Search Results (409)

Colorectal cancer (CRC) is the third most common cancer in the world, with an ongoing rising incidence. Despite secure advancements in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. Among the main challenges with current photosensitizers (PS), hydrophobicity and low selective uptake by the tumor remain prominent. Thus, developing an optimal design for PS to improve their solubility and enhance their selective accumulation in cancer cells is crucial for enhancing the efficacy of PDT. Targeted photoactivation triggers the production of reactive oxygen species (ROS), which promote oxidative stress within cancer cells and ultimately lead to their death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anticancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies, which lodge porphin PS in their inner cavity, and tested them as PDT agents on the HCT116 and HT-29 human CRC cell lines. The cellular internalization of the porphin-loaded assemblies was confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, inducing apoptosis through caspase activation and cell cycle progression disruptions. These findings suggest that arene-Ru assemblies lodging porphin PS are potent candidates for PDT of CRC. Full article

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT’s efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments. Full article

Photodynamic therapy (PDT) is a therapeutic modality that depends on the interaction of light, photosensitizers, and oxygen. The photon absorption and energy transfer process can lead to the Type II photochemical reaction of the photosensitizer and the production of singlet oxygen (¹O₂), which strongly oxidizes and reacts with biomolecules, ultimately causing oxidative damage to the target cells. Therefore, ¹O₂ is regarded as the key photocytotoxic species accountable for the initial photodynamic reactions for Type II photosensitizers. This article will provide a comprehensive review of ¹O₂ properties, ¹O₂ production, and ¹O₂ detection in the PDT process. The available ¹O₂ data of regulatory-approved photosensitizing drugs will also be discussed. Full article

Bacterial DNA gyrase is considered one of the validated targets for antibacterial drug discovery. Benzopyrones have been reported as promising derivatives that inhibit bacterial DNA gyrase B through competitive binding into the ATP binding site of the B subunit. In this study, we designed and synthesized twenty-two benzopyrone-based derivatives with different chemical features to assess their antimicrobial and photosensitizing activities. The antimicrobial activity was evaluated against B. subtilis, S. aureus, E. coli, and C. albicans. Compounds 6a and 6b (rigid tetracyclic-based derivatives), 7a-7f (flexible-linker containing benzopyrones), and 8a-8f (rigid tricyclic-based compounds) exhibited promising results against B. subtilis, S. aureus, and E. coli strains. Additionally, these compounds demonstrated photosensitizing activities against the B. subtilis strain. Both in silico molecular docking and in vitro DNA gyrase supercoiling inhibitory assays were performed to study their potential mechanisms of action. Compounds 8a-8f exhibited the most favorable binding interactions, engaging with key regions within the ATP binding site of the DNA gyrase B domain. Moreover, compound 8d displayed the most potent IC₅₀ value (0.76 μM) compared to reference compounds (novobiocin = 0.41 μM and ciprofloxacin = 2.72 μM). These results establish a foundation for structure-based optimization targeting DNA gyrase inhibition with antibacterial activity. Full article

Polyamines play a pivotal role in cancer cell proliferation. The excessive polyamine requirement of these malignancies is satisfied through heightened biosynthesis and augmented extracellular uptake via the polyamine transport system (PTS) present on the cell membrane. Meanwhile, photodynamic therapy (PDT) emerges as an effective anti-cancer treatment devoid of drug resistance. Recognizing these intricacies, our study devised a novel polyamine-derived photosensitizer (PS) for targeted photodynamic treatment, focusing predominantly on pancreatic cancer cells. We synthesized and evaluated novel spermine-derived fluorescent probes (N2) and PS (N3), exhibiting selectivity towards pancreatic cancer cells via PTS. N3 showed minimal dark toxicity but significant phototoxicity upon irradiation, effectively causing cell death in vitro. A significant reduction in tumor volume was observed post-treatment with no pronounced dark toxicity using the pancreatic cancer CDX mouse model, affirming the therapeutic potential of N3. Overall, our findings introduce a promising new strategy for cancer treatment, highlighting the potential of polyamine-derived PSs in PDT. Full article

The combination of photodynamic therapy (PDT) and pneumatotherapy is emerging as one of the most effective strategies for increasing cancer treatment efficacy while minimizing side effects. Photodynamic forces affect nitric oxide (NO) levels as activated photosensitizers produce NO, and NO levels in the tumor and microenvironment directly impact tumor cell responsiveness to PDT. In this paper, 3-benzenesulfonyl-4-(1-hydroxy ether)-1,2,5-oxadiazole-2-oxide NO donor–silicon phthalocyanine coupling (SiPc–NO) was designed and prepared into self-assembled nanoparticles (SiPc–NO@NPs) by precipitation method. By further introducing arginyl-glycyl-aspartic acid (RGD) on the surface of nanoparticles, NO-photosensitizer delivery systems (SiPc–NO@RGD NPs) with photo-responsive and tumor-targeting properties were finally prepared and preliminarily evaluated in terms of their formulation properties, NO release, and photosensitizing effects. Furthermore, high reactive oxygen species (ROS) generation efficiency and high PDT efficiency in two breast cancer cell lines (human MCF-7 and mouse 4T1) under irradiation were also demonstrated. The novel SiPc–NO@RGD NPs show great potential for application in NO delivery and two-photon bioimaging-guided photodynamic tumor therapy. Full article

