Vitamin D and Other Differentiation-promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer

The efficacy of photodynamic therapy (PDT) using aminolevulinic acid (ALA), which is preferentially taken up by cancerous cells and converted to protoporphyrin IX (PpIX), can be substantially improved by pretreating the tumor cells with vitamin D (Vit D). Vit D is one of several “differentiation-promoting agents” that can promote the preferential accumulation of PpIX within the mitochondria of neoplastic cells, making them better targets for PDT. This article provides a historical overview of how the concept of using combination agents (“neoadjuvants”) for PDT evolved, from initial discoveries about neoadjuvant effects of methotrexate and fluorouracil to later studies to determine how vitamin D and other agents actually work to augment PDT efficacy. While this review focuses mainly on skin cancer, it includes a discussion about how these concepts may be applied more broadly toward improving PDT outcomes in other types of cancer.     

Size‐dependent Tumor Response to Photodynamic Therapy and Irinotecan Monotherapies Revealed by Longitudinal Ultrasound Monitoring in an Orthotopic Pancreatic Cancer Model

Longitudinal monitoring of tumor size in vivo can provide important biological information about disease progression and treatment efficacy that is not captured by other modes of quantification. Ultrasound enables high‐throughput evaluation of orthotopic mouse models via fast acquisition of three‐dimensional tumor images and calculation of volume with a reasonable degree of accuracy. Herein, we compare orthotopic pancreatic tumor volume measurements determined by ultrasound with volume measured by calipers and tumor weight, and found strong correlations between the three modalities over a large range of tumor sizes, suggesting ultrasound can accurately quantify tumor volumes in this model. Furthermore, we demonstrate the unique ability of longitudinal treatment monitoring to reveal a tumor size‐dependent response to Benzoporphyrin Derivative photodynamic therapy (BPD‐PDT) and irinotecan. Small tumors (5–35 mm³) were found to respond well to a single round of PDT, while large tumors (35–65 mm³) showed no response to the same treatment. These results highlight the role that tumor size can play in preclinical interpretation of treatment response and more generally suggest that careful evaluation of subtle biological features such as this must be carefully considered in order to grant a more comprehensive understanding of disease biology in vivo.     

Sub-ppt level voltammetric sensor for Hg2+ detection based on nafion stabilized l-cysteine-capped Au@Ag core-shell nanoparticles

Journal of Solid State Electrochemistry - Bimetallic nanoparticles (BMNPs) have received considerable attention due to their distinctive properties when compared to the corresponding monometallic...     

Light Dosimetry for Intraperitoneal Photodynamic Therapy in a Murine Xenograft Model of Human Epithelial Ovarian Carcinoma

Few studies have been published to date measuring spatially resolved fluence rates in complex tissue geometries. Here the light distributions of three different intraperitoneal light delivery geometries in a murine ovarian cancer model were investigated to assess their influence on the tumorcidal efficacy of photodynamic therapy (PDT). In vivo fluence rate measurements in the peritoneal cavities of mice, with the light intensity being mapped in three transverse planes, were performed using fiber-optic detectors. Three different source fiber designs and placements were tested for their ability to provide uniform irradiation of the peritoneal cavity. The biological response to a PDT protocol comprising three separate treatments administered at 72 h intervals, each consisting of a 0.25 mg kg intraperitoneal injection of benzopor-phyrin derivative-mono acid ring A followed 90 min later by delivery of 15 J of 690 nm light, was measured. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass. Fluence rate measurements showed large variations in the fluence rate distribution for similar intended treatments. The most uniform and reproducible illumination was achieved using two 18 mm long cylindrical emitting optical fibers. The biological response was comparable to that produced when a flat-cleaved end optical fiber is used to illuminate the four quadrants of the abdomen sequentially. While a good reproducibility in tumor induction in this animal model exists, no correlation was found between the fluence rate distribution measured in one group of animals and the biological response in a separate group of similarly treated animals. Due to the large intra-animal variability in fluence rate distribution, representative fluence rate mapping in complex tissue geometries is of limited value when applied to an individual PDT treatment. Thus, surveillance of the fluence rate during individual treatments will be required for acceptable PDT dosimetry. To improve the versatility of this particular animal model for PDT research, a large number of extended sources are required to increase uniformity of the illumination in order to reduce unwanted cytotoxic side effects resulting from foci of high fluence rates. In this way, subsequent increase of the total energy delivered to the tumor may be possible.     

