Mitochondrion-Targeted NIR Therapeutic Agent Suppresses Melanoma by Inducing Apoptosis and Cell Cycle Arrest via E2F/Cyclin/CDK Pathway DOI Creative Commons
Changzhen Sun,

Jianv Wang,

Tong Xia

и другие.

Pharmaceuticals, Год журнала: 2022, Номер 15(12), С. 1589 - 1589

Опубликована: Дек. 19, 2022

Malignant melanoma is the most fatal form of skin cancer worldwide, and earlier diagnosis more effective therapies are required to improve prognosis. As a possible solution, near-infrared fluorescent heptamethine cyanine dyes have been shown be useful for tumor treatment. Here, we synthesized novel theranostic agent, IR-817, multifunctional bioactive small-molecule that has emission, targets mitochondria in cells, selective anti-cancer effects. In vitro experiments, IR-817 preferentially accumulated cells through organic anion transporting polypeptide transporters but also selectively inhibited growth by inducing mitochondrial-dependent intrinsic apoptosis. Mechanistically, caused G0/G1 cell cycle arrest targeting E2F/Cyclin/CDK pathway. Finally, significantly suppressed xenograft tumors zebrafish mice. Immunohistochemical staining hematoxylin eosin revealed induced apoptosis proliferation without notable side Therefore, mitochondrial-targeting agent may promising accurate diagnosis, real-time monitoring, safe treatments.

Язык: Английский

Hypoxia and its effect on the cellular system DOI

Dipali Rahane,

Tannu Dhingra,

Guruswami Chalavady

и другие.

Cell Biochemistry and Function, Год журнала: 2024, Номер 42(2)

Опубликована: Янв. 27, 2024

Abstract Eukaryotic cells utilize oxygen for different functions of cell organelles owing to cellular survival. A balanced homeostasis is an essential requirement maintain the regulation normal systems. Any changes in level are stressful and can alter expression regulatory genes proteins. Lack or hypoxia results oxidative stress formation inducible factors (HIF) reactive species (ROS). Substantial damages due have been reported play a major role various pathological conditions. There studies which demonstrated that system disrupted by hypoxia. Currently, study on effects following important field research as it not only helps decipher signaling pathway modulation, but also explore novel therapeutic strategies. On basis beneficial effect preconditioning organelles, many investigations ongoing promising disease management strategy near future. Hence, present review discusses about mechanisms their involvement progression diseases.

Язык: Английский

Процитировано

6
Targeting the organelle for radiosensitization in cancer radiotherapy DOI Creative Commons

Xiaoyan Sun,

Lin-Jie Wu, Lina Du

и другие.

Asian Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер 19(2), С. 100903 - 100903

Опубликована: Март 11, 2024

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low energy deposition, severe damage surrounding normal cells, and high tumor resistance radiation. Among various radiotherapy methods, boron neutron capture (BNCT) emerged as principal approach improve the therapeutic ratio of malignancies reduce lethality tissue, but it remains deficient in terms insufficient accumulation well short retention time, which limits curative effect. Recently, series radiosensitizers that can selectively accumulate specific organelles cells have been developed precisely target radiotherapy, thereby reducing side effects tissue damage, overcoming radioresistance, improving radiosensitivity. In review, we mainly focus on field nanomedicine-based discuss organelle-targeted radiosensitizers, specifically nucleus, mitochondria, endoplasmic reticulum lysosomes. Furthermore, carriers used BNCT are particularly presented. Through demonstrating recent developments radiosensitization, hope provide insight into design clinical treatment.

Язык: Английский

Процитировано

6
Peptide-based strategies for overcoming multidrug-resistance