Photobiomodulation: a novel approach to promote trans-differentiation of adipose-derived stem cells into neuronal-like cells.

JOURNAL/nrgr/04.03/01300535-202502000-00035/figure1/v/2024-05-28T214302Z/r/image-tiff Photobiomodulation, originally used red and near-infrared lasers, can alter cellular metabolism. It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation, near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration, which is necessary for the cells homing to the site of injury. In this in vitro study, we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries. We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2. As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects. Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers, with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group. Interestingly, green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation, while near-infrared photobiomodulation notably increased the expression of neuronal markers. Through biochemical analysis and enzyme-linked immunosorbent assays, we observed marked improvements in viability, proliferation, membrane permeability, and mitochondrial membrane potential, as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor. Overall, our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells, offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.

Expected role of photodynamic therapy to relieve skin damage in nuclear or radiological emergency: Review.

Nuclear and radiological accidents can occur due to poor management, in transportation, radiation therapy and nuclear wards in hospitals, leading to extreme radiation exposure and serious consequences for human health. Additionally, in many of previous radiological accidents, skin damage was observed in patients and survivors due to the high radiation exposure. However, as part of a medical countermeasures in a nuclear/radiological emergency, it is critical to plan for the treatment of radiation-induced skin damage. Hence, the new, non-invasive technology of photodynamic therapy (PDT) is projected to be more effectively used for treating skin damage caused by high-dose radiation. PDT plays an important role in treating, repairing skin damage and promoting wound healing as evidenced by research. This review, highlighted and recommended potential impacts of PDT to repair and decrease radiation-induced skin tissue damage. Moreover, we have suggested some photosensitizer (PS) agent as radio-mitigator drugs to decrease radiobiological effects.

Enhancing Osteoblast Differentiation from Adipose-Derived Stem Cells Using Hydrogels and Photobiomodulation: Overcoming In Vitro Limitations for Osteoporosis Treatment.

Osteoporosis represents a widespread and debilitating chronic bone condition that is increasingly prevalent globally. Its hallmark features include reduced bone density and heightened fragility, which significantly elevate the risk of fractures due to the decreased presence of mature osteoblasts. The limitations of current pharmaceutical therapies, often accompanied by severe side effects, have spurred researchers to seek alternative strategies. Adipose-derived stem cells (ADSCs) hold considerable promise for tissue repair, albeit they encounter obstacles such as replicative senescence in laboratory conditions. In comparison, employing ADSCs within three-dimensional (3D) environments provides an innovative solution, replicating the natural extracellular matrix environment while offering a controlled and cost-effective in vitro platform. Moreover, the utilization of photobiomodulation (PBM) has emerged as a method to enhance ADSC differentiation and proliferation potential by instigating cellular stimulation and facilitating beneficial performance modifications. This literature review critically examines the shortcomings of current osteoporosis treatments and investigates the potential synergies between 3D cell culture and PBM in augmenting ADSC differentiation towards osteogenic lineages. The primary objective of this study is to assess the efficacy of combined 3D environments and PBM in enhancing ADSC performance for osteoporosis management. This research is notably distinguished by its thorough scrutiny of the existing literature, synthesis of recent advancements, identification of future research trajectories, and utilization of databases such as PubMed, Scopus, Web of Science, and Google Scholar for this literature review. Furthermore, the exploration of biomechanical and biophysical stimuli holds promise for refining treatment strategies. The future outlook suggests that integrating PBM with ADSCs housed within 3D environments holds considerable potential for advancing bone regeneration efforts. Importantly, this review aspires to catalyse further advancements in combined therapeutic strategies for osteoporosis regeneration.

The Application of Photobiomodulation on Mesenchymal Stem Cells and its Potential Use for Tenocyte Differentiation.

Tendinopathy is a prevalent and debilitating musculoskeletal disorder. Uncertainty remains regarding its pathophysiology, but it is believed to be a combination of inflammation, damage, degenerative changes, and unsuccessful repair mechanisms. Cell-based therapy is an emerging regenerative medicine modality that uses mesenchymal stem cells (MSCs), their progeny or exosomes to promote tendon healing and regeneration. It is based on the fact that MSCs can be differentiated into tenocytes, the major cell type within tendons, and facilitate tendon repair. Photobiomodulation (PBM) is a non-invasive and potentially promising therapeutic technique that utilizes low-level light to alter intracellular processes and promote tissue healing and regeneration. Recent studies have examined the potential for PBM to improve MSC therapy use in tendinopathy by promoting viability, proliferation, and differentiation. As well as enhance tendon regeneration. This review focuses on Photobiomodulation and MSC therapy applications in regenerative medicine and their potential for tendon tissue engineering.