In cancer therapy, it is essential to selectively release cytotoxic agents into the tumor to prevent the adverse effects associated with anticancer drugs. Thus, in this study, a stimuli-sensitive polymer–drug conjugate was synthesized for selective drug release. Doxorubicin (DOX) and docetaxel (DTX) were conjugated onto novel poly(jasmine lactone) based copolymer via a thioketal (TK) linker. In addition, a photosensitizer (chlorin e6) was attached to the polymer, which served as a reactive oxygen species generator to cleave the TK linker. The conjugate is readily self-assembled into micelles less than 100 nm in size. Micelles demonstrate a notable increase in their ability to cause cell death when exposed to near-infrared (NIR) light on MDA-MB-231 breast cancer cells. The increase in cytotoxicity is higher than that observed with the combination of free DOX and DTX. The accumulation of DOX in the nucleus after release from the micelles (laser irradiation) was also confirmed by confocal microscopy. In the absence of light, micelles did not show any toxicity while the free drugs were found toxic irrespective of the light exposure. The obtained results suggest the targeted drug delivery potential of micelles regulated by the external stimuli, i.e., NIR light. Full article

The increasing incidence of breast cancers (BCs) in the world population and their complexity and high metastatic ability are serious concerns for healthcare systems. Despite the significant progress in medicine made in recent decades, the efficient treatment of invasive cancers still remains challenging. Chemotherapy, a fundamental systemic treatment method, is burdened with severe adverse effects, with efficacy limited by resistance development and risk of disease recurrence. Also, current diagnostic methods have certain drawbacks, attracting attention to the idea of developing novel, more sensitive detection and therapeutic modalities. It seems the solution for these issues can be provided by nanotechnology. Particularly, quantum dots (QDs) have been extensively evaluated as potential targeted drug delivery vehicles and, simultaneously, sensing and bioimaging probes. These fluorescent nanoparticles offer unlimited possibilities of surface modifications, allowing for the attachment of biomolecules, such as antibodies or proteins, and drug molecules, among others. In this work, we discuss the potential applicability of QDs in breast cancer diagnostics and treatment in light of the current knowledge. We begin with introducing the molecular and histopathological features of BCs, standard therapeutic regimens, and current diagnostic methods. Further, the features of QDs, along with their uptake, biodistribution patterns, and cytotoxicity, are described. Based on the reports published in recent years, we present the progress in research on possible QD use in improving BC diagnostics and treatment efficacy as chemotherapeutic delivery vehicles and photosensitizing agents, along with the stages of their development. We also address limitations and open questions regarding this topic. Full article

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy. Full article

Natural photosensitizers (PS) are compounds derived from nature, with photodynamic properties. Natural PSs have a similar action to that of commercial PSs, where cancer cell death occurs by necrosis, apoptosis, and autophagy through ROS generation. Natural PSs have garnered great interest over the last few decades because of their high biocompatibility and good photoactivity. Specific wavelengths could cause phytochemicals to produce harmful ROS for photodynamic therapy (PDT). However, natural PSs have some shortcomings, such as reduced solubility and lower uptake, making them less appropriate for PDT. Nanotechnology offers an opportunity to develop suitable carriers for various natural PSs for PDT applications. Various nanoparticles have been developed to improve the outcome with enhanced solubility, optical adsorption, and tumor targeting. Multidrug resistance (MDR) is a phenomenon in which tumor cells develop resistance to a wide range of structurally and functionally unrelated drugs. Over the last decade, several researchers have extensively studied the effect of natural PS-based photodynamic treatment (PDT) on MDR cells. Though the outcomes of clinical trials for natural PSs were inconclusive, significant advancement is still required before PSs can be used as a PDT agent for treating MDR tumors. This review addresses the increasing literature on MDR tumor progression and the efficacy of PDT, emphasizing the importance of developing new nano-based natural PSs in the fight against MDR that have the required features for an MDR tumor photosensitizing regimen. Full article

As a novel therapeutic approach, photothermal therapy (PTT) combined with chemotherapy can synergistically produce antitumor effects. Herein, dithiodipropionic acid (DTDP) was used as a donor of disulfide bonds sensitive to the tumor microenvironment for establishing chemical bonding between the photosensitizer indocyanine green amino (ICG-NH₂) and acidified single-walled carbon nanotubes (CNTs). The CNT surface was then coated with conjugates (HD) formed by the targeted modifier hyaluronic acid (HA) and 1,2-tetragacylphosphatidyl ethanolamine (DMPE). After doxorubicin hydrochloride (DOX), used as the model drug, was loaded by CNT carriers, functional nano-delivery systems (HD/CNTs-SS-ICG@DOX) were developed. Nanosystems can effectively induce tumor cell (MCF-7) death in vitro by accelerating cell apoptosis, affecting cell cycle distribution and reactive oxygen species (ROS) production. The in vivo antitumor activity results in tumor-bearing model mice, further verifying that HD/CNTs-SS-ICG@DOX inhibited tumor growth most significantly by mediating a synergistic effect between chemotherapy and PTT, while various functional nanosystems have shown good biological tissue safety. In conclusion, the composite CNT delivery systems developed in this study possess the features of high biocompatibility, targeted delivery, and responsive drug release, and can achieve the efficient coordination of chemotherapy and PTT, with broad application prospects in cancer treatment. Full article

