Photodynamic therapy (PDT) has emerged as a promising and evolving modality in cancer treatment leveraging light-sensitive compounds known as photosensitizers to selectively induce cell death in malignant tissues through the generation of reactive oxygen species (ROS). This review delves into the intricate mechanisms of PDT highlighting the pivotal role of photosensitizers and the resultant oxidative stress that damages cancer cells. It explores the versatile applications of PDT across various cancer types alongside the advantages and limitations inherent to this therapy. Recent technological advancements including improved photosensitizers and novel light delivery systems are also discussed. Additionally the review examines the critical role of arachidonic acid (AA) metabolism in cancer progression detailing the cyclooxygenase, lipoxygenase and cytochrome P450 pathways and their contributions to tumor biology. By elucidating the interplay between PDT and AA metabolism the review underscores the potential of targeting AA metabolic pathways to enhance PDT efficacy. Finally it provides clinical and translational perspectives highlighting ongoing research and future directions aimed at optimizing PDT for improved cancer treatment outcomes.
Curcumin, a bioactive compound derived from the rhizome of Curcuma longa L., has garnered significant attention for its potent anticancer properties. Despite its promising therapeutic potential, its poor bioavailability, rapid metabolism, and low water solubility hinder curcumin’s clinical application. Nanotechnology offers a viable solution to these challenges by enabling the development of curcumin-based nanoparticles (CNPs) that enhance its bioavailability and therapeutic efficacy. This review provides a comprehensive overview of the recent advancements in the design and synthesis of CNPs for cancer therapy. We discuss various NP formulations, including polymeric, lipid-based, and inorganic nanoparticles, highlighting their role in improving curcumin’s pharmacokinetic and pharmacodynamic profiles. The mechanisms by which CNPs exert anticancer effects, such as inducing apoptosis, inhibiting cell proliferation, and modulating signaling pathways, are explored in details. Furthermore, we examine the preclinical and clinical studies that have demonstrated the efficacy of CNPs in treating different types of tumors, including breast, colorectal, and pancreatic cancers. Finally, the review addresses the current challenges and future perspectives in the clinical translation of CNPs, emphasizing the need for further research to optimize their design for targeted delivery and to enhance their therapeutic outcomes. By synthesizing the latest research, this review underscores the potential of CNPs as a promising avenue for advancing cancer therapy.
Gamma-tocopherol (γ-tocopherol), a major isoform of vitamin E, exhibits potent antioxidant, anti-inflammatory, and anticancer properties, making it a promising therapeutic candidate for treating oxidative stress-related diseases. Unlike other tocopherol isoforms, γ-tocopherol effectively neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), providing robust cellular protection against oxidative damage and lipid peroxidation. Its anti-inflammatory effects are mediated through the modulation of pathways involving cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α), reducing chronic inflammation and its associated risks. In cancer therapy, γ-tocopherol demonstrates multifaceted activity, including the inhibition of tumor growth, induction of apoptosis, and suppression of angiogenesis, with significant efficacy observed in cancers such as prostate, lung, and colon. Preclinical and clinical studies support its efficacy in mitigating oxidative stress, inflammation, and cancer progression, with excellent tolerance at physiological levels. However, high doses necessitate careful evaluation to minimize adverse effects. This review consolidates current knowledge on γ-tocopherol’s biological activities and clinical implications, underscoring its importance as a natural compound for managing inflammation, oxidative stress, and cancer. As a perspective, advancements in nanoformulation technology could enhance γ-tocopherol’s bioavailability, stability, and targeted delivery, offering the potential to optimize its therapeutic application in the future.
