Dr. Ahmed El-Hussein M.Kamel

Cancer is among the leading causes of mortality and morbidity worldwide. Among the different types of cancers, lung cancer is the considered to be the leading cause of death related to cancer and the most commonly diagnosed form of such disease. Chemotherapy remains a dominant treatment modality for many types of cancers at different stages. However, in many cases cancer cells develop drug resistance and become non-response to chemotherapy; thus necessitating the exploration of alternative and /or complementary treatment modalities. Photodynamic Therapy (PDT) has emerged as an effective treatment modality for various malignant neoplasia and tumors. In PDT, the photochemical interaction of light, Photosensitizer (PS) and molecular oxygen produces Reactive Oxygen Species (ROS) which induces cell death. Combination therapy by using PDT and chemotherapy can promote synergistic effect against this fatal disease with the elimination of drug resistance, and enhancement the efficacy of cancer eradication. In this review, we give an overview of chemotherapeutic modalities, PDT and the different types of drugs associated with each therapy. Furthermore, we also explored the combined use of chemotherapy and PDT in the course of lung cancer treatment and how this approach could be the last resort for thousands of patients that have been diagnosed by this fatal disease.

Viral infections pose significant health challenges globally by affecting millions of people worldwide and consequently resulting in a negative impact on both socioeconomic development and health. Corona virus disease 2019 (COVID-19) is a clear example of how a virus can have a global impact in the society and has demonstrated the limitations of detection and diagnostic capabilities globally. Another virus which has posed serious threats to world health is the human immunodeficiency virus (HIV) which is a lentivirus of the retroviridae family responsible for causing acquired immunodeficiency syndrome (AIDS). Even though there has been a significant progress in the HIV biosensing over the past years, there is still a great need for the development of point of care (POC) biosensors that are affordable, robust, portable, easy to use and sensitive enough to provide accurate results to enable clinical decision making. The aim of this study was to present a proof of concept for detecting HIV-1 pseudoviruses by using anti-HIV1 gp41 antibodies as capturing antibodies. In our study, glass substrates were treated with a uniform layer of silane in order to immobilize HIV gp41 antibodies on their surfaces. Thereafter, the HIV pseudovirus was added to the treated substrates followed by addition of anti-HIV gp41 antibodies conjugated to selenium nanoparticle (SeNPs) and gold nanoclusters (AuNCs). The conjugation of SeNPs and AuNCs to anti-HIV gp41 antibodies was characterized using UV-vis spectroscopy, transmission electron microscopy (TEM) and zeta potential while the surface morphology was characterized by fluorescence microscopy, atomic force microscopy (AFM) and Raman spectroscopy. The UV-vis and zeta potential results showed that there was successful conjugation of SeNPs and AuNCs to anti-HIV gp41 antibodies and fluorescence microscopy showed that antibodies immobilized on glass substrates were able to capture intact HIV pseudoviruses. Furthermore, AFM also confirmed the capturing HIV pseudoviruses and we were able to differentiate between substrates with and without the HIV pseudoviruses. Raman spectroscopy confirmed the presence of biomolecules related to HIV and therefore this system has potential in HIV biosensing applications.

The current research focuses on the effect of variable doses of red laser on the chick embryonic development. He-Ne laser of 632-nm wavelength was used as an irradiation source in the first 48 h post-laying of chicken eggs. We have used five different doses: 2, 1, 0.3, 0.2, and 0.1 mJ/cm that needed a time range for about 400-20 s. Those irradiated embryos were left for additional 11 days for incubation in normal conditions, where they are blindly studied after the 11 day. Light microscopy was used in this study to investigate the histological and pathological features of the different experimental groups compared to the control one. However, electron microcopy was utilized to trace the apoptotic distribution in the developmental embryos. Minor abnormalities that are dependent on the laser dose have been shown in the irradiated embryos when compared to the sham group, where the highest laser dose showed about 12% embryonic development anomalies when related to the other irradiated groups. Irradiated embryos were found to express more INF-γ and IL-2 as circulating cytokines relative to the unexposed group, where the levels of IL-2 were highly significantly increased by all laser doses (0.3 mJ/cm light dose recipient group showed significant increase only when compared to the control group). IFN-γ levels were significantly increased as well by light doses above 0.2 mJ/cm. This IFN-γ increase trend seemed to be laser dose-dependent. Simultaneously, these combined results propose the ability of high laser doses in inducing incurable changes in the embryonic development and consequently such alterations can have potential therapeutic applications through what is known as photobiomodulation.

