Photon-induced Charge Transfer Research Articles

Mesoporous Au-CuO substrate with dual super-hydrophilicity and efficient chemical enhancement for 4-aminothiophenol SERS detection

aminothiophenol (4-ATP) residues and accumulation in aquaculture/animal husbandry are becoming a serious threat to food safety. Development of highly sensitive metal-semiconductor surface-enhanced Raman scattering (SERS) substrates for the detection of 4-ATP is urgently needed. In this work, mesoporous Au-CuO substrate with dual super-hydrophilicity and efficient chemical enhancement is constructed for high-sensitivity SERS detection of 4-ATP. Mesoporous Au-CuO substrate is prepared by thermal decomposition. The super-hydrophilic substrate could mitigate droplet-induced "coffee ring" effect, thereby promoting rapid diffusion and uniform distribution of target molecules. Meanwhile, hybridizing gold nanoparticles (Au NPs) and CuO could enhance analyte polarization rate in that multi-channel photon-induced charge transfer between the target molecule and Au-CuO substrate. Mesoporous Au-CuO exhibited high sensitivity (10−8 M) and reproducibility (Relative standard deviation (RSD=6.06 %, n=11)) for crystal violet (CV) probe. The as-prepared substrate demonstrated reliable assay ability for 4-ATP with a detection limit of 10−7 M and a good reproducibility with RSD=3.33 % (n=11). Additionally, the substrate was not impacted by heavy metal ions in actual water environment. Trace residues of 4-ATP were still detected at concentrations as low as 10−7 M. Au-CuO substrate is expected to be a favorable candidate for the detection of 4-ATP residues in complex matrices.

Optimal design and characteristic analysis of CsPbBr3 nanocrystals hybridized with 2,5-diphenyloxazole molecules for UV and X-ray detection

Scintillation is a flash of light produced in a material by the passage of a high-energy particle or photon. Desirable properties of scintillators, such as high quantum yield, low afterglow, and radiation hardness, are determined by their physical and optoelectronic properties. Metal halide perovskite (CsPbX3, X = Cl, Br, I) nanocrystals (NCs) have gained increasing attention as materials for optical and X-ray scintillators across a wide range of incident photon energies owing to their outstanding luminescent properties. In this study, we demonstrate the dependence of scintillation yield (SY) on incident photon energy ranging from ultraviolet (UV) light to X-rays in colloidal CsPbBr3 NCs hybridized with organic molecules (2,5-diphenyloxazole: PPO). The measured SY varied with the changing concentration ratio of NCs and PPO molecules. Experimental and theoretical analyses suggested that the SY is associated with the competition between photoluminescence quenching (reabsorption) and photoelectric effect enhanced by X-ray photon induced charge transfer from the organic molecules to the NCs. The optimally engineered hybrid nanomaterial scintillator exhibits excellent X-ray imaging with sharp image contrast (i.e., super-resolved edge spread function (ESF)), under X-ray irradiation commonly used for diagnosis.

Multiple valence states of Fe boosting SERS activity of Fe3O4 nanoparticles and enabling effective SERS-MRI bimodal cancer imaging

Developing novel nanoparticle-based bioprobes utilized in clinical settings with imaging resolutions ranging from cell to tissue levels is a major challenge for tumor diagnosis and treatment. Herein, an optimized strategy for designing a Fe3O4-based bioprobe for dual-modal cancer imaging based on surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI) is introduced. Excellent SERS activity of ultrasmall Fe3O4 nanoparticles (NPs) was discovered, and a 5 × 10−9 M limit of detection for crystal violet molecules was successfully obtained. The high-efficiency interfacial photon-induced charge transfer in Fe3O4 NPs was promoted by multiple electronic energy levels ascribed to the multiple valence states of Fe, which was observed using ultraviolet–visible diffuse reflectance spectroscopy. Density functional theory calculations were utilized to reveal that the narrow band gap and high electron density of states of ultrasmall Fe3O4 NPs significantly boosted the vibronic coupling resonances in the SERS system upon illumination. The subtypes of cancer cells were accurately recognized via high-resolution SERS imaging in vitro using the prepared Fe3O4-based bioprobe with high sensitivity and good specificity. Notably, Fe3O4-based bioprobes simultaneously exhibited T1-weighted MRI contrast enhancement with an active targeting capability for tumors in vivo. To the best of our knowledge, this is the first report on the use of pure semiconductor-based SERS-MRI dual-modal nanoprobes in tumor imaging in vivo and in vitro, which has been previously realized only using semiconductor–metal complex materials. The non-metallic materials with SERS–MRI dual-modal imaging established in this report are a promising cancer diagnostic platform, which not only showed excellent performance in early tumor diagnosis but also possesses great potential for image-guided tumor treatment.