Neutrophils, the most abundant white blood cells, play a dual role in cancer progression. While they can promote tumor growth, metastasis, and immune suppression, they also exhibit anti-tumorigenic properties by attacking cancer cells and enhancing immune responses. This review explores the complex interplay between neutrophils and the tumor microenvironment (TME), highlighting their ability to switch between pro- and anti-tumor phenotypes based on external stimuli. Pro-tumorigenic neutrophils facilitate tumor growth through mechanisms such as neutrophil extracellular traps (NETs), secretion of pro-inflammatory cytokines, and immune evasion strategies. They contribute to angiogenesis, tumor invasion, and metastasis by releasing vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Conversely, anti-tumor neutrophils enhance cytotoxicity by generating reactive oxygen species (ROS), promoting antibody-dependent cell-mediated cytotoxicity (ADCC), and activating other immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Recent advances in neutrophil-based drug delivery systems have harnessed their tumor-homing capabilities to improve targeted therapy. Neutrophil-mimicking nanoparticles and membrane-coated drug carriers offer enhanced drug accumulation in tumors, reduced systemic toxicity, and improved therapeutic outcomes. Additionally, strategies to modulate neutrophil activity, such as inhibiting their immunosuppressive functions or reprogramming them towards an anti-tumor phenotype, are emerging as promising approaches in cancer immunotherapy. Understanding neutrophil plasticity and their interactions with the TME provides new avenues for therapeutic interventions. Targeting neutrophil-mediated mechanisms could enhance existing cancer treatments and lead to the development of novel immunotherapies, ultimately improving patient survival and clinical outcomes.
Since the discovery of polyphenolic resins 150 years ago, the study of polymeric compounds named calix[n]arene has continued to progress, and those skilled in the art perfectly know now how to modulate this phenolic ring. Consequently, calix[n]arenes are now used in a large range of applications and notably in therapeutic fields. In particular, the calix[4]arene exhibits multiple possibilities for regioselective polyfunctionalization on both of its rims and offers researchers the possibility of precisely tuning the geometry of their structures. Thus, in the crucial research of new antibacterial active ingredients, the design of calixarenes finds its place perfectly. This review provides an overview of the work carried out in this aim towards the development of intrinsically active prodrogues or metallic calixarene complexes. Out of all the work of the community, there are some excellent activities emerging that could potentially place these original structures in a very good position for the development of new active ingredients.
Colorectal cancer (CRC) poses a significant challenge in healthcare, necessitating the exploration of novel therapeutic strategies. Natural compounds such as polyphenols with inherent anticancer properties have gained attention as potential therapeutic agents. This review highlights the need for novel therapeutic approaches in CRC, followed by a discussion on the synthesis of polyphenols-based nanoparticles. Various synthesis techniques, including dynamic covalent bonding, non-covalent bonding, polymerization, chemical conjugation, reduction, and metal-polyphenol networks, are explored. The mechanisms of action of these nanoparticles, encompassing passive and active targeting mechanisms, are also discussed. The review further examines the intrinsic anticancer activity of polyphenols and their enhancement through nano-based delivery systems. This section explores the natural anticancer properties of polyphenols and investigates different nano-based delivery systems, such as micelles, nanogels, liposomes, nanoemulsions, gold nanoparticles, mesoporous silica nanoparticles, and metal–organic frameworks. The review concludes by emphasizing the potential of nanoparticle-based strategies utilizing polyphenols for CRC treatment and highlights the need for future research to optimize their efficacy and safety. Overall, this review provides valuable insights into the synthesis, mechanisms of action, intrinsic anticancer activity, and enhancement of polyphenols-based nanoparticles for CRC treatment.
Resistance to conventional treatments renders urgent the discovery of new therapeutic molecules. Plant specialized metabolites such as phenolamides, a subclass of phenolic compounds, whose accumulation in tomato plants is mediated by the biotic and abiotic environment, constitute a source of natural molecules endowed with potential antioxidant, antimicrobial as well as anti-inflammatory properties. The aim of our study was to investigate whether three major phenolamides found in Tuta absoluta-infested tomato leaves exhibit antimicrobial, cytotoxic and/or anti-inflammatory properties. One of them, N1,N5,N14-tris(dihydrocaffeoyl)spermine, was specifically synthesized for this study. The three phenolamides showed low to moderate antibacterial activities but were able to counteract the LPS pro-inflammatory effect on THP-1 cells differentiated into macrophages. Extracts made from healthy but not T. absoluta-infested tomato leaf extracts were also able to reduce inflammation using the same cellular approach. Taken together, these results show that phenolamides from tomato leaves could be interesting alternatives to conventional drugs.