The phototoxic effect of a gold-antibody-based nanocarrier of phthalocyanine on melanoma monolayers and tumour spheroids.

In recent years, photodynamic therapy (PDT) has garnered significant attention in cancer treatment due to its increased potency and non-invasiveness compared to conventional therapies. Active-targeted delivery of photosensitizers (PSs) is a mainstay strategy to significantly reduce its off-target toxicity and enhance its phototoxic efficacy. The anti-melanoma inhibitory activity (MIA) antibody is a targeting biomolecule that can be integrated into a nanocarrier system to actively target melanoma cells due to its specific binding to MIA antigens that are highly expressed on the surface of melanoma cells. Gold nanoparticles (AuNPs) are excellent nanocarriers due to their ability to encapsulate a variety of therapeutics, such as PSs, and their ability to bind with targeting moieties for improved bioavailability in cancer cells. Hence, we designed a nanobioconjugate (NBC) composed of zinc phthalocyanine tetrasulfonic acid (ZnPcS4), AuNPs and anti-MIA Ab to improve ZnPcS4 bioavailability and phototoxicity in two and three-dimensional tumour models. In summary, we demonstrated that this nanobioconjugate showed significant inhibitory effects on both melanoma models due to increased ROS yields and bioavailability of the melanoma cells compared to free ZnPcS4.

Green synthesis and characterization of AgNPs, liposomal loaded AgNPs and ZnPcS4 photosensitizer for enhanced photodynamic therapy effects in MCF-7 breast cancer cells.

Breast cancer remains a formidable challenge in oncology despite significant advancements in treatment modalities. Conventional therapies such as surgery, chemotherapy, radiation therapy, and hormonal therapy have been the mainstay in managing breast cancer for decades. However, a subset of patient's experiences treatment failure, leading to disease recurrence and progression. Therefore, this study investigates the therapeutic potential of green-synthesized silver nanoparticles (AgNPs) using an African medicinal plant (Dicoma anomala methanol root extract) as a reducing agent for combating breast cancer. AgNPs were synthesized using the bottom-up approach and later modified with liposomes (Lip) loaded with photosensitizer (PS) zinc phthalocyanine tetrasulfonate (Lip@ZnPcS4) using thin film hydration method. The successful formation and Lip modification of AgNPs, alongside ZnPcS4, were confirmed through various analytical techniques including UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Following a 24 h treatment period, MCF-7 cells were assessed for viability using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT viability assay), cell death analysis using mitochondrial membrane potential (MMP) (ΔΨm), Annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) kit, and caspase- 3, 8 and 9 activities. The experiments were repeated four times (n = 4), and the results were analyzed using SPSS statistical software version 27, with a confidence interval set at 0.95. The synthesized nanoparticles and nanocomplex, including AgNPs, AgNPs-Lip, Lip@ZnPcS4, and AgNPs-Lip@ZnPcS4, exhibited notable cytotoxicity and therapeutic efficacy against MCF-7 breast cancer cells. Notably, the induction of apoptosis, governed by the upregulation of apoptotic proteins i.e., caspase 8 and 9 activities. In addition, caspase 3 was not expressed by MCF-7 cells in both control and experimental groups. Given the challenging prognosis associated with breast cancer, the findings underscore the promise of liposomal nanoformulations in cancer photodynamic therapy (PDT), thus warranting further exploration in clinical settings.

Apoptotic efficiency of Dicoma anomala biosynthesized silver nanoparticles against A549 lung cancer cells.