We recently reported that addition of the non-toxic salt, potassium iodide can potentiate antimicrobial photodynamic inactivation of a broad-spectrum of microorganisms, producing many extra logs of killing. If the photosensitizer (PS) can bind to the microbial cells, then delivering light in the presence of KI produces short-lived reactive iodine species, while if the cells are added after light the killing is caused by molecular iodine produced as a result of singlet oxygen-mediated oxidation of iodide. In an attempt to show the importance of PS-bacterial binding, we compared two charged porphyrins, TPPS4 (thought to be anionic and not able to bind to Gram-negative bacteria) and TMPyP4 (considered cationic and well able to bind to bacteria). As expected TPPS4+light did not kill Gram-negative Escherichia coli, but surprisingly when 100mM KI was added, it was highly effective (eradication at 200nM+10J/cmof 415nm light). TPPS4 was more effective than TMPyP4 in eradicating the Gram-positive bacteria, methicillin-resistant Staphylococcus aureus and the fungal yeast Candida albicans (regardless of KI). TPPS4 was also highly active against E. coli after a centrifugation step when KI was added, suggesting that the supposedly anionic porphyrin bound to bacteria and Candida. This was confirmed by uptake experiments. We compared the phthalocyanine tetrasulfonate derivative (ClAlPCS4), which did not bind to bacteria or allow KI-mediated killing of E. coli after a spin, suggesting it was truly anionic. We conclude that TPPS4 behaves as if it has some cationic character in the presence of bacteria, which may be related to its delivery from suppliers in the form of a dihydrochloride salt.

Rose Bengal (RB) is a halogenated xanthene dye that has been used to mediate antimicrobial photodynamic inactivation for several years. While highly active against Gram-positive bacteria, RB is largely inactive in killing Gram-negative bacteria. We have discovered that addition of the non-toxic salt potassium iodide (100mM) potentiates green light (540nm)-mediated killing by up to six extra logs with Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive methicillin resistant Staphylococcus aureus, and fungal yeast Candida albicans. The mechanism is proposed to be singlet oxygen addition to iodide anion to form peroxyiodide, which decomposes into radicals, and finally forms hydrogen peroxide and molecular iodine. The effects of these different bactericidal species can be teased apart by comparing killing in three different scenarios: (1) cells+RB+KI are mixed together then illuminated with green light; (2) cells+RB are centrifuged then KI added then green light; (3) RB+KI+green light then cells added after light. We also showed that KI could potentiate RB-PDT in a mouse model of skin abrasions infected with bioluminescent P. aeruginosa.

BACKGROUND: Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of potent antibiotics puts us at a disadvantage in the fight against infectious diseases, especially those caused by antibiotic-resistant microbial strains. To this end, an urgent need to search for alternative antimicrobial approaches has arisen. In the last decade, light-based therapy has made significant strides in this fight to combat antibiotic resistance among various microbial strains. This method includes utilizing antimicrobial blue light, antimicrobial photodynamic therapy, and germicidal ultraviolet irradiation, among others. Light-based therapy is advantageous over traditional antibiotic-based therapy in that it selectively eradicates microbial cells without harming human cells and tissues.

METHODS: This review highlights the patents on light-based therapy that were filed approximately within the last decade and are dedicated to eradicating pathogenic microbes.

RESULTS: The treatments and devices discussed in this review are interestingly enough to be used in various different functions and settings, such as dental applications, certain diseases in the eye, skin and hard surface cleansing, decontamination of internal organs (e.g., the stomach), decontamination of apparel and equipment, eradication of pathogenic microbes from buildings and rooms, etc. Most of the devices and inventions introduce methods of destroying pathogenic bacteria and fungi without harming human cells.

CONCLUSIONS: Light-based antimicrobial approaches hold great promise for the future in regards to treating antibiotic-resistant infections and diseases.

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