Extraordinary approach to further boost plasmonic NIR-SERS by cryogenic temperature-suppressed non-radiative recombination.

We report an effective strategy to promote the near-infrared surface-enhanced Raman scattering spectroscopy (NIR-SERS) activity by boosting the photon-induced charge transfer (PICT) efficiency at cryogenic temperature. Based on as-prepared Au/Ag nano-urchins (NUs) with abundant surface defects, the extremely low temperature (77 K) can significantly weaken the metallic lattice vibration and reduce the recombination of thermal phonons and photoexcited electrons, then accelerate the migration of energetic electrons. It enables the NIR-SERS detection limit of dye molecules to be achieved at 10-17 M, which is nearly three orders of magnitude better than that at room temperature. The present work provides a new, to the best of our knowledge, approach for ultra-trace NIR-SERS bioanalysis.

Low temperature-promoted surface plasmon resonance effect and ultrasensitive surface-enhanced Raman scattering detection of creatinine

Creatinine is a key biomarker for diagnosing and monitoring kidney disease, so rapid and sensitive testing is very important. Raman spectroscopy is particularly suitable for quantitatively detecting the creatinine in the human environment because it is sensitive to subtle changes in the concentration of the analyte. In this work an effective strategy is provided to promote the activity of surface-enhanced Raman scattering spectroscopy by enhancing the photon-induced charge transfer efficiency at low temperature. The nano-gold icosahedron (Au<sub>20</sub>) is obtained by the seed-growing method, which is used as an active substrate for SERS. The ultra-low temperature (98 K) SERS detection technology is used to realize the rapid and sensitive detection of the dye molecule crystal violet (CV) and creatinine in normal saline. The experimental results show that at room temperature of 296 K, the detection limit of Au<sub>20</sub> substrate for CV molecules is as low as 10<sup>–12</sup> mol/L, and the signals are uniform; at a low temperature of 98 K, the detection limit of CV molecules can reach 10<sup>–14</sup> mol/L, which is two orders of magnitude lower than that at 296 K. As a result, the adopted cryogenic temperature can effectively weaken the lattice thermal vibration and reduce the release of phonons, then suppress phonon-assisted non-radiative recombination. So, it will increase the number of photo-induced electrons to participate in the photo-induced charge transfer efficiency. Finally, we perform the label-free detection of creatinine in saline by using an Au<sub>20</sub> substrate. The results show that the detection limit of the SERS substrate for creatinine is 10<sup>–6</sup> mol/L at 296 K, and the linear correlation coefficient of the 1619 cm<sup>–1</sup> peak is 0.9839. At a low temperature of 98 K, the detection limit of creatinine concentration is as low as 10<sup>–8</sup> mol/L, and the linear correlation coefficient of the 1619 cm<sup>–1</sup> peak becomes 0.9973. It can be seen that low temperature may further improve the detection limit of creatinine concentration and the linearity of characteristic peak. In summary, the current work provides a new idea for accurately detecting the creatinine concentration in the field of biomedicine.

