The use of laser irradiation to stimulate adipose derived stem cell proliferation and differentiation for use in autologous grafts

Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of biastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in Vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and fluences on ADSC viability and proliferation. This paper reviews the development of MSCs as potential therapeutic interventions such as autologous grafts as well as the contribution 0 f low intensity laser irradiation on the maintenance of these cells

The association between the immune system and malignancy : a brief review

The immune system has evolved to protect the host from a universe of pathogenic microbes and eliminate toxic substances from the body. It is an interactive network of lymphoid organs, cells, humoral factors, and cytokines. The essential function of the immune system in host defence is best illustrated when it goes wrong: decreased activity results in severe infections and tumours of immunodeficiency, and increased activity in allergic and autoimmune disease. Immune cells scan for the occurrence of any molecule that they consider to be foreign to the body, and transformed cells acquire antigenicity, which is recognised as non-self. A specific immune response is generated, and it results in the proliferation of antigen-specific lymphocytes. Immunity is acquired when antibodies and T-cell receptors are expressed and up-regulated through the formation and release of lymphokines, chemokines and cytokines. Both innate and acquired immune systems interact to initiate antigenic responses against carcinomas. There is an increasing body of recent evidence to support the role that the immune system plays in eliminating pre-clinical cancers. Tumour infiltration by immune cells has been shown to have powerful prognostic significance in a host of cancer types. Cytotoxic therapies, including Low Level Laser Therapy (LILI) and chemotherapy, induce potentially immunogenic cell death, releasing tumour-associated antigens in the context of a ‘danger’ signal to the immune system. An understanding of the interaction between immune cells, tumour cells and treatment modalities will therefore guide the future combination of immunotherapy with conventional therapy to achieve optimal anti-tumour effects

Podiatric interventions and phototherapy within the management of chronic diabetic foot Ulceration : a review to compare the average healing time

Abstract: Diabetic foot ulceration is a serious complication of Diabetes Mellitus and a most important risk factor for lower limb amputations. Diabetes is characterized by chronic hyperglycemia related to the resistance of target cells to the action of insulin; which leads to degenerative disorders caused by macroangiopathy, microangiopathy and neuropathy. These factors favor the occurrence of lower limb ulcers and so delay their healing. The slow healing rate of chronic diabetic foot ulceration has a negative impact on the patients’ quality of life. Thus there is a need for the development of new treatment modalities to improve healing rate and outcome of diabetic ulcerations..

Zinc phthalocyanine tetrasulfonate-loaded Ag@mSiO2 nanoparticles for active targeted photodynamic therapy of colorectal cancer

Colorectal cancer has high morbidity and mortality rate, with a high level of metastasis and recurrence due to the poor therapeutic effects. Photodynamic therapy (PDT) as an emerging clinical modality for cancer treatment provides remarkable advantages over existing treatments by generating reactive oxygen species (ROS) through light irradiating photosensitizers (PSs) in the presence of oxygen. PDT can induce immunity against recurrence and destruction of metastases. The application of nanoparticles (NPs) in targeted cancer therapy is coming to light to circumvent the limitations associated with low physiological solubility and lack of selectivity of the PS towards tumor sites. In this in vitro study, we proved the added value of NP systems on PS efficacy and a tumor-targeting ligand. Using core/shell Ag@mSiO2 NPs loaded with ZnPcS4 PS and folic acid (FA), stronger cellular localization in the human colorectal cancer cell line (Caco-2) was observed compared to the passive NC and free PS. Additionally, light-induced photodynamic activation of the ZnPcS4/Ag@mSiO2-FA nanoconjugate (NC) elicited a strong cytotoxicity effect mediated by post-PDT. The results also revealed that the active NC was able to decrease the cell viability remarkably to 38.0% ± 4.2 *** compared to the passive NC (67.0% ± 7.4*) under 0.125 µM ZnPcS4 (IC50). More importantly, the actively targeted NC-induced apoptosis where cell cycle analysis elaborated on cell death through the G0 phase, indicating the final NC’s efficacy 20 hr post-PDT treatment