Analysis of effective molecular diffusion rates for verteporfin in subcutaneous versus orthotopic Dunning prostate tumors

Photosensitizer biodistribution change inside tissue is one of the dominant factors in photodynamic therapy efficacy. In this study, the pharmacokinetics of a benzoporphyrin derivative (BPD), delivered in verteporfin for injection formulation, have been quantified in the rat Dunning prostate tumor MAT-LyLu model, using both subcutaneous and orthotopic sites. Blood plasma sampling indicated that BPD had a bi-exponential metabolic lifetime in vivo, with the two lifetimes being 9.6 min and 8.3 h. The spatial distributions in the tumor were quantified as a function of distance from the perfused blood vessels, using fluorescence histologic images of the tumor. A fluorescent vascular marker was used to obtain locations and shapes of perfused capillaries at a wavelength of emission different from that of BPD and to allow colocalized images to be acquired of vessel and BPD locations. Using the BPD fluorescence images obtained 15 min after intravenous administration, a forward finite-element solution to the diffusion equation was used to predict the drug distribution by matching the fluorescence intensity images observed microscopically. An inverse solver was used to minimize the root mean square error between the image of simulated diffusion and the experimental image, resulting in estimation of the diffusion coefficient of BPD in the tumor models. Effective diffusion coefficients were 0.88 and 1.59 microm2/s for the subcutaneous and orthotopically grown tumors, respectively, indicating that orthotopic tumors have significantly higher vascular extravasation rates as compared with subcutaneous tumors. This analysis supports the hypothesis that leakage rates of the photosensitizer vary considerably. Thus, although varying the time between injection and optical irradiation may be used to vary the targeting between vascular and less vascular areas, the precise time of treatment will depend on the nature of the permeability of the vasculature in the tissue being treated.     

Targeting of sebocytes by aminolevulinic acid-dependent photosensitization

Photodynamic therapy using 5-aminolevulinic acid-induced protoporphyrin IX has been developed as a very useful therapeutic modality. Recently, several authors have reported on the efficacy of this procedure for acne. This approach is based on the fact that 5-aminolevulinic acid-induced protoporphyrin IX has strong selectivity for sebaceous glands. We used the immortalized human sebaceous gland cell line SZ95 to investigate cellular mechanisms of photodynamic therapy using 5-aminolevulinic acid-induced protoporphyrin IX. Quantification of induced protoporphyrin IX production showed dependence on the applied 5-aminolevulinic acid dose. When SZ95 sebocytes were differentiated by arachidonic acid treatment, there was no difference between them and the control cells with respect to both the amount of 5-aminolevulinic acid-induced protoporphyrin IX and the phototoxic effects. We altered protoporphyrin IX formation rates by growing cells scattered as single cells in the culture dishes. Single cells produced significantly lower protoporphyrin IX levels than those grown with intercellular contacts. Intracellular localization of protoporphyrin IX was imaged using confocal laser scanning microscopy. The differentiation-specific lipid droplets were virtually excluded from protoporphyrin IX fluorescence. In addition to weak mitochondrial and strong membrane fluorescence, distinctive spots with strong fluorescence were observed. These did not colocalize with fluorescent probes for mitochondria, lysosomes or the Golgi apparati.     

Existence of a Hartmann layer in the peristalsis of Sisko fluid

Analytical solutions for the peristaltic flow of a magneto hydrodynamic(MHD) Sisko fluid in a channel, under the effects of strong and weak magnetic fields, are presented. The governing nonlinear problem, for the strong magnetic field,is solved using the matched asymptotic expansion. The solution for the weak magnetic field is obtained using a regular perturbation method. The main observation is the existence of a Hartman boundary layer for the strong magnetic field at the location of the two plates of the channel. The thickness of the Hartmann boundary layer is determined analytically. The effects of a strong magnetic field and the shear thinning parameter of the Sisko fluid on the velocity profile are presented graphically.     

The role of biosensors in coronavirus disease-2019 outbreak

Herein, we have summarized and argued about biomarkers and indicators used for the detection of severe acute respiratory syndrome coronavirus 2. Antibody detection methods are not considered suitable to screen individuals at early stages and asymptomatic cases. The diagnosis of coronavirus disease 2019 using biomarkers and indicators at point-of-care level is much crucial. Therefore, it is urgently needed to develop rapid and sensitive detection methods which can target antigens. We have critically elaborated key role of biosensors to cope the outbreak situation. In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor, and surface plasmon resonance biosensors in the detection of severe acute respiratory syndrome coronavirus 2 has been underscored. Finally, we have outlined pros and cons of diagnostic approaches and future directions.