Phase I Clinical Trial: Results From The Use Of 4-Demethyl-4-Cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) Plus Radiation As Treatment For Cancers Involving The CNS

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase I/II studies [AACR, #CT129, 2017] in adult subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required surgery for persistent CNS lesions following DM-CHOC-PEN therapy with 39-98.8 mg/m2 of drug. DM-CHOC-PEN was identified in samples from all 4-subjects - 90-212 ng/g tumor. Thus, the drug penetrates the CNS and tumors and is available to act as a radiosensitizer; the latter has been supported with in vitro studies [AACR, #4746, 2017]. The current presentation reviews the long-term Phase I clinical data that supports safety, dose-tolerance and use of DM-CHOC-PEN plus radiation in subjects with cancers involving the CNS – IND 68,876. DM-CHOC-PEN was administered as a 3-hr IV infusion once to subjects with advanced cancer involving the CNS. A single dose (39 mg/m2 to 98.7 mg/m2 in escalating Phase I scheme) was administered once anywhere from 48 hours to 3-weeks prior to receiving stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT). Radiation was administered in doses of 15-30 Gy depending on the size and number of lesions. Nineteen (19) subjects with cancer involving the CNS have been treated to date with DM-CHOC-PEN (6-NSCLC, 1-breast, 1-melanoma, 5-GBM, 3-sarcomas, 1-astrocytoma and 2-renal cell carcinomas). Subjects received 39, 50, 70, 86.8 or 98.7 mg/m2 of DM-CHOC-PEN. Five subjects received WBRT (30 Gy) and 14 subjects received SRS (15-24 Gy. One (1) subject with NSCLC did develop vasogenic edema and tumor necrosis which resolved and the subject is in complete remission 55+ mos. A second subject with a recurrent GBM developed Gr-3 confusion secondary to an enlarging lesion which was removed. Drug was present in ng/g of tumor conc.; confusion resolved. Ten (10) of the thirteen (13) subjects have had objective results (OS 8-58 mos.) Bioavailability for DM-CHOC-PEN revealed a rebound phenomenon @ ∼ 50 hours post-infusion with a T-release of 26.7 h. and drug in the plasma (Cmax = 17.5 μg/mL) until day 15. The AUC was linear for all doses. Pre-clinical radiosensitization in vitro studies [AACR #1917, 2017] supported the present trial. Photon induced charge transfer reactions with DM-CHOC-PEN will be discussed as a MOA. Data is presented that documents effectiveness and safety of DM-CHOC-PEN plus radiation as therapy for subjects with cancers involving the CNS. Observations during this trial supported the drug’s ability to penetrate human tumors involving the CNS and acceptability as a method to improving responses to radiation. Complete data on subject responses and observed toxicities will be presented. Supported by – NCI/SBIR grants - R43 CA213545-02 and NIH NIGMS 1 U54 GM104940 – the latter funds the Louisiana Clinical and Translational Science Center.

Hybridisation of perovskite nanocrystals with organic molecules for highly efficient liquid scintillators

Compared with solid scintillators, liquid scintillators have limited capability in dosimetry and radiography due to their relatively low light yields. Here, we report a new generation of highly efficient and low-cost liquid scintillators constructed by surface hybridisation of colloidal metal halide perovskite CsPbA3 (A: Cl, Br, I) nanocrystals (NCs) with organic molecules (2,5-diphenyloxazole). The hybrid liquid scintillators, compared to state-of-the-art CsI and Gd2O2S, demonstrate markedly highly competitive radioluminescence quantum yields under X-ray irradiation typically employed in diagnosis and treatment. Experimental and theoretical analyses suggest that the enhanced quantum yield is associated with X-ray photon-induced charge transfer from the organic molecules to the NCs. High-resolution X-ray imaging is demonstrated using a hybrid CsPbBr3 NC-based liquid scintillator. The novel X-ray scintillation mechanism in our hybrid scintillators could be extended to enhance the quantum yield of various types of scintillators, enabling low-dose radiation detection in various fields, including fundamental science and imaging.

Abstract CT101: Phase I clinical trial: results from the use of 4-demethyl-4 cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) plus radiation as treatment for cancers involving the CNS

