Добірка наукової літератури з теми "Purpurin-18"

How to make cancer treatment more efficient and enhance the patient’s outcome? By multimodal therapy, theranostics, or personalized medicine? These are questions asked by scientists and doctors worldwide. However, finding new unique approaches and options for cancer treatment as well as new selective therapeutics is very challenging. More frequently, researchers “go back in time” and use already known and well-described compounds/drugs, the structure of which further derivatize to “improve” their properties, extend the use of existing drugs to new indications, or even to obtain a completely novel drug. Natural substances, especially marine products, are a great inspiration in the discovery and development of novel anticancer drugs. These can be used in many modern approaches, either as photo- and sonosensitizers in photodynamic and sonodynamic cancer therapy, respectively, or in tumor imaging and diagnosis. This review is focused on a very potent natural product, the chlorophyll metabolite purpurin 18, and its derivatives, which is well suitable for all the mentioned applications. Purpurin 18 can be easily isolated from green plants of all kinds ranging from seaweed to spinach leaves and, thus, it presents an economically feasible source for a very promising anticancer drug.

Purpurin 18 derivatives with a polyethylene glycol (PEG) linker were synthesized as novel photosensitizers (PSs) with the goal of using them in photodynamic therapy (PDT) for cancer. These compounds, derived from a second-generation PS, exhibit absorption at long wavelengths; considerable singlet oxygen generation and, in contrast to purpurin 18, have higher hydrophilicity due to decreased logP. Together, these properties make them potentially ideal PSs. To verify this, we screened the developed compounds for cell uptake, intracellular localization, antitumor activity and induced cell death type. All of the tested compounds were taken up into cancer cells of various origin and localized in organelles known to be important PDT targets, specifically, mitochondria and the endoplasmic reticulum. The incorporation of a zinc ion and PEGylation significantly enhanced the photosensitizing efficacy, decreasing IC50 (half maximal inhibitory compound concentration) in HeLa cells by up to 170 times compared with the parental purpurin 18. At effective PDT concentrations, the predominant type of induced cell death was apoptosis. Overall, our results show that the PEGylated derivatives presented have significant potential as novel PSs with substantially augmented phototoxicity for application in the PDT of cervical, prostate, pancreatic and breast cancer.

Research and synthesis of photosensitive purpurin 18 (Pp-18) from nature is one of the topics that many research groups are interested in and developing. In this study, the authors defined some characteristics of Pp-18 synthesised from chlorophyll a - a substance isolated from Spirulina. The results showed that Pp-18 had good dispersion in acetone at 478.5 nm (R2=0.98285) and reached 98%. Fluorescence spectroscopy of Pp-18 in acetone was measured at a concentration of 70 ppm, wavelengths 365.39, 417.62, and 557.96 nm. The fluorescence lifetime of Pp-18 in acetone solution was 2.85 ns.

In this work, we obtained the first selenium-containing chlorin with a chalcogen atom in exlocycle E. It was shown that the spectral properties were preserved in the target compound and the stability increased at two different pH values, in comparison with the starting purpurin-18. The derivatives have sufficiently high fluorescence and singlet oxygen quantum yields. The photoinduced cytotoxicity of sulfur- and selenium-anhydrides of chlorin p6 studied for the first time in vitro on the S37 cell line was found to be two times higher that of purpurin-18 and purpurinimide studied previously. Moreover, the dark cytotoxicity increased four-fold in comparison with the latter compounds. Apparently, the increase in the dark cytotoxicity is due to the interaction of the pigments studied with sulfur- and selenium-containing endogenous intracellular compounds. Intracellular distributions of thioanhydride and selenoanhydride chlorin p6 in S37 cells were shown in cytoplasm by diffusion distribution. The intracellular concentration of the sulfur derivative turned out to be higher and, as a consequence, its photoinduced cytotoxicity was higher as well.