Recent advances in porphyrin-based inorganic nanoparticles for cancer treatment

The application of porphyrins and their derivatives have been investigated extensively over the past years for phototherapy cancer treatment. Phototherapeutic Porphyrins have the ability to generate high levels of reactive oxygen with a low dark toxicity and these properties have made them robust photosensitizing agents. In recent years, Porphyrins have been combined with various nanomaterials in order to improve their bio-distribution. These combinations allow for nanoparticles to enhance photodynamic therapy (PDT) cancer treatment and adding additional nanotheranostics (photothermal therapy—PTT) as well as enhance photodiagnosis (PDD) to the reaction. This review examines various porphyrin-based inorganic nanoparticles developed for phototherapy nanotheranostic cancer treatment over the last three years (2017 to 2020). Furthermore, current challenges in the development and future perspectives of porphyrin-based nanomedicines for cancer treatment are also highlighted

Inorganic nanoparticles applied for active targeted photodynamic therapy of breast cancer

Photodynamic therapy (PDT) is an alternative modality to conventional cancer treatment, whereby a specific wavelength of light is applied to a targeted tumor, which has either a photosensitizer or photochemotherapeutic agent localized within it. This light activates the photosensitizer in the presence of molecular oxygen to produce phototoxic species, which in turn obliterate cancer cells. The incidence rate of breast cancer (BC) is regularly growing among women, which are currently being treated with methods, such as chemotherapy, radiotherapy, and surgery. These conventional treatment methods are invasive and often produce unwanted side effects, whereas PDT is more specific and localized method of cancer treatment. The utilization of nanoparticles in PDT has shown great advantages compared to free photosensitizers in terms of solubility, early degradation, and biodistribution, as well as far more effective intercellular penetration and uptake in targeted cancer cells. This review gives an overview of the use of inorganic nanoparticles (NPs), including: gold, magnetic, carbon-based, ceramic, and up-conversion NPs, as well as quantum dots in PDT over the last 10 years (2009 to 2019), with a particular focus on the active targeting strategies for the PDT treatment of BC

Targeted photodynamic therapy using alloyed nanoparticle-conjugated 5-aminolevulinic acid for breast cancer

Photodynamic therapy (PDT) has been investigated as an effective, non-invasive, and alternative tumor-ablative therapy that uses photosensitizers (PSs) and safe irradiation light in the presence of oxygen to generate reactive oxygen species (ROS) to kill malignant cancer cells. However, the off-target activation of the PSs can hinder effective PDT. Therefore, an advanced drug delivery system is required to selectively deliver the PS to the therapeutic region only and reduce off-target side effects in cancer treatment. The integration of laser-initiated PDT with nanotechnology has provided new opportunities in cancer therapy. In this study, plasmonic bimetallic nanoparticles (NPs) were prepared for the targeted PDT (TPDT) of in vitro cultured MCF-7 breast cancer cells. The NPs were functionalized with PEG through Au–thiol linkage to enhance their biocompatibility and subsequently attached to the PS precursor 5-aminolevulinic acid via electrostatic interactions. In order to enhance specific targeting, anti-HER-2 antibodies (Ab) were decorated onto the surface of the nanoconjugate (NC) to fabricate a 5-ALA/Au–Ag-PEG-Ab NC. In vitro studies showed that the synthesized NC can enter MCF-7 cells and localize in the cytoplasm to metabolize 5-ALA to protoporphyrin IX (PpIX). Upon light irradiation, PpIX can efficiently produce ROS for the PDT treatment of MCF-7. Cellular viability studies showed a decrease from 49.8% ± 5.6 ** to 13.8% ± 2.0 *** for free 5-ALA versus the NC, respectively, under equivalent concentrations of the PS (0.5 mM, IC50). These results suggest that the active targeted NC platform has an improved PDT effect on MCF-7 breast cancer cells

Active targeted photodynamic therapeutic effect of silver-based nanohybrids on melanoma cancer cells