Abstract Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase I/II studies [AACR, #CT129, 2017] in adult subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required surgery for persistent CNS lesions following DM-CHOC-PEN therapy with 39-98.8 mg/m2 of drug. DM-CHOC-PEN was identified in samples from all 4-subjects - 90-212 ng/g tumor. Thus, the drug penetrates the CNS and tumors and is available to act as a radiosensitizer; the latter has been supported with in vitro studies [AACR, #4746, 2017]. The current presentation reviews the long term Phase I clinical data that supports safety, dose-tolerance and use of DM-CHOC-PEN plus radiation in subjects with cancers involving the CNS - IND 68,876. Patients & Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once to subjects with advanced cancer involving the CNS. A single dose (39 mg/m2 to 98.7 mg/m2 in escalating Phase I scheme) was administered once anywhere from 48 hours to 3-weeks prior to receiving stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT). Radiation was administered in doses of 15-30 Gy depending on the size and number of lesions. Results: Nineteen (19) subjects with cancer involving the CNS have been treated to date with DM-CHOC-PEN (6-NSCLC, 1-breast, 1-melanoma, 5-GBM, 3-sarcomas, 1-astrocytoma & 2-renal cell carcinomas). Subjects received 39, 50, 70, 86.8 or 98.7 mg/m2 of DM-CHOC-PEN. Five subjects received WBRT (30 Gy) and 14 subjects received SRS (15-24 Gy. One (1) subject with NSCLC did develop vasogenic edema and tumor necrosis which resolved and the subject is in complete remission 55+ mos. A second subject with a recurrent GBM developed Gr-3 confusion secondary to an enlarging lesion which was removed. Drug was present in ng/g of tumor conc.; confusion resolved. Ten (10) of the thirteen (13) subjects have had objective results (OS 8-58 mos.) Bioavailability for DM-CHOC-PEN revealed a rebound phenomenon @ ~ 50 hours post-infusion with a T-release of 26.7 h. and drug in the plasma (Cmax=17.5 µg/mL) until day 15 . The AUC was linear for all doses. Pre-clinical radiosensitization in vitro studies [AACR #1917, 2017] supported the present trial. Photon induced charge transfer reactions with DM-CHOC-PEN will be discussed as a MOA. Conclusion: Data is presented that documents effectiveness and safety of DM-CHOC-PEN plus radiation as therapy for subjects with cancers involving the CNS. Observations during this trial supported the drug's ability to penetrate human tumors involving the CNS and acceptability as a method to improving responses to radiation. Complete data on subject responses and observed toxicities will be presented. Supported by - NCI/SBIR grants - R43 CA213545-02 and NIH NIGMS 1 U54 GM104940 - the latter funds the Louisiana Clinical and Translational Science Center. Citation Format: Steven J. DiBiase, Roy S. Weiner, Tallat Mahmood, Kendra Harris, Ronald Kawauchi, Kiran Devisetty, James Herman, Manish Bhandari, Marcus Ware, Paul Friedlander, Lee R. Morgan, Ali Baghian. Phase I clinical trial: results from the use of 4-demethyl-4 cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) plus radiation as treatment for cancers involving the CNS [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT101.

Organic molecular crystal-based photosynaptic devices for an artificial visual-perception system

Recreating the visual-perception properties using organic electronic devices is highly desired for visual prosthetics and artificial intelligence. Although the integration of organic light-sensing components with synaptic devices can realize the recognition and memory functions for perceived images, complicated problems in device integration for practical applications are generally encountered. Here we demonstrate a new type of organic photosynaptic device based on organic molecular crystals, which can provide optical-sensing and synaptic functions together in one device by means of a unique photon-induced charge transfer effect. This device successfully emulates the working principles of human visual perception in terms of short-term plasticity, long-term potentiation, and spike-timing-dependent plasticity. Moreover, a proof-of-concept artificial image-perception system is demonstrated by integrating the photosynapses on a flexible substrate. The new devices using organic semiconductors may open up innovative application areas, such as artificially intelligent electronic and perception systems, and facilitate the integration of such devices into next-generation flexible and stretchable electronics.

Donor-length dependent photoninduced charge transfer in two-photon absorption.

In this paper, we study the donor-length dependent photoinduced charge transfer in two-photon absorption (TPA). In the donor-acceptor (D-A) system of oligo-thiophene-fullerene, two kind of lengths of oligo-thiophene are chosen to study the donor-length dependent photoinduced charge transfer in TPA. It is found that donor length can significantly influence the rate of charge transfer. When the donor length is quarter-thiophene, the rate of charge transfer is less than 50%; while with the increase of donor-length to octant-thiophene, the rate of charge transfer can be reach up to 100%. The transition channels of photoinduced charge transfer in TPA are visualized with transition density matrix and charge difference density. Our results promote deeper understanding and rational design for donor-acceptor system with large rate of photoinduced charge transfer in TPA.