Lung cancer is one of the common forms of cancer that affects both men and women and is regarded as the leading cause of cancer related deaths. It is characterized by unregulated cell division of altered cells within the lung tissues. Green nanotechnology is a promising therapeutic option that is adopted in cancer research. Dicoma anomala (D. anomala) is one of the commonly used African medicinal plant in the treatment of different medical conditions including cancer. In the present study, silver nanoparticles (AgNPs) were synthesized using D. anomala MeOH root extract. We evaluated the anticancer efficacy of the synthesized AgNPs as an individual treatment as well as in combination with pheophorbide a (PPBa) mediated photodynamic therapy (PDT) in vitro. UV-VIS spectroscopy, high-resolution transmission electron microscopy (HR-TEM), Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) was used to confirm the formation of D.A AgNPs. Post 24 h treatment, A549 cells were evaluated for ATP proliferation, morphological changes supported by LIVE/DEAD assay, and caspase activities. All experiments were repeated four times (n=4), with findings being analysed using SPSS statistical software version 27 set at 0.95 confidence interval. The results from the present study revealed a dose-dependent decrease in cell proliferation in both individual and combination therapy of PPBa mediated PDT and D.A AgNPs on A549 lung cancer cells with significant morphological changes. Additionally, LIVE/DEAD assay displayed a significant increase in the number of dead cell population in individual treatments (i.e., IC50's treated A549 cells) as well as in combination therapy. In conclusion, the findings from this study demonstrated the anticancer efficacy of green synthesized AgNPs as a mono-therapeutic drug as well as in combination with a chlorophyll derivative PPBa in PDT. Taken together, the findings highlight the therapeutic potential of green nanotechnology in medicine.

Targeted photodynamic therapy technique of Janus nanoparticles on breast cancer.

Spherical gold/polyacrylic acid (Au/PAA) polymer-inorganic Janus nanoparticles (JNPs) with simultaneous therapeutic and targeting functions were fabricated. The obtained Au/PAA JNPs were further selectively functionalized with folic acid (FA) and thiol PEG amine (SH-PEG-NH2) on Au sides to provide superior biocompatibility and active targeting, while the other PAA sides were loaded with 5-aminolevulinic acid (5-ALA) to serve as a photosensitizer (PS) for photodynamic therapeutic (PDT) effects on MCF-7 cancer cells. The PS loading of 5-ALA was found to be 83% with an average hydrodynamic size and z-potential of 146 ± 0.8 nm and -6.40 mV respectively for FA-Au/PAA-ALA JNPs. The in vitro PDT study of the JNPs on MCF-7 breast cancer cells under 636 nm laser irradiation indicated the cell viability of 24.7% ± 0.5 for FA-Au/PAA-ALA JNPs at the IC50 value of 0.125 mM. In this regard, the actively targeted FA-Au/PAA-ALA JNPs treatment holds great potential for tumour therapy with high cancer cell-killing efficacy.

Actively targeted photodynamic therapy in multicellular colorectal cancer spheroids via functionalised gold nanoparticles.

Photodynamic therapy (PDT) holds great potential to overcome limitations associated with common colorectal cancer (CRC) treatment approaches. Targeted photosensitiser (PS) delivery systems using nanoparticles (NPs) with targeting moieties are continually being designed, which are aimed at enhancing PS efficacy in CRC PDT. However, the optimisation of targeted PS delivery systems in most, in vitro PDT studies has been conducted on two dimensional (2D) monolayers cell cultures. In our present study, we developed a nano PS delivery system for in vitro cultured human colorectal three-dimensional multicellular spheroids (3D MCTS). PEGylated gold nanoparticles (PEG-AuNPs) were prepared and attached to ZnPcS4PS and further functionalised with specific CRC targeting anti-Guanylate Cyclase monoclonal antibodies(mAb). The ZnPcS4-AuNP-Anti-GCC Ab (BNC) nanoconjugates were successfully synthesised and their photodynamic effect investigated following exposure to laser irradiation and demonstrated enhanced anticancer effects in Caco-2 cells cultivated as 3D MCTS spheroids. Our findings suggest that targeted BNC nanoconjugates can improve the efficacy of PDT and highlight the potential of 3D MCTS tumour model for evaluating of targeted PDT.

Targeting Wnt/ß-catenin signaling and its interplay with TGF-ß and Notch signaling pathways for the treatment of chronic wounds.

Wound healing is a tightly regulated process that ensures tissue repair and normal function following injury. It is modulated by activation of pathways such as the transforming growth factor-beta (TGF-ß), Notch, and Wnt/ß-catenin signaling pathways. Dysregulation of this process causes poor wound healing, which leads to tissue fibrosis and ulcerative wounds. The Wnt/ß-catenin pathway is involved in all phases of wound healing, primarily in the proliferative phase for formation of granulation tissue. This review focuses on the role of the Wnt/ß-catenin signaling pathway in wound healing, and its transcriptional regulation of target genes. The crosstalk between Wnt/ß-catenin, Notch, and the TGF-ß signaling pathways, as well as the deregulation of Wnt/ß-catenin signaling in chronic wounds are also considered, with a special focus on diabetic ulcers. Lastly, we discuss current and prospective therapies for chronic wounds, with a primary focus on strategies that target the Wnt/ß-catenin signaling pathway such as photobiomodulation for healing diabetic ulcers.

