Moustafa Ali - Academia.edu (original) (raw)

Papers by Moustafa Ali

Analytical Chemistry, 2019

Cancer Research, 2016

Plasmonic gold nanorods (AuNRs) are very promising for biomedical applications because of their s... more Plasmonic gold nanorods (AuNRs) are very promising for biomedical applications because of their strongly enhanced radiation (e.g. absorption and scattering) and non-radioactive photothermal properties due to surface plasmon resonance. In plasmonic photothermal therapy (PPTT), AuNRs absorb near infrared (NIR) laser and induce localized heat (i.e., hyperthermia) which can promote tumor tissue ablation. However, the lack of comprehensive studies to improve the efficiency of AuNRs has hindered their application. The objectives of this study were to perform a systematic analysis to optimize AuNR-PPTT based on different sizes, formulation and concentration along with various laser powers for cancer therapy in vitro and in vivo. We used AuNRs of sizes 26×6 nm and 72×19 nm with concentrations of 2.5, 5 and 10 nM, followed by 2 min of 0.5, 1, 1.78 W/cm2 NIR 808 nm diode laser exposure both in vitro and in vivo. For in vitro studies, we studied several head and neck squamous cell carcinoma (H...

The Journal of Physical Chemistry C, 2019

Plasmonic photothermal therapy (PPTT), a type of treatment involving the intravenous or intratumo... more Plasmonic photothermal therapy (PPTT), a type of treatment involving the intravenous or intratumoral injection to introduce gold nanoparticles to cancerous cells and the subsequent exposure to heatgenerating near-infrared (NIR) light, is a potentially favorable alternative to traditional treatments of localized tumors such as chemotherapy, radiotherapy, and surgery. The current main concern of PPTT, however, is the feasibility of the treatment in clinical settings. Since PPTT's initial use 15 years ago, thousands of studies have been published. In this feature article, we summarize the most recent scientific progress, including the efficacy, molecular mechanism, toxicity, and pharmacokinetics of PPTT in vitro with cancer cells and in vivo through mouse/rat model testing, animal clinical cases (such as dogs and cats), and human clinical trials. Given the benefits of PPTT, we believe that it will ultimately become a human clinical treatment that can aid in our ultimate goal of beating cancer.

Proceedings of the National Academy of Sciences of the United States of America, Jul 26, 2017

Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are... more Metastasis is responsible for most cancer-related deaths, but the current clinical treatments are not effective. Recently, gold nanoparticles (AuNPs) were discovered to inhibit cancer cell migration and prevent metastasis. Rationally designed AuNPs could greatly benefit their antimigration property, but the molecular mechanisms need to be explored. Cytoskeletons are cell structural proteins that closely relate to migration, and surface receptor integrins play critical roles in controlling the organization of cytoskeletons. Herein, we developed a strategy to inhibit cancer cell migration by targeting integrins, using Arg-Gly-Asp (RGD) peptide-functionalized gold nanorods. To enhance the effect, AuNRs were further activated with 808-nm near-infrared (NIR) light to generate heat for photothermal therapy (PPTT), where the temperature was adjusted not to affect the cell viability/proliferation. Our results demonstrate changes in cell morphology, observed as cytoskeleton protrusions-i.e.,...

Proceedings of the National Academy of Sciences of the United States of America, Apr 29, 2017

Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strateg... more Gold nanorods (AuNRs)-assisted plasmonic photothermal therapy (AuNRs-PPTT) is a promising strategy for combating cancer in which AuNRs absorb near-infrared light and convert it into heat, causing cell death mainly by apoptosis and/or necrosis. Developing a valid PPTT that induces cancer cell apoptosis and avoids necrosis in vivo and exploring its molecular mechanism of action is of great importance. Furthermore, assessment of the long-term fate of the AuNRs after treatment is critical for clinical use. We first optimized the size, surface modification [rifampicin (RF) conjugation], and concentration (2.5 nM) of AuNRs and the PPTT laser power (2 W/cm(2)) to achieve maximal induction of apoptosis. Second, we studied the potential mechanism of action of AuNRs-PPTT using quantitative proteomic analysis in mouse tumor tissues. Several death pathways were identified, mainly involving apoptosis and cell death by releasing neutrophil extracellular traps (NETs) (NETosis), which were more obv...