Cancer, characterized by the unregulated growth and dissemination of malignantly transformed cells, presents a significant global health challenge. The multistage process of cancer development involves intricate biochemical and genetic alterations within target cells. Cancer chemoprevention has emerged as a vital strategy to address this complex issue to mitigate cancer’s impact on healthcare systems. This approach leverages pharmacologically active agents to block, suppress, prevent, or reverse invasive cancer development. Among these agents, piperine, an active alkaloid with a wide range of therapeutic properties, including antioxidant, anti-inflammatory, and immunomodulatory effects, has garnered attention for its potential in cancer prevention and treatment. This comprehensive review explores piperine’s multifaceted role in inhibiting the molecular events and signaling pathways associated with various stages of cancer development, shedding light on its promising prospects as a versatile tool in cancer chemoprevention. Furthermore, the review will also delve into how piperine enhances the effectiveness of conventional treatments such as UV-phototherapy and TRAIL-based therapy, potentially synergizing with existing therapeutic modalities to provide more robust cancer management strategies. Finally, a crucial perspective of the long-term safety and potential side effects of piperine-based therapies and the need for clinical trials is also discussed.
The increased spread and persistence of bacterial drug-resistant phenotypes remains a public health concern and has contributed significantly to the challenge of combating antibiotic resistance. Nanotechnology is considered an encouraging strategy in the fight against antibiotic-resistant bacterial infections; this new strategy should improve therapeutic efficacy and minimize side effects. Evidence has shown that various nanomaterials with antibacterial performance, such as metal-based nanoparticles (i.e., silver, gold, copper, and zinc oxide) have intrinsic antibacterial properties. These antibacterial agents, such as those made of metal oxides, carbon nanomaterials, and polymers, have been used not only to improve antibacterial efficacy but also to reduce bacterial drug resistance due to their interaction with bacteria and their photophysical properties. These nanostructures have been used as effective agents for photothermal therapy (PTT) and photodynamic therapy (PDT) to kill bacteria locally by heating or the controlled production of reactive oxygen species. Additionally, PTT or PDT therapies have also been combined with photoacoustic (PA) imaging to simultaneously improve treatment efficacy, safety, and accuracy. In this present review, we present, on the one hand, a summary of research highlighting the use of PTT-sensitive metallic nanomaterials for the treatment of bacterial and fungal infections, and, on the other hand, an overview of studies showing the PA-mediated theranostic functionality of metal-based nanomaterials.
Bazzania trilobata (L.) Gray is a leafy liverwort from the family of Lepidoziaceae, well known for its antifungal properties. In this study, the 70% ethanol and methanol extracts of B. trilobata were investigated for new in vitro biological activities of cosmetic interest. The results showed that the total phenol content, the DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity, and the anti-collagenase activity of the 70% ethanol extract were higher than for methanol. The methanol extract showed mild tyrosinase inhibitory activity and antimicrobial properties towards the Gram-positive bacteria Enterococcus faecalis. Lignans, coumarins, and bis-bibenzyls were the major classes of phenolic constituents tentatively identified in both extracts. In addition, a known drimenyl caffeate was identified in B. trilobata and its structure was confirmed by NMR spectroscopy. These results suggest that extracts from B. trilobata could be exploited as an interesting new source of natural active ingredients for cosmetic applications.
Prostate cancer is a major health concern worldwide, and current treatments, such as surgery, radiation therapy, and chemotherapy, are associated with significant side effects and limitations. Photodynamic therapy (PDT) is a promising alternative that has the potential to provide a minimally invasive and highly targeted approach to treating prostate cancer. PDT involves the use of photosensitizers (PSs) that are activated by light to produce reactive oxygen species (ROS), which can induce tumor cell death. There are two main types of PSs: synthetic and natural. Synthetic PSs are classified into four generations based on their structural and photophysical properties, while natural PSs are derived from plant and bacterial sources. Combining PDT with other therapies, such as photothermal therapy (PTT), photoimmunotherapy (PIT), and chemotherapy (CT), is also being explored as a way to improve its efficacy. This review provides an overview of conventional treatments for prostate cancer, the underlying principles of PDT, and the different types of PSs used in PDT as well as ongoing clinical studies. It also discusses the various forms of combination therapy being explored in the context of PDT for prostate cancer, as well as the challenges and opportunities associated with this approach. Overall, PDT has the potential to provide a more effective and less invasive treatment option for prostate cancer, and ongoing research is aimed at improving its selectivity and efficacy in clinical settings.