Three-Dimensional Cell Culture of Adipose-Derived Stem Cells in a Hydrogel with Photobiomodulation Augmentation.

Adipose-derived stem cells (ADSCs), possessing multipotent mesenchymal characteristics akin to stem cells, are frequently employed in regenerative medicine due to their capacity for a diverse range of cell differentiation and their ability to enhance migration, proliferation, and mitigate inflammation. However, ADSCs often face challenges in survival and engraftment within wounds, primarily due to unfavorable inflammatory conditions. To address this issue, hydrogels have been developed to sustain ADSC viability in wounds and expedite the wound healing process. Here, we aimed to assess the synergistic impact of photobiomodulation (PBM) on ADSC proliferation and cytotoxicity within a 3D cell culture framework. Immortalized ADSCs were seeded into 10 µL hydrogels at a density of 2.5 x 103 cells and subjected to irradiation using 525 nm and 825 nm diodes at fluencies of 5 J/cm2 and 10 J/cm2. Morphological changes, cytotoxicity, and proliferation were evaluated at 24 h and 10 days post-PBM exposure. The ADSCs exhibited a rounded morphology and were dispersed throughout the gel as individual cells or spheroid aggregates. Importantly, both PBM and 3D culture framework displayed no cytotoxic effects on the cells, while PBM significantly enhanced the proliferation rates of ADSCs. In conclusion, this study demonstrates the use of hydrogel as a suitable 3D environment for ADSC culture and introduces PBM as a significant augmentation strategy, particularly addressing the slow proliferation rates associated with 3D cell culture.

Anticancer photodynamic activities of triphenylphosphine-labelled phthalocyanines and their bovine serum albumin-gold nanoparticles- complexes on melanoma A375 cell lines in vitro.

This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (1O2) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.

Overcoming challenges in cancer treatment: Nano-enabled photodynamic therapy as a viable solution.

Cancer presents a formidable challenge, necessitating innovative therapies that maximize effectiveness while minimizing harm to healthy tissues. Nanotechnology has emerged as a transformative force in cancer treatment, particularly through nano-enabled photodynamic therapy (NE-PDT), which leverages precise and targeted interventions. NE-PDT capitalizes on photosensitizers activated by light to generate reactive oxygen species (ROS) that initiate apoptotic pathways in cancer cells. Nanoparticle enhancements optimize this process, improving drug delivery, selectivity, and ROS production within tumors. This review dissects NE-PDT's mechanistic framework, showcasing its potential to harness apoptosis as a potent tool in cancer therapy. Furthermore, the review explores the synergy between NE-PDT and complementary treatments like chemotherapy, immunotherapy, and targeted therapies, highlighting the potential to amplify apoptotic responses, enhance immune recognition of cancer cells, and inhibit resistance mechanisms. Preclinical and clinical advancements in NE-PDT demonstrate its efficacy across various cancer types. Challenges in translating NE-PDT into clinical practice are also addressed, emphasizing the need for optimizing nanoparticle design, refining dosimetry, and ensuring long-term safety. Ultimately, NE-PDT represents a promising approach in cancer therapy, utilizing the intricate mechanisms of apoptosis to address therapeutic hurdles. The review underscores the importance of understanding the interplay between nanoparticles, ROS generation, and apoptotic pathways, contributing to a deeper comprehension of cancer biology and novel therapeutic strategies. As interdisciplinary collaborations continue to thrive, NE-PDT offers hope for effective and targeted cancer interventions, where apoptosis manipulation becomes central to conquering cancer. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Green nanotech paradigm for enhancing sesquiterpene lactone therapeutics in cancer.

In the field of cancer therapy, sesquiterpene lactones (SLs) derived from diverse Dicoma species demonstrate noteworthy bioactivity. However, the translation of their full therapeutic potential into clinical applications encounters significant challenges, primarily related to solubility, bioavailability, and precise drug targeting. Despite these obstacles, our comprehensive review introduces an innovative paradigm shift that integrates the inherent therapeutic properties of SLs with the principles of green nanotechnology. To overcome issues of solubility, bioavailability, and targeted drug delivery, eco-friendly strategies are proposed for synthesizing nanocarriers. Green nanotechnology has emerged as a focal point in addressing environmental and health concerns linked to conventional treatments. This progressive approach of green nanotechnology holds promise for the development of safe and sustainable nanomaterials, particularly in the field of drug delivery. This groundbreaking methodology signifies a pioneering advancement in the creation of novel and effective anticancer therapeutics. It holds substantial potential for transforming cancer treatment and advancing the landscape of natural product research.