Journal of the American Chemical Society, Nov 30, 2016

In cancer plasmonic photothermal therapy (PPTT), plasmonic nanoparticles are used to convert ligh... more In cancer plasmonic photothermal therapy (PPTT), plasmonic nanoparticles are used to convert light into localized heat, leading to cancer cell death. Among plasmonic nanoparticles, gold nanorods (AuNRs) with specific dimensions enabling them to absorb near-infrared laser light have been widely used. The detailed mechanism of PPTT therapy, however, still remains poorly understood. Typically, surface-enhanced Raman spectroscopy (SERS) has been used to detect time-dependent changes in the intensity of the vibration frequencies of molecules that appear or disappear during different cellular processes. A complete proven assignment of the molecular identity of these vibrations and their biological importance has not yet been accomplished. Mass spectrometry (MS) is a powerful technique that is able to accurately identify molecules in chemical mixtures by observing their m/z values and fragmentation patterns. Here, we complemented the study of changes in SERS spectra with MS-based metabolom...

International journal of nanomedicine, 2016

Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at ... more Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests show...

Journal of Photochemistry and Photobiology B: Biology, 2016

Background: The photothermal properties of gold nanoparticles (GNPs) are promising therapeutic mo... more Background: The photothermal properties of gold nanoparticles (GNPs) are promising therapeutic modality for cancer. The study objective is to evaluate the therapeutic effect of the prepared PEGylated gold nano-semicubes (PEG-GNSCs) in skin cancer. The synthesized PEG-GNSCs were intermediate between cubic and rod shapes (low aspect ratio-rods). Methods: In vitro toxicity was investigated in human skin melanoma Sk-Mel-28 cells, and skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Results: The calculated IC 50 in Sk-Mel-28 cells was 3.41 μg/ml of PEG-GNSCs, in presence of laser exposure. Photothermal therapy using laser-stimulated PEG-GNSCs resulted in inhibited volume of skin tumors. Our findings indicated that the inflammatory mediators, nitric oxide and cycloxygenase-2, were inhibited in mice after being treated with low and high doses of PEG-GNSCs, accompanied with laser exposure. However, the tumor necrosis factor-α was markedly elevated, while there was no change in 5-lipoxygenase. The pro-angiogenic factor vascular endothelial growth factor was inhibited, while histone acetylation and apoptosis were induced in tumor-bearing groups, after being treated with laser-stimulated PEG-GNSCs. Conclusion: The present study indicated the promising photothermal therapeutic effect of laser-stimulated PEG-GNSCs as an effective modality to inhibit the tumor growth, the angiogenesis and partially the inflammation.

Bioconjugate Chemistry, 2016

TB remains a challenging disease to control worldwide. Nanoparticles have been used as drug carri... more TB remains a challenging disease to control worldwide. Nanoparticles have been used as drug carriers to deliver high concentrations of antibiotics directly to the site of infection, reducing the duration of treatment along with any side effects of off-target toxicities after systemic exposure to the antibiotics. Herein we have developed a drug delivery platform where gold nanorods (AuNRs) are conjugated to rifampicin (RF), which is released after the uptake into macrophage cells (RAW264.7). Due to the nature of the macrophage cells, the nanoparticles are actively internalized into macrophages and release RF after uptake, under the safety frame of the host cells (macrophage). AuNRs without RF conjugation exhibited an obvious antimicrobial activity. Therefore, the AuNRs could be a promising antimycobacterial agent and an effective delivery vehicle for the antituberculosis drug Rifampicin for use in tuberculosis therapy.

Langmuir : the ACS journal of surfaces and colloids, Jan 26, 2012

Gold nanoparticles have shown potential in photothermal cancer therapy and optoelectronic technol... more Gold nanoparticles have shown potential in photothermal cancer therapy and optoelectronic technology. In both applications, a call for small size nanorods is warranted. In the present work, a one-pot seedless synthetic technique has been developed to prepare relatively small monodisperse gold nanorods with average dimensions (length × width) of 18 × 4.5 nm, 25 × 5 nm, 15 × 4.5 nm, and 10 × 2.5 nm. In this method, the pH was found to play a crucial role in the monodispersity of the nanorods when the NaBH4 concentration of the growth solution was adjusted to control the reduction rate of the gold ions. At the optimized pH & NaBH4 concentrations, smaller gold nanorods were produced by adjusting the CTAB concentration in the growth solution. In addition, the concentration of silver ions in the growth solution was found to be pivotal in controlling the aspect ratio of the nanorods. The extinction coefficient values for the small gold nanorods synthesized with three different aspect ratio...

