Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Olena Taratula,1 Mehulkumar Patel,2 Canan Schumann,1 Michael A Naleway,1 Addison J Pang,1 Huixin He,2 Oleh Taratula1 1Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA; 2Department of Chemistry, Rutgers University-Newark, Newark, NJ, USA Abstract: We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy. Keywords: graphene nanosheets, phthalocyanine, photothermal therapy, photodynamic therapy, theranostic&nbsp

Mercury vapour levels in dental practices in body mercury levels of dentists and controls

Aim A study of 180 dentists in the West of Scotland was conducted to determine their exposure to mercury during the course of their work and the effects on their health and cognitive function. Design Data were obtained from questionnaires distributed to dentists and by visiting their surgeries to take measurements of environmental mercury. Methods Dentists were asked to complete a questionnaire including items on handling of amalgam, symptoms experienced, diet and possible influences on psychomotor function such as levels of stress and alcohol intake. They also completed the 12-item General Health Questionnaire. Dentists were asked to complete a dental chart of their own mouths and to give samples of urine, hair and nails for mercury analysis. The dentists were visited at their surgeries where environmental measurements were made in eight areas of the surgery and they undertook a computerised package of psychomotor tests. One hundred and eighty control subjects underwent a similar procedure, completing a questionnaire, having their amalgam surfaces counted, giving urine, hair and nail samples and undergoing the psychomotor test procedure. Results Dentists were found to have, on average, urinary mercury levels over 4 times that of control subjects although all but one dentist had urinary mercury below the Health and Safety Executive health guidance value of 20 μmol mmol−1 creatinine. Urine was found to be a better biological marker for mercury exposure than hair or nails. Dentists were significantly more likely than control subjects to have suffered from disorders of the kidney but these symptoms were not significantly associated with their level of mercury exposure as measured in urine. One hundred and twenty two (67.8%) of the 180 surgeries visited had environmental mercury measurements in one or more areas above the Occupational Exposure Standard (OES) set by the Health and Safety Executive. In the majority of these surgeries the high levels of mercury were found at the skirting and around the base of the dental chair. In 45 surgeries (25%) the personal dosimetry measurement (ie in the breathing zone of dental staff) was above the OES. Conclusion On the basis of these findings, it is recommended that greater emphasis should be made relating to safe handling of amalgam in the training and continuing professional development of dentists, that further studies are carried out on levels of mercury exposure of dental team members during the course of their working day, and that periodic health surveillance, including urinary mercury monitoring, of dental personnel should be conducted to identify possible effects of practising dentistry