Abstract CT065: A Phase I clinical trial: Use of 4-demethyl-4-cholesteryl- oxycarbonyl-penclomedine (DM-CHOC-PEN) plus radiation as treatments for cancers involving the CNS

Abstract Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase II studies [AACR, #CT129, 2017] in subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required surgery for persistent CNS lesions following DM-CHOC-PEN therapy with 39-98.8 mg/m2 of drug. DM-CHOC-PEN was identified in samples from all 4-subjects - 90-212 ng/g tumor. Thus, the drug penetrates the CNS and tumors and is available to act as a radiosensitizer; the latter has been supported with in vitro studies [AACR, #4746, 2017]. The current presentation reviews Phase I clinical data that supports the safety, dose-tolerance and use for DM-CHOC-PEN plus radiation in subjects with cancers involving the CNS - IND 68,876. Patients & Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once to subjects with advanced cancer involving the CNS. A single dose (39 mg/m2 to 98.7 mg/m2 in escalating Phase I scheme) was administered once 3-weeks prior to receiving stereotaxic radio-surgery (SRS), gamma knife or whole brain irradiation (WBRT) therapy. Radiation was administered in doses of 15-30 Gy depending on the size and number of lesions. Results: Thirteen (13) subjects with cancer involving the CNS have been treated to date with DM-CHOC-PEN (6-NSCLC, 1-breast, 1-melanoma, 2-GBM & 3-sarcomas). Subjects received 39, 50, 70, 86.8 or 98.7 mg/m2 and 15-30 Gy of radiation. The drug/radiation combination was well tolerated. One (1) subject with NSCLC did develop vasogenic edema and tumor necrosis which resolved and the subject is in complete remission 42+ mos. A second subject with a recurrent GBM with confusion progressed - Gr-3. Ten (10) of the thirteen (13) subjects have had objective results (OS 8-54+ mos.) Bioavailability for DM-CHOC-PEN revealed a rebound phenomenon @ ~ 50 hours post-infusion with a T-release of 26.7 h. The same phenomenon was observed with RBCs (estimation using Monolix 3.2). DM-CHOC-PEN was detected bound to RBCs for 3-days (after 70 mg/m2) and was also detected in the urine (Cmax=17.5 µg/mL) until day 15. The AUC was linear for all doses. Pre-clinical radiosensitization in vitro studies [AACR #1917, 2017] support the present trial study result. Photon induced charge transfer reactions with DM-CHOC-PEN will be discussed as a MOA. Conclusion: Data is presented that documents effectiveness and safety of DM-CHOC-PEN plus radiation as therapy for subjects with cancers involving the CNS. Observations during Phase I/II clinical trials with DM-CHOC-PEN alone supported the drug’s persistent presence in human tumors after systemic administration and possible positive effects on response to subsequent radiation. Complete data on subject responses and observed toxicities will be presented. Supported by - NCI/SBIR grants - R43 CA213545-02 and NIH NIGMS 1 U54 GM104940 - the latter funds the Louisiana Clinical and Translational Science Center. Citation Format: RS Weiner, T Mahmood, Lee Roy Morgan, K. Harris, A. Baghian, SJ DiBiase, P. Friedlander, ML Ware, R. Kawauchi, J. Herman, M. Bhandari. A Phase I clinical trial: Use of 4-demethyl-4-cholesteryl- oxycarbonyl-penclomedine (DM-CHOC-PEN) plus radiation as treatments for cancers involving the CNS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT065.