Amphotericin B is the oldest antifungal molecule which is still currently widely used in clinical practice, in particular for the treatment of invasive diseases, even though it is not devoid of side effects (particularly nephrotoxicity). Recently, its redox properties (i.e., both prooxidant and antioxidant) have been highlighted in the literature as mechanisms involved in both its activity and its toxicity. Interestingly, similar properties can be described for inorganic nanoparticles. In the first part of the present review, the redox properties of Amphotericin B and inorganic nanoparticles are discussed. Then, in the second part, inorganic nanoparticles as carriers of the drug are described. A special emphasis is given to their combined redox properties acting either as a prooxidant or as an antioxidant and their connection to the activity against pathogens (i.e., fungi, parasites, and yeasts) and to their toxicity. In a majority of the published studies, inorganic nanoparticles carrying Amphotericin B are described as having a synergistic activity directly related to the rupture of the redox homeostasis of the pathogen. Due to the unique properties of inorganic nanoparticles (e.g., magnetism, intrinsic anti-infectious properties, stimuli-triggered responses, etc.), these nanomaterials may represent a new generation of medicine that can synergistically enhance the antimicrobial properties of Amphotericin B.
Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/β-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA’s low bioavailability, emphasizing the need for enhanced therapeutic strategies.
Conventional antimicrobial susceptibility testing (AST) methods require 24-48 h to provide results, creating the need for a probabilistic antibiotic therapy that increases the risk of antibiotic resistance emergence. Consequently, the development of rapid AST methods has become a priority. Over the past decades, sedimentation field-flow fractionation (SdFFF) has demonstrated high sensitivity in early monitoring of induced biological events in eukaryotic cell populations. This proof-of-concept study aimed at investigating SdFFF for the rapid assessment of bacterial susceptibility to antibiotics. Three bacterial species were included (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) with two panels of antibiotics tailored to each bacterial species. The results demonstrate that SdFFF, when used in "Hyperlayer" elution mode, enables monitoring of antibiotic-induced morphological changes. The percentage variation of the retention factor (PΔR) was used to quantify the biological effect of antibiotics on bacteria with the establishment of a threshold value of 16.8% to differentiate susceptible and resistant strains. The results obtained with SdFFF were compared to that of the AST reference method, and a categorical agreement of 100% was observed. Overall, this study demonstrates the potential of SdFFF as a rapid method for the determination of antibiotic susceptibility or resistance since it is able to provide results within a shorter time frame than that needed for conventional methods (3-4 h vs 16-24 h, respectively), enabling earlier targeted antibiotic therapy. Further research and validation are necessary to establish the effectiveness and reliability of SdFFF in clinical settings.
Maslinic acid- and oleanolic acid-based hyrids with potent antibacterial and antibiofilm activities were designed and semi-synthesized from pentacyclic triterpene acids isolated from olive oil manufacturing solid waste.
The emergence of multidrug-resistant (MDR) bacteria in recent years has been alarming and represents a major public health problem. The development of effective antimicrobial agents remains a key challenge. Nanotechnologies have provided opportunities for the use of nanomaterials as components in the development of antibacterial agents. Indeed, metal-based nanoparticles (NPs) show an effective role in targeting and killing bacteria via different mechanisms, such as attraction to the bacterial surface, destabilization of the bacterial cell wall and membrane, and the induction of a toxic mechanism mediated by a burst of oxidative stress (e.g., the production of reactive oxygen species (ROS)). Considering the lack of new antimicrobial drugs with novel mechanisms of action, the induction of oxidative stress represents a valuable and powerful antimicrobial strategy to fight MDR bacteria. Consequently, it is of particular interest to determine and precisely characterize whether NPs are able to induce oxidative stress in such bacteria. This highlights the particular interest that NPs represent for the development of future antibacterial drugs. Therefore, this review aims to provide an update on the latest advances in research focusing on the study and characterization of the induction of oxidative-stress-mediated antimicrobial mechanisms by metal-based NPs.