Obesity is a global epidemic which induces a multitude of metabolic disorders. Browning of white adipose tissue (WAT) has emerged as a promising therapeutic strategy for promoting weight loss and improving associated metabolic syndromes in people with obesity. However, current methods of inducing white adipose tissue browning have limited applicability. We developed a nanocomplex pTSL@(P+I), which is a temperature-sensitive liposome (TSL) surface-conjugated with an adipocyte-targeting peptide (p) and loaded with both browning-promoting agents (P) and photosensitizing agents (I). This nanocomplex exhibits adipocyte targeting, as well as synergistic pharmacological and photothermal properties to promote browning. pTSL@(P+I) effectively upregulates UCP1 and COX5B expression by activating the transcription axis of PPARγ/PGC1α and HSF1/PGC1α, thereby promoting white adipose tissue browning and reducing obesity. This novel nanocomplex exhibited a uniform spherical shape, with an average diameter of approximately 200 nm. Additionally, the nanocomplexes exhibited remarkable photothermal properties and biocompatibility. Further, when adipocytes were treated with pTSL@(P+I), their triglyceride content decreased remarkably and intracellular mitochondrial activity increased significantly. When applied to diet-induced obesity (DIO) mice, the nanocomplex exhibited significant efficacy, demonstrating a notable 14.4% reduction in body weight from the initial measurement, a decreased fat/lean mass ratio of 20.8%, and no statistically significant disparities (p > 0.05) in associated side effects when compared to the control group. In summary, implementation of the targeted nanocomplex pTSL@(P+I) to enhance energy expenditure by stimulating white adipose tissue browning offers a promising therapeutic approach for the treatment of obesity and related metabolic syndromes. Full article

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. As MNTs are composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module appears advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNT_N) or a C-terminal (MNT_C) part were developed by genetic engineering. Both new MNTs demonstrated a high affinity for target receptors, as revealed by fluorescent-labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNT_N possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNT_N was significantly higher than when attached to either MNT_C or the original MNTs. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1. Full article

The present review explores the underlying mechanisms of phytophotodermatitis, a non-immunologic skin reaction triggered by certain plants followed by exposure to ultraviolet radiation emitted by sunlight. Recent research has advanced our understanding of the pathophysiology of phytophotodermatitis, highlighting the interaction between plant-derived photosensitizing compounds (e.g., furanocoumarins and psoralens) and ultraviolet light leading to skin damage (e.g., erythema, fluid blisters, edema, and hyperpigmentation), identifying these compounds as key contributors to the phototoxic reactions causing phytophotodermatitis. Progress in understanding the molecular pathways involved in the skin’s response to these compounds has opened avenues for identifying potential therapeutic targets suitable for the management and prevention of this condition. The review emphasizes the importance of identifying the most common phototoxic plant families (e.g., Apiaceae, Rutaceae, and Moraceae) and plant species (e.g., Heracleum mantegazzianum, Ruta graveolens, Ficus carica, and Pastinaca sativa), as well as the specific phytochemical compounds responsible for inducing phytophototoxicity (e.g., limes containing furocoumarin have been linked to lime-induced photodermatitis), underscoring the significance of recognizing the dangerous plant sources. Moreover, the most used approaches and tests for accurate diagnosis such as patch testing, Wood’s lamp examination, or skin biopsy are presented. Additionally, preventive measures such as adequate clothing (e.g., long-sleeved garments and gloves) and treatment strategies based on the current knowledge of phytophotodermatitis including topical and systemic therapies are discussed. Overall, the review consolidates recent findings in the field, covering a diverse array of phototoxic compounds in plants, the mechanisms by which they trigger skin reactions, and the implications for clinical management. By synthesizing these insights, we provide a comprehensive understanding of phytophotodermatitis, providing valuable information for both healthcare professionals and researchers working to address this condition. Full article

Photodynamic therapy (PDT) is an effective method for treating microbial infections by leveraging the unique photophysical properties of photosensitizing agents, but issues such as fluorescence quenching and the restricted generation of reactive oxygen species (ROS) under hypoxic conditions still remain. In this study, we successfully synthesized and designed a coumarin-based aggregation-induced emission luminogen (AIEgen), called ICM, that shows a remarkable capacity for type I ROS and type II ROS generation. The ¹O₂ yield of ICM is 0.839. The ROS it produces include hydroxyl radicals (HO^•) and superoxide anions (O₂^•−), with highly effective antibacterial properties specifically targeting Staphylococcus aureus (a Gram-positive bacterium). Furthermore, ICM enables broad-spectrum fluorescence imaging and exhibits excellent biocompatibility. Consequently, ICM, as a potent type I photosensitizer for eliminating pathogenic microorganisms, represents a promising tool in addressing the threat posed by these pathogens. Full article