Cancers, 2019

For localized tumors, gold nanorod (AuNR)-assisted plasmonic photothermal therapy (PPTT) is a pot... more For localized tumors, gold nanorod (AuNR)-assisted plasmonic photothermal therapy (PPTT) is a potentially effective alternative to traditional surgery, in which AuNRs absorb near-infrared light and convert it to heat in order to kill cancer cells. However, for large tumors (volume ≥ 20 cm3), an uneven distribution of AuNRs might cause inhomogeneity of the heat distribution inside the tumor. Surgery is frequently recommended for removing large tumors, but it is associated with a high risk of cancer recurrence and metastasis. Here, we applied PPTT before surgery, which showed improved treatment for large tumors. We divided the animals (eight cats/dogs) into two groups: Group I (control), where three cases were solely treated with surgery, laser, or AuNRs alone, resulting in recurrence and metastasis; and Group II, where animals were treated with PPTT before surgery. In Group II, four out of the five cases had tumor regression without any recurrence or metastasis. Interestingly, we obs...

CYTOLOGIA, 2015

Gold nanoparticles (GNPs) shall be applied in cancer therapy, conceivably by using a simple injec... more Gold nanoparticles (GNPs) shall be applied in cancer therapy, conceivably by using a simple injection of GNPs into human veins. This will bring them in contact with red and white blood cells of the blood stream before they reach their main target, the cancer cells. However, possible cyto-and/or genotoxic effects of GNPs on lymphocytes are not known in detail and are thus studied here. Cytotoxicity was determined by Trypan blue exclusion assay. For genotoxicity, Comet and Comet-FISH (=fluorescence in situ hybridization) assays were done. In the latter test two gene markers for DNA damage, TP53 as tumor suppressor gene and TNF-α as tumor necrosis factor gene, were investigated. The cells were incubated in the presence of different concentrations of polyethylene glycol-coated rod-shaped GNPs of 50 nm or 30 nm in diameter. GNPs induced cytotoxic effects in human lymphocytes. The effects could be observed in concentration-and sizedependent manner; 30 nm sized GNPs were more toxic than 50 nm sized ones. Using the comet assay, it was demonstrated that GNPs induce high rates of DNA damage, which are represented e.g. as high ratios of tail moments, compared to non-treated lymphocytes. The target genes (TP53 and TNF-α) were observed preferentially in comet tails indicating high rates of induced DNA damage in this DNA area. Our results suggest that rod-shaped GNPs interact with human blood lymphocytes, reduce cell viability and cause relevant DNA damage in a concentration dependent manner. The small sized GNPs were more cyto-and genotoxic than big sized GNPs. The low concentration of big sized rod-shaped GNPs could be safe for cancer photothermal therapy rather than small rod GNPs. However, further investigations are recommended to be able to minimize potential risks of application.

The Journal of Physical Chemistry B, 2014

The development of new and improved photothermal contrast agents for the successful treatment of ... more The development of new and improved photothermal contrast agents for the successful treatment of cancer (or other diseases) via plasmonic photothermal therapy (PPTT) is a crucial part of the application of nanotechnology in medicine. Gold nanorods (AuNRs) have been found to be the most effective photothermal contrast agents, both in vitro and in vivo. Therefore, determining the optimum AuNR size needed for applications in PPTT is of great interest. In the present work, we utilized theoretical calculations as well as experimental techniques in vitro to determine this optimum AuNR size by comparing plasmonic properties and the efficacy as photothermal contrast agents of three different sizes of AuNRs. Our theoretical calculations showed that the contribution of absorbance to the total extinction, the electric field, and the distance at which this field extends away from the nanoparticle surface all govern the effectiveness of the amount of heat these particles generate upon NIR laser irradiation. Comparing between three different AuNRs (38 × 11, 28 × 8, and 17 × 5 nm), we determined that the 28 × 8 nm AuNR is the most effective in plasmonic photothermal heat generation. These results encouraged us to carry out in vitro experiments to compare the PPTT efficacy of the different sized AuNRs. The 28 × 8 nm AuNR was found to be the most effective photothermal contrast agent for PPTT of human oral squamous cell carcinoma. This size AuNR has the best compromise between the total amount of light absorbed and the fraction of which is converted to heat. In addition, the distance at which the electric field extends from the particle surface is most ideal for this size AuNR, as it is sufficient to allow for coupling between the fields of adjacent particles in solution (i.e., particle aggregates), resulting in effective heating in solution.