Antimicrobial resistance is a major public health issue raising growing concern in the face of dwindling response options. It is therefore urgent to find new anti-infective molecules enabling us to fight effectively against ever more numerous bacterial infections caused by ever more antibiotic-resistant bacteria. In this quest for new antibacterials, essential oils (or compounds extracted from essential oils) appear to be a promising therapeutic option. In the present work, we investigate the potential antibacterial synergy between a combination of terpinen-4-ol and α-terpineol (10:1) compared to standard tea tree oil. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. Then, time kill assays, in vitro cytotoxicity and bactericidal activity on latent bacteria (persisters) were investigated. Finally, an in silico study of the pharmacokinetic parameters of α-terpineol was also performed. Altogether, our data demonstrate that the combination of terpinen-4-ol and α-terpineol might be a precious weapon to address ESKAPE pathogens.
During a previous study that identified plants used in traditional medicine in Togo to treat infectious diseases, Daniellia oliveri was specifically reported to treat intertrigo and candidiasis. Consequently, to explore the anti-infective potential of this plant, we investigated the antibacterial and the antifungal activity of the plant’s parts, as well as the cytotoxic activities of raw extracts and subsequent fractions, and the chemical composition of the most active fractions. In order to evaluate the antimicrobial activity, MICs were determined using the broth dilution method. Then, the most active fractions were evaluated for cytotoxicity by using normal human cells (MRC-5 cells) via the MTT assay. Finally, the most active and not toxic fractions were phytochemically investigated by GC-MS. Interestingly, all the raw extracts and fractions were active against the bacteria tested, with MICs ranging from 16 µg/mL to 256 µg/mL, while no antifungal activity was observed at 256 µg/mL, the highest tested concentration. Moreover, no toxicity was observed with most of the active fractions. The subsequent chemical investigation of the most interesting fractions led to identifying terpenes, phytosterols, phenolic compounds, and fatty acids as the main compounds. In conclusion, this study demonstrated that D. oliveri possesses valuable antibacterial activities in accordance with traditional use.
Les compétences sociales se travaillent tout au long de la vie et doivent s’apprendre au plus tôt car elles sont indispensables dans la vie professionnelle. La coopération notamment est une compétence essentielle dans une entreprise et c’est pour cela qu’elle est utilisée comme moyen pédagogique dans la formation proposée par les deux programmes Initiatives d’Excellences en Formations Innovantes (IDEFI). Ceux-ci se sont associés pour proposer aux étudiants en L2 Sciences pour la Santé de l’Université de Lorraine de « booster leur réussite » par le développement des compétences sociales. Grâce à une semaine de formation basée sur la coopération, les étudiants ont pu travailler leurs compétences sociales et augmenter leur confiance en eux.
In this study, we investigated the chemical composition, antioxidant and antibacterial activities of essential oil and aqueous extract from Thymus algeriensis Boiss. & Reut growing in Tunisia. GC/MS analysis of essential oil from the aerial part of the plant led to identifying 54 constituents representing 96.87 % of the total oil composition. Monoterpenes represented the major components of the essential oil. On the other hand, the aqueous extract and the essential oil were screened for their antioxidant and antibacterial activities. The latter was assessed against Gram-negative and Gram-positive bacterial strains using the broth dilution micro method for the determination of antibacterial activity. The antioxidant activity was evaluated using the DPPH scavenging activity and Ferric Reducing/Antioxidant Power (FRAP) assays. The essential oil was found to be more active in antibacterial screening (MIC = 0.54 mu g/mL). Whereas the aqueous extract exhibited the most potent antioxidant activity with (IC50 = 0.04 mu g/mL). UHPLC ESI(-)-HRMS/MS analysis of the aqueous extract allowed tentative identification of its constituents and showed that it is rich in phenolic compounds. Luteolin-glucuronide was found to be the most abundant compound followed by Vicenin-2 and Apigenin-diglucuronide.