Abstract CT119: Early phase I clinical trial results for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) plus radiation in cancers involving the CNS

Abstract Purpose:4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a mechanism of action (MOA) via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase I/II studies [AACR, 58, #CT129, 2017] in subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required surgery for persistent CNS lesions following DM-CHOC-PEN therapy and DM-CHOC-PEN was identified in samples from all 4-subjects - 90-212 ng/g tumor [subjects had been treated with 39-98.8 mg/m2 of drug]. Thus, the drug penetrates the CNS and concentrates in tumors. It is available, therefore, to act as a radiosensitizer as demonstrated in in vitro studies [AACR, 58, #4746, 2017]. The current presentation reviews Phase I clinical data that supports the safety, dose-tolerance, and use of DM-CHOC-PEN with radiation in subjects with cancers involving the CNS - IND 68,876. Patients & Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21 days to subjects with advanced cancer involving the CNS. A single dose was administered prior to standard radiation therapy. The dose was escalated from 39 mg/m2 to 98.7 mg/m2 I.X1, then 3-weeks later the subject received stereotaxic radio-surgery (SRS) or whole brain irradiation (WBRT). Total radiation administered was 15-30 Gy depending on the size and number of lesions. Results: Nine (9) subjects with cancer involving the CNS have been treated to date - (6-NSCLC, 1-breast, 1-melanoma & 1-sarcoma). Subjects received 39, 55, 70, 86.8 or 98.7 mg/m2 followed by 15-30 Gy of radiation. The drug/radiation combination was well tolerated. One (1) subject with NSCLC developed vasogenic edema and tumor necrosis which resolved; that subject is in complete remission 31+ mos. Six out of nine subjects have had objective responses (OS 4 - 42+ mos.) Bioavailability for DM-CHOC-PEN revealed a rebound phenomenon @ ~ 50 hours post-infusion with a T-release of 26.7 h. The same phenomenon was observed with RBCs (estimation using Monolix 3.2). DM-CHOC-PEN was detected bound to RBCs for 3-days (after 70 mg/m2); DM-CHOC-PEN was also detected in the urine (Cmax=17.5 µg/mL) until day 15. The AUC was linear for all doses. Pre-clinical in vitro studies supported the clinical data: NSCLC cells treated with DM-CHOC-PEN (0.1 -1.0 µg/mL) demonstrated 50 & 100% cytotoxicity @ 0.4 & 1.0 µg/mL. For radiation alone (6, 9 &12 Gy) - cell kill was 20 & 65% @ 6 & 12 Gy [100% kill was not observed at this dose range]; for DM-CHOC-PEN (0.25 µg/mL) plus radiation (6-12 Gy) - cell kill was 80 & 100% @ 6 & 12 Gy. Photon induced charge transfer reactions with DM-CHOC-PEN will be discussed. Conclusion: Preliminary data is presented that supports enhanced cytotoxicity and safety of DM-CHOC-PEN plus radiation as therapy for subjects with cancers involving the CNS. Observations during Phase I/II clinical trials with DM-CHOC-PEN alone support the drug's persistent presence in human tumors after systemic administration and possible positive effects on response to subsequent radiation. Complete data on subject responses and observed toxicities will be presented. Supported by - NCI/SBIR grants - R43 CA213545-01 and NIH NIGMS 1 U54 GM104940 - the latter funds the Louisiana Clinical and Translational Science Center. Citation Format: LR Morgan, T Mahmood, R S. Weiner, R Kawauchi, M Bhandari, K Devisitty, J Herman, R Summe, ML Ware, P Friedlander, AH Rodgers. Early phase I clinical trial results for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) plus radiation in cancers involving the CNS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT119.

Abstract 4746: Early clinical support for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) as a radiosensitizer in cancers involving the CNS

