and human glioblastoma (U87) and prostate cancer cells (PC3) were exposed to pemetrexed (2 h) alone and in combination with SU5416 (2 h). When combined with irradiation up to 8 Gy, fixed concentrations of pemetrexed (1.06 muM) and SU5416 (1.0 muM) were used. Proliferation and clonogenic assays were conducted with endothelial and tumor cells. The migration/invasion ability of endothelial cells and the ability to produce tubular structures were tested in Matrigel and tube formation assays. Apoptosis was measured by sub-G1 DNA and caspase-3 flow cytometry. To investigate underlying cell signaling, immunocytochemistry was used to detect Akt survival signaling involvement. RESULTS: Triple combination using only a low-toxicity drug exposure of pemetrexed and SU5416 results in greater response than each treatment alone or than each combination of two modalities in all tested endothelial and tumor cell models. Triple combination substantially inhibits proliferation, migration/invasion, tube formation, and clonogenic survival. Triple combination also induced the highest rate of apoptosis in HDMEC and HUVEC as indicated by sub-1 G1 and caspase-3 assessment. Interestingly, triple combination therapy also reduces proliferation and clonogenic survival significantly in U87 and PC3 tumor cell lines. SU5416 potently inhibited Akt phosphorylation which could be induced by radiation and radiochemotherapy in human endothelial cells. CONCLUSIONS: Our findings demonstrate the high antiendothelial/antitumoral efficacy of the concurrent administration of irradiation, chemotherapy, and angiogenesis inhibition in vitro. A potential explanation for the favorable combination would be that VEGF signaling inhibition downregulates Akt survival signaling upon activation by radiation and/or chemotherapy. The data also suggest that endothelial cell apoptosis may have an important role in the benefits of the presented therapy.

Dosimetry in the vicinity of a 192Ir brachytherapy line source in air.

Dose calculation in brachytherapy is based on the assumption that the radiation sources defining a matrix of dwell positions are point-like. The planning systems, however, do not sufficiently take into account the finite extension of the sources. The present study focused on the problem of dosimetry in the vicinity of a 192Ir brachytherapy line source, particularly for small source-target distances (< 1 cm). Distance-dependent dose measurements were performed using a diamond detector with high spatial resolution. The measured distributions were then compared with dose calculations based on the extended version of the Sievert's integral for line sources. The first approach utilizes the classical Sievert's formulation. The second approach takes into account the finite extension of the detector surface, resulting in improved agreement with the measured dose distribution. Finally, the effect of self-attenuation within the source is also included. This further reduces the deviation between dose calculations and measurements.

The transcriptional regulator gene E2 of the Human Papillomavirus (HPV) 16 influences the radiosensitivity of cervical keratinocytes.

BACKGROUND: Clinical studies have demonstrated that HPV induced tumors constitute a specific subclass of cancer with a better response to radiation treatment. The purpose of this study was to investigate meaning of viral E2-gene for radiosensitivity. METHODS: W12 cells contain episomal HPV 16 genomes, whereas S12 cells, which derive from the W12 line, contain HPV DNA as integrated copies. Clonogenic survival was analyzed using 96-well in vitro test. Using flow cytometry cell cycle analyses were performed. Expression of pRb and p53 were analyzed using intracellular staining. RESULTS: W12 cells (intact E2 gene) showed a lower survival fraction than S12 cells. W12 cells developed a G2/M block 24 h after irradiation with 2 Gy whereas S12 showed no G2/M bloc. After irradiation S12 cells developed polyploidy and pRb-positive cells decreased. W12 cells showed no change of pRb-positive cells. CONCLUSIONS: Depending on E2 gene status differences in cell cycle regulation might cause radioresistance. The E2/E7/pRb pathway seems to influence HPV-induced radiosensitivity. Our experiments demonstrated an effect of HPV on radiosensitivity of cervical keratinocytes via viral transcription regulator E2 pathway.

In vivo efficacy of the histone deacetylase inhibitor suberoylanilide hydroxamic acid in combination with radiotherapy in a malignant rhabdoid tumor mouse model.