Multifunctional embelin- poly (3-hydroxybutyric acid) and sodium alginate-based core-shell electrospun nanofibrous mat for wound healing applications.

In this study, coaxial electrospinning is employed to make core-shell fibers, which represents a major advance in biomaterial innovation. Fibers that combine a protective shell and a therapeutic agent-loaded core, herald a revolutionary era in tissue engineering and wound care. Besides supporting cell growth, these fibers also preserve sterility, which makes them ideal for advanced wound dressings. We used embelin as the basis for this study because of its natural antibacterial properties. Its effectiveness in inhibiting the growth of bacteria made it the ideal candidate for our research. We have synthesized core-shell nanofibers that contain Sodium Alginate (SAL) in a Poly (ethylene oxide) (PEO) shell and Embelin in a Poly (3-hydroxybutyric acid) (PHB) core, which exhibit the homogeneity and flawless structure required for biomedical applications. When using SAL-PEO and EMB-PHB solutions dissolved in 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP), high consistency in results can be achieved. A biocompatibility study was conducted using NIH-3T3 fibroblasts, which demonstrated remarkable adhesion and proliferation, with over 95 % growth supporting both PHB + SAL-PEO and EMB-PHB + SAL-PEO fibers. In addition, the scaffold loaded with Embelin shows strong antibacterial activity and cytocompatibility. The combined activity demonstrates the potential of EMB-PHB + SAL-PEO fibers in wound healing, where tissue regeneration and preservation of sterility are crucial. The optimized concentration of Embelin within these scaffolds demonstrates robust antibacterial efficacy while exhibiting minimal toxicity, thus positioning them as highly promising candidates for a wide range of biological applications, including wound healing.

Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer.

Cancer remains one of the diseases with the highest incidence and mortality globally. Conventional treatment modalities have demonstrated threatening drawbacks including invasiveness, non-controllability, and development of resistance for some, including chemotherapy, radiation, and surgery. Sono-photodynamic combinatorial therapy (SPDT) has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic approach. SPDT combines the mechanism of action of sonodynamic therapy (SDT), which uses ultrasound, and photodynamic therapy (PDT), which uses light, to activate a sensitizer and initiate cancer eradication. The use of phthalocyanines (Pcs) as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and PDT. This review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.

Phthalocyanine-based probes in alleviating or evading tumour-hypoxia for enhanced photo- and/ sono-mediated therapeutic efficacies.

This review discusses the possible methods for improving therapeutic efficacies of phthalocyanine (Pcs) -based therapeutic probes in photo- and sono-dynamic therapies under hypoxic conditions. Herein, the structural design strategies including varying the central metal, position substituents and the effects of adjuvant used in supplementing the therapeutics activities of Pcs or formation of NPs are discussed for cancer therapies in hypoxic conditions. Different mechanisms induced for cell death influenced by the compositions of the Pcs-probes are discussed. The focus mainly highlights the oxygen (O2) -dependent mechanisms including methods of supplementing tumour microenvironment O2-concentrations to promote PDT or SDT therapies. Alternatively, O2-independent mechanisms mainly used to evade hypoxia by stimulating anticancer processes that don't require O2 to initiate cell death, such as the Fenton reaction or thermal ablation effects.

Aluminium phthalocyanine-mediated photodynamic therapy induces ATM-related DNA damage response and apoptosis in human oesophageal cancer cells.