Abstract Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase I/II studies [AACR #CT129, 2016] in subjects with cancers involving the CNS. The current presentation reviews clinical and in vitro data that support radiosensitizing properties for DM-CHOC-PEN in cancers involving the CNS. Patients & Methods: DM-CHOC-PEN was administered as a 3-hr IV infusion once every 21 days to subjects with advanced cancer involving the CNS. The dose schedule was 2-tiered: 85.8 mg/m2 for subjects with liver involvement and 98.7 mg/m2 for subjects with normal livers. All subjects with resistant or new CNS lesions that did not respond to DM-CHOC-PEN were given the option of surgery, stereotaxic radio-surgery (SRS) or whole brain irradiation (WBRT). As preclinical support, human NSCLC adenocarcinoma cells (H-2086) growing in culture (106 cells/mL) were pretreated with DM-CHOC-PEN (0.1 -1.0 µg/mL) for 24 hrs, drug washed, re-fed fresh medium and then 48 h later irradiated (SRS with 6, 9 or 12 Gy). Results: Fifty-three (53) subjects with/without CNS involvement have been treated to date with DM-CHOC-PEN. Five (5) subjects (4-NSCLC & 1-sarcomas) in the Phase I/II trials required surgery for persistent CNS lesions following DM-CHOC-PEN therapy. DM-CHOC-PEN was identified in samples from all subjects - 90-212 ng/g tumor [subjects had been treated with 39-98.8 mg/m2 of drug]. Five subjects (1-sarcoma & 4-NSCLC) who had been treated with DM-CHOC-PEN for 6-wks - 8-mos had persistent NSCLC lesions involving the CNS were treated with SRS or WBRT. All five subjects had excellent objective results (OS 8+ - 29+ mos) with no CNS toxicity. Preclinical in vitro studies supported the clinical data: NSCLC cells treated with DM-CHOC-PEN (0.1 -1.0 µg/mL) demonstrated 50 & 100% cytotoxicity @ 0.4 & 1.0 µg/mL; for SRS alone (6, 9 &12 Gy) - cell kill was 20 & 65% @ 6 & 12 Gy [100% kill was not observed at this dose range]; for DM-CHOC-PEN (0.25 µg/mL) + SRS (6-12 Gy) - cell kill was 80 & 100% @ 6 & 12 Gy. Thus, in combination - less drug (0.25 µg/mL) and 12 Gy - produced a 100% cell kill, as compared to either SRS or drug, alone. Photon induced charge transfer reactions with DM-CHOC-PEN will be discussed. Conclusion: Preliminary data is presented that supports DM-CHOC-PEN’s cytotoxicity and radiosensitizing properties in cancers involving the CNS. Observations during clinical trials support the drug’s persistent presence in human tumors after systemic administration and notable positive effect on response to subsequent radiation. Complete data on patient responses and observed toxicities will be presented. Supported by - NCI/SBIR grants - R43/44CA132257 and NIH NIGMS 1 U54 GM104940 - the latter funds the Louisiana Clinical and Translational Science Center. Citation Format: Lee Roy Morgan, R S. Weiner, T Mahmood, R. Kawauchi, K Devisetty, J Herman, M Bhandari, R Summe, E Benes, AH Rodgers, ML Ware, JS Hayman, J Weber, Jay J. Zou. Early clinical support for 4-demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) as a radiosensitizer in cancers involving the CNS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4746. doi:10.1158/1538-7445.AM2017-4746

Ag2O/TiO2 Nanocomposite Heterostructure as a Dual Functional Semiconducting Substrate for SERS/SEIRAS Application.

Surface-enhanced Raman spectroscopy (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRAS) are complementary and powerful techniques for molecular characterization and detection. However, studies on substrates that can enhance both Raman and IR singles are extremely scanty. Here, we reported a hybrid semiconductor material (Ag2O/TiO2) coupled with a portable solid support served as a dual functional platform for both SERS and SEIRAS applications. A facile two-step deposition method was used to synthesize Ag2O/TiO2 nanocomposite on a flexible polymeric membrane without bringing any external chemical capping agent and background signal. The presence of Ag2O was proposed to enrich the photogenerated electrons onto TiO2 surface and facilitate the photon-induced charge transfer (PICT) between TiO2 and adsorbate. The heterostructure of Ag2O/TiO2 could bring additional enhancement. The enhancement factor from such hybrid semiconducting substrate was at least one or two orders of magnitude over traditional semiconducting materials and comparable to noble metals. Additionally, this substrate enabled the ultratrace detection regardless of the more Raman- or IR-active molecules and displayed distinct quantitative capacities for SERS and SEIRAS. High reproducibility of the SERS/SEIRAS spectra further confirmed the reliability and reproducibility of our substrates.