PURPOSE: Histone deacetylase inhibitors are promising new substances in cancer therapy and have also been shown to sensitize different tumor cells to irradiation (XRT). We explored the effect as well as the radiosensitizing properties of suberoylanilide hydroxamic acid (SAHA) in vivo in a malignant rhabdoid tumor (MRT) mouse model. METHODS AND MATERIAL: Potential radiosensitization by SAHA was assessed in MRT xenografts by analysis of tumor growth delay, necrosis (HE), apoptosis (TUNEL), proliferation (ki-67) and γH2AX expression as well as dynamic 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG -PET) after treatment with either SAHA alone, single-dose (10 Gy) or fractionated XRT (3 × 3Gy) solely as well as in combination with SAHA compared to controls. RESULTS: SAHA only had no significant effect on tumor growth. Combination of SAHA for 8 days with single-dose XRT resulted in a higher number of complete remissions, but failed to prove a significant growth delay compared to XRT only. In contrast fractionated XRT plus SAHA for 3 weeks did induce significant tumor growth delay in MRT-xenografts. The histological examination showed a significant effect of XRT in tumor necrosis, expression of Ki-67, γH2AX and apoptosis. SAHA only had no significant effect in the histological examination. Comparison of xenografts treated with XRT and XRT plus SAHA revealed a significantly increased γH2AX expression and apoptosis induction in the mice tumors after combination treatment with single-dose as well as fractionated XRT. The combination of SAHA with XRT showed a tendency to increased necrosis and decrease of proliferation compared to XRT only, which, however, was not significant. The 18F-FDG-PET results showed no significant differences in the standard uptake value or glucose transport kinetics after either treatment. CONCLUSION: SAHA did not have a significant effect alone, but proved to enhance the effect of XRT in our MRT in vivo model.

Trimodal glioblastoma treatment consisting of concurrent radiotherapy, temozolomide, and the novel TGF-ß receptor I kinase inhibitor LY2109761.

Here we investigate the effects of the novel transforming growth factor-ß receptor I (TGF-ßRI) serine/threonine kinase inhibitor LY2109761 on glioblastoma when combined with the present clinical standard combination regimen radiotherapy and temozolomide (TMZ). Human GBM U87 (methylated MGMT promoter), T98 (unmethylated MGMT promoter), and endothelial cells (HUVECs) were treated with combinations of LY2109761, TMZ, and radiation. We found that LY2109761 reduced clonogenic survival of U87 and T98 cells and further enhanced the radiation-induced anticlonogenicity. In addition, LY2109761 had antimigratory and antiangiogenic effects in Matrigel migration and tube formation assays. In vivo, in human xenograft tumors growing subcutaneously on BALB/c nu/nu mice, LY2109761 delayed tumor growth alone and in combination with fractionated radiation and TMZ. Interestingly, as expected, the methylated U87 model was more sensitive to TMZ than the unmethylated T98 model in all experiments, whereas the opposite was found for LY2109761. Moreover, with respect to tumor angiogenesis, while LY2109761 decreased the glioblastoma proliferation index (Ki-67) and the microvessel density (CD31 count), the relative pericyte coverage (α-SMA/CD31 ratio) increased in particular after triple therapy, suggesting a vascular normalization effect induced by LY2109761. This normalization could be attributed in part to a decrease in the Ang-2/Ang-1 messenger RNA ratio. LY2109761 also reduced tumor blood perfusion as quantified by noninvasive dynamic contrast-enhanced magnetic resonance imaging. Together, the data indicate that the addition of a TGF-ßRI kinase inhibitor to the present clinical standard (radiation plus TMZ) has the potential to improve clinical outcome in human glioblastoma, especially in patients with unmethylated MGMT promoter status.

Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines.

INTRODUCTION: The pan-HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) has previously shown to be a radio-sensitizer to conventional photon radiotherapy (XRT) in pediatric sarcoma cell lines. Here, we investigate its effect on the response of two sarcoma cell lines and a normal tissue cell line to heavy ion irradiation (HIT). MATERIALS AND METHODS: Clonogenic assays after different doses of heavy ions were performed. DNA damage and repair were evaluated by measuring γH2AX via flow-cytometry. Apoptosis and cell cycle analysis were also measured via flow cytometry. Protein expression of repair proteins, p53 and p21 were measured using immunoblot analysis. Changes of nuclear architecture after treatment with SAHA and HIT were observed in one of the sarcoma cell lines via light microscopy after staining towards chromatin and γH2AX. RESULTS: Corresponding with previously reported photon data, SAHA lead to an increase of sensitivity to heavy ions along with an increase of DSB and apoptosis in the two sarcoma cell lines. In contrast, in the osteoblast cell line (hFOB 1.19), the combination of SAHA and HIT showed a significant radio-protective effect. Laser scanning microscopy revealed no significant morphologic changes after HIT compared to the combined treatment with SAHA. Immunoblot analysis revealed no significant up or down regulation of p53. However, p21 was significantly increased by SAHA and combination treatment as compared to HIT only in the two sarcoma cell lines--again in contrast to the osteoblast cell line. Changes in the repair kinetics of DSB p53-independent apoptosis with p21 involvement may be part of the underlying mechanisms for radio-sensitization by SAHA. CONCLUSION: Our in vitro data suggest an increase of the therapeutic ratio by the combination of SAHA with HIT in infantile sarcoma cell lines.

Enhancement of radiation response in osteosarcoma and rhabdomyosarcoma cell lines by histone deacetylase inhibition.

PURPOSE: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. METHODS AND MATERIALS: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. RESULTS: SAHA induced an inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). CONCLUSION: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.