Malignant melanoma is aggressive cancer that metastasizes along with the heterogeneity at the molecular and cellular levels, thereby reducing overall therapeutic efficacy. In the present research, the concept of photodynamic therapy (PDT) was investigated on silver-based nanohybrids for the treatment of A375 melanoma cancer cells. Hence, two different nanoparticles (NPs) namely Ag-PEG NPs and core/shell Ag@mSiO2 NPs were fabricated and conjugated to zinc phthalocyanine tetrasulfonate (ZnPcS4) photosensitizer (PS). Folic acid (FA) as a targeting moiety was also decorated onto the surface of nanohybrids to selectively target the folate receptors that are overexpressed on the A375 cells. Ultimately, the PDT efficacy of both ZnPcS4/Ag-PEG-FA and ZnPcS4/Ag@mSiO2-FA nanohybrids were compared via ATP viability, flow cytometry, and reactive oxygen species (ROS) assays. The obtained near-spherical shaped nanohybrids had zeta potential of -4.03 ± 0.3 mV for ZnPcS4/Ag-PEG-FA, and -14.4 ± 0.6 mV for the ZnPcS4/Ag@mSiO2-FA. A significant PDT effect was observed for the cells exposed to 674 nm laser irradiation after incubation with ZnPcS4/Ag@mSiO2-FA with ∼92%* ± 1.1 cell death compared to ∼70%* ± 2.9 cell death for ZnPcS4/Ag-PEG-FA nanohybrids owing to the higher generation of ROS for the former nanohybrids. The majority of the cell death was induced via apoptosis rather than necrosis as the nanohybrids successfully localized in mitochondria. The overall finding of this study concluded that an active targeting strategy significantly enhanced the cellular uptake of the nanohybrids compared to passive targeting. Moreover, strong surface plasmon-PS resonance coupling in ZnPcS4/Ag@mSiO2-FA nanohybrids enhanced singlet oxygen generation in comparison to the PS alone or ZnPcS4/Ag-PEG-FA nanohybrids

Susceptibility of In Vitro melanoma skin cancer to photoactivated hypericin versus aluminium(III) phthalocyanine chloride tetrasulphonate

Abstract: The sensitivity of human melanoma cells to photoactivated Hypericin (Hyp) compared to aluminium(III) phthalocyanine chloride tetrasulphonate (AlPcS4Cl) is reported in this study. Melanoma cells (A375 cell line) were treated with various concentrations of Hyp or AlPcS4Cl alone, for 1, 4, and 24 hrs; varying doses of laser irradiation alone (594 or 682 nm); or optimal concentrations of PSs combined with laser irradiation. Changes in cellmorphology, viability, membrane integrity, and proliferation after treatment of cells were determined using inverted microscopy, Trypan blue cell exclusion, Lactate Dehydrogenase (LDH) membrane integrity, and adenosine triphosphate (ATP) cell proliferation assay, respectively.More than 60%of cell survival was observed when cells were treated with 2.5 Mof Hyp or AlPcS4Cl alone at all incubation times or with 5 J/cm2 of 594 or 682 nm laser alone. Combination of PSs and respective lasers leads to a statistically significant incubation time-dependent decrease in survival of cells. Flow cytometry using the FITC Annexin V/PI apoptosis kit demonstrated that cell death induced after Hyp-PDT is via early and late apoptosis whereas early apoptosis was the main mechanism observed with AlPcS4Cl-PDT.Hyp-PDT compared to AlPcS4Cl-PDT is indicated to be a more effective cancer cell death inducer in melanoma cells

Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells

Targeted Photodynamic therapy (TPDT) is a non-invasive and site-specific treatment modality, which has been utilized to eradicate cancer tumour cells with photoactivated chemicals or photosensitizers (PSs), in the presence of laser light irradiation and molecular tissue oxygen. Breast cancer is the commonest cancer among women worldwide and is currently treated using conventional methods such as chemotherapy, radiotherapy and surgery. Despite the recent advancements made in PDT, poor water solubility and non-specificity of PSs, often affect the overall effectivity of this unconventional cancer treatment. With respect to conventional PS obstacles, great strides have been made towards the application of targeted nanoparticles in PDT to resolve these limitations. Therefore, this review provides an overview of scientific peer reviewed published studies in relation to functionalized organic nanoparticles (NPs) for effective TPDT treatment of breast cancer over the last 10 years (2009 to 2019). The main aim of this review is to highlight the importance of organic NP active based PDT targeted drug delivery systems, to improve the overall biodistribution of PSs in breast cancer tumour’s