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

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

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

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

Photodynamic therapy-mediated immune responses in three-dimensional tumor models

Photodynamic therapy (PDT) is a promising non-invasive phototherapeutic approach for cancer therapy that can eliminate local tumor cells and produce systemic antitumor immune responses. In recent years, significant efforts have been made in developing strategies to further investigate the immune mechanisms triggered by PDT. The majority of in vitro experimental models still rely on the two-dimensional (2D) cell cultures that do not mimic a three-dimensional (3D) cellular environment in the human body, such as cellular heterogeneity, nutrient gradient, growth mechanisms, and the interaction between cells as well as the extracellular matrix (ECM) and therapeutic resistance to anticancer treatments. In addition, in vivo animal studies are highly expensive and time consuming, which may also show physiological discrepancies between animals and humans. In this sense, there is growing interest in the utilization of 3D tumor models, since they precisely mimic different features of solid tumors. This review summarizes the characteristics and techniques for 3D tumor model generation. Furthermore, we provide an overview of innate and adaptive immune responses induced by PDT in several in vitro and in vivo tumor models. Future perspectives are highlighted for further enhancing PDT immune responses as well as ideal experimental models for antitumor immune response studies

A Monte Carlo Simulation-Based Approach to Evaluate the Performance of Three Meteorological Drought Indices in Northwest of Iran

Although meteorological drought indices are considered as important tools for drought monitoring, they are embedded with different theoretical and experimental structures. Regarding the different geographic and climatic conditions around the world, the most meteorological drought indices have been commonly applied for drought monitoring in different parts of the world. Interestingly, it is observed that such indices in the published studies on drought monitoring have usually yielded inconsistent performance. On the other hand, most studies on drought monitoring as well as the performance of drought indices has been based on short-term historical data (less than 50 years). Therefore, this study aimed to analyze and compare the performance of three common indices of SPI, RAI and PNPI to predict long-term drought events using the Monte Carlo procedure and historical data. To do this end, the 50-year recorded or historical rainfall data across 11 synoptic stations in the Northwest of Iran were employed to generate 1000 synthetic data series so that the characteristics of long-term drought might be determined and the performance of those three indices might be analyzed and compared. The results indicated a very high comparative advantage of the SPI in terms of yielding a satisfactory and detailed analysis to determine the characteristics of long-term drought. Also, the RAI indicated significant deviations from normalized natural processes. However, these results could not reasonably and sufficiently predict long-term drought. Finally, the PNPI was determined as the most uncertain and spatial index (depending on average or coefficient of variation of rainfall data) in drought monitoring