SERS Chemical Enhancement of Water Molecules from Halide Ion Coadsorption and Photoinduced Charge Transfer on Silver Electrodes

The surface-enhanced Raman scattering (SERS) signal of water is hard to be measured due to its very small Raman scattering cross section and weak adsorption on coinage metals, only electrochemical SERS spectra of water have been observed in electrode/electrolyte interfaces so far. Our present work focuses on the chemical enhancement from halide ions on SERS signals of water adsorbed on silver electrodes, by combining the metallic cluster model and hybrid density functional theory (DFT) calculations. The interfacial structures, binding interactions and the anion effect from different halides including chloride, bromide, and iodide ions have been analyzed and compared with experimental measurements in literatures. Then the excited states of halide ions modified active sites on roughened silver electrodes have been discussed. In particular, our time-dependent DFT (TD-DFT) calculations predicted that halide ions can form low-lying excited states of surface complexes, like the photon-induced charge transfer (P...

Creating and Optimizing Interfaces for Electric-Field and Photon-Induced Charge Transfer

We create and optimize a structurally well-defined electron donor-acceptor planar heterojunction interface in which electric-field and/or photon-induced charge transfer occurs. Electric-field-induced charge transfer in the dark and exciton dissociation at a pentacene/PCBM interface were probed by in situ thickness-dependent threshold voltage shift measurements in field-effect transistor devices during the formation of the interface. Electric-field-induced charge transfer at the interface in the dark is correlated with development of the pentacene accumulation layer close to PCBM, that is, including interface area, and dielectric relaxation time in PCBM. Further, we demonstrate an in situ test structure that allows probing of both exciton diffusion length and charge transport properties, crucial for optimizing optoelectronic devices. Competition between the optical absorption length and the exciton diffusion length in pentacene governs exciton dissociation at the interface. Charge transfer mechanisms in the dark and under illumination are detailed.

Photon-stimulated desorption of Na from a lunar sample: temperature-dependent effects

We report recent results in an investigation of source mechanisms for the origin of Na atoms in tenuous planetary atmospheres, focusing on non-thermal processes. Experiments include photon stimulated desorption (PSD), electron stimulated desorption (ESD), and ion sputtering of Na atoms from the surface of a lunar basalt sample. Bombardment of the sodium covered surface by 3 keV Ar + ions removes Na from the surface by sputtering into vacuum and by implantation into the sample bulk. Bombardment of the Na covered surface by ultraviolet photons or by low energy electrons ( E>3 to 4 eV) causes desorption of “hot” Na atoms. These results are consistent with our previous measurements of sodium and potassium desorption from a silica surface: electron- or photon-induced charge transfer from the substrate to the ionic adsorbate causes formation of a neutral alkali atom in a repulsive configuration, from which desorption occurs. There is a strong temperature-dependence of Na ESD and PSD signals, under conditions where the Na surface coverage is constant and thermal desorption is negligible. The yield of Na (atoms/photon) increases by 10× from 100 to 470 K; an activation energy of ∼20 meV is measured. This phenomenon may be attributed to thermally-induced changes in surface bonding sites, and will affect recent modeling of the sodium atmospheres of Mercury and the Moon.

Steady-state phonon-free current in superlattices in a strong electric field induced by terahertz radiation

The effect of strong terahertz radiation on the current-voltage characteristics in one-dimensional superlattices is studied using the method of two-time nonequilibrium Green’s functions. It is shown that the broadening of discrete spectrum lines due to elastic scattering plays a fundamental role in this problem. A new phonon-free type of photon-induced charge transfer in the hopping mode is predicted. Under certain conditions, the constant components of current and electric field may have opposite directions in this regime. The phonon-free current cannot be described in principle in the formalism of the one-time density matrix and reflects the two-time nature of correlation functions.

Photon-induced charge transfer and surface emission

Experimental measurements have been made of photon-induced charge transfer between plane-parallel electrodes. X-rays from a pulsed X-ray source were directed at near-normal incidence onto plane-parallel electrodes, and the current which flowed between the electrodes during the X-ray pulse was measured. Quantities obtained include bulk charge transfer in several dielectric materials; forward and reverse electron emission from Al, Cu, and Au surfaces; and secondary electron emission coefficients for these metals and selected dielectrics. Measured values for charge transfer and surface emission are compared with calculations.