A new type of water soluble ionic photosensitizer (PS), purpurin-18-N-methyl-D-glucamine (Pu-18-NMGA) has been synthesized and it was conjugated into gold nanoparticles (GNPs) stabilized by the PS without adding any particular reducing agents and surfactants. In vitro anticancer efficacy of the PS and its PS–GNPs conjugate against A549 lung cancer cell lines was evaluated. The PS–GNPs conjugate based on water-soluble Pu-18-NMGA afforded good PDT efficacy which was three times greater than that of the water-soluble PS.

Le cancer colorectal (CCR) est l'une des tumeurs malignes les plus diagnostiquées au monde, et les modalités thérapeutiques conventionnelles actuelles sont souvent invasives, résistantes et induisent des effets secondaires toxiques sur les tissus sains. C’est pourquoi de nouvelles approches thérapeutiques ciblées se développent. Dans cette optique, on trouve la thérapie photodynamique (PDT) qui présente plusieurs avantages évidents par rapport aux modalités classiques, telles qu'une invasivité minimale, une grande sélectivité vis-à-vis des tissus cancéreux et moins d'effets secondaires. La PDT est une alternative thérapeutique approuvée cliniquement et actuellement utilisée pour plusieurs tumeurs solides, déclenchant la mort cellulaire par la génération d'espèces réactives de l'oxygène(ERO). Cependant, la nature hydrophobe de la plupart des photosensibilisateurs (PS) utilisés, tels que les chlorines, limite l'efficacité globale de la PDT. Pour surmonter cette limitation, l'utilisation de nanovecteurs semble être une approche puissante. Dans cette perspective, nous avons récemment développé des nanoparticules organiques fluorescentes (FONP) solubles dans l'eau et biocompatibles, fonctionnalisées avec de la purpurine-18 (Pp-18) et son dérivé, la chlorine p6 (Cp6), en tant que nouveaux agents de PDT. L’objectif de cette étude a été de déterminer in vitro le potentiel phototoxiquedes FONPs[Cp6] dans le traitement des modèles cellulaires 2D et 3D de lignées du CCR. Nos résultats montrent des effets phototoxiques importants des FONPs[Cp6], médiés par la génération des ERO intracellulaires dans les cellules de CCR HCT116 et HT-29. En outre après la PDT, nous avons prouvé que les FONP[Cp6] induisent l'apoptose par la voie mitochondriale intrinsèque, mais également l’autophagie. Notre travail démontre l'activité photodynamique de ces nanoparticules, ce qui en fait des candidats prometteurs pour le traitement du CCR
Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide, and current conventional therapeutic modalities are often invasive, resistant, and induce toxic side effects on healthy tissue. This is why new targeted therapeutic approaches are being developed. One such approach is photodynamic therapy (PDT), which offers several advantages over conventional modalities, such as minimal invasiveness, high selectivity towards cancerous tissue, and fewer side effects. PDT is a clinically-approved therapeutic alternative currently used for several solid tumors, triggering cell death through the generation of reactive oxygen species (ROS). However, the hydrophobic nature of most of the photosensitizers (PS) used, such as chlorines, limits the overall efficacy of PDT. To overcome this limitation, the use of nanovectors appears to be a powerful approach.With this in mind, we have recently developed water-soluble and biocompatible fluorescent organic nanoparticles (FONPs) functionalized with purpurin-18 (Pp-18) and its derivative, chlorin p6 (Cp6), as novel PDT agents. This study aimed to determine in vitro the phototoxic potential of FONPs[Cp6] in treating 2D and 3D cell models of CRC lines. Our results show significant phototoxic effects of FONPs[Cp6], mediated by the generation of intracellular ROS in HCT116 and HT-29 CRC cells. Furthermore, after PDT, we demonstrated that FONPs[Cp6] induce apoptosis via the intrinsic mitochondrial pathway and autophagy. Our work demonstrates the photodynamic activity of these nanoparticles, making them promising candidates for the treatment of CRC