Introduction: Photodynamic therapy (PDT) is a light-based technique used in the treatment of malignant and non-malignant tissue. Aluminium-phthalocyanine chloride tetra sulfonate (AlPcS4Cl)-mediated PDT has been well investigated on several cancer types, including oesophageal cancer. However, the effects of (AlPcS4Cl)-mediated PDT on DNA damage response and the mechanism of cell death in oesophageal cancer needs further investigation. Methods: Here, we examined the in vitro effects of AlPcS4Cl-mediated PDT on cell cycle, DNA damage response, oxidative stress, and intrinsic apoptotic cell death pathway in HKESC-1 oesophageal cancer cells. The HKESC-1 cells were exposed to PDT using a semiconductor laser diode (673.2 nm, 5 J/cm2 fluency). Cell viability and cytotoxicity were determined by the ATP cell viability assay and the lactate dehydrogenase (LDH) release assay, respectively. Cell cycle and DNA damage response (DDR) analyses were conducted using the Muse™ cell cycle kit and the Muse® multi-color DNA damage kit, respectively. The mode of cell death was identified using the Annexin V-FITC/PI detection assay and Muse® Autophagy LC3 antibody-based kit. The intrinsic apoptotic pathway was investigated by measuring the cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm) function, cytochrome c levels and the activity of caspase 3/7 enzymes. Results: The results show that AlPcS4Cl-based PDT reduced cell viability, induced cytotoxicity, cell cycle arrest at the G0/G1 phase, and DNA double-strand break (DSB) through the upregulation of the ataxia telangiectasia mutated (ATM), a DNA damage sensor. In addition, the findings showed that AlPcS4Cl-based PDT induced cell death via apoptosis, which is observed through increased ROS production, reduced ΔΨm, increased cytochrome c release, and activation of caspase 3/7 enzyme. Finally, no autophagy was observed in the AlPcS4Cl-mediated PDT-treated cells. Conclusion: Our findings showed that apoptotic cell death is the main cell death mechanism triggered by AlPcS4Cl-mediated PDT in oesophageal cancer cells.

Cannabidiol Combination Enhances Photodynamic Therapy Effects on MCF-7 Breast Cancer Cells.

Cannabis sativa is a well-known plant for its psychoactive effects; however, its many derivatives, such as Cannabidiol (CBD), contain several therapeutic applications. Tetrahydrocannabinol (THC) is the main cannabis derivative responsible for psychoactive properties, while CBD is non-psychotropic. For this reason, CBD has been more exploited in the last decade. CBD has been connected to multiple anticancer properties, and when combined with photodynamic therapy (PDT), it is possible to eradicate tumors more effectively. In this study, CBD was utilized to treat MCF-7 breast cancer cells, followed by in vitro PDT combination therapy. Conventional breast cancer treatment modalities such as chemotherapy, radiotherapy, etc. have been reported for inducing a number of undesirable side effects, recurrence of the disease, and low quality of life. In this study, cells were exposed to varying concentrations of CBD (i.e., 1.25, 2.5, 5, 10, and 20 µg/mL) and incubated 12 and 24 h after treatment. The optimal doses were then used in combination therapy. Morphology and biochemical assays, including lactate dehydrogenase (LDH) for membrane integrity, adenosine triphosphate (ATP) for viability, and trypan blue exclusion assay for viability, were used to examine cellular responses after treatments. The optimal concentration was then utilized in Hypericin-Gold nanoparticles mediated PDT combination. The results revealed that, in a dose-dependent manner, conventional morphological characteristics of cell death, such as vacuolization, blebbing, and floating were observed in treated cells. The biochemical responses demonstrated an increase in LDH, a decrease in ATP, and a reduction in viability. This study demonstrated that CBD induces cell death in MCF-7 breast cancer cells cultured in vitro. The immunofluorescence results of combination therapy indicated that cell death occurred via apoptosis. In conclusion, this study proposes that the CBD and PDT combination therapy is effective in killing MCF-7 breast cancer cells in vitro by induction of apoptosis.

Nanotechnology-mediated photodynamic therapy: Focus on overcoming tumor hypoxia.

The oxygen level in the tumor is a critical marker that determines response to different treatments. Cancerous cells can adapt to hypoxia and low pH conditions within the tumor microenvironment (TME) to regulate tumor metabolism, proliferation, and promote tumor metastasis as well as angiogenesis, consequently leading to treatment failure and recurrence. In recent years, widespread attempts have been made to overcome tumor hypoxia through different methods, such as hyperbaric oxygen therapy (HBOT), hyperthermia, O2 carriers, artificial hemoglobin, oxygen generator hydrogels, and peroxide materials. While oxygen is found to be an essential agent to improve the treatment response of photodynamic therapy (PDT) and other cancer treatment modalities, the development of hypoxia within the tumor is highly associated with PDT failure. Recently, the use of nanoparticles has been a hot topic for researchers and exploited to overcome hypoxia through Oxygen-generating hydrogels, O2 nanocarriers, and O2 -generating nanoparticles. This review aimed to discuss the role of nanotechnology in tumor oxygenation and highlight the challenges, prospective, and recent advances in this area to improve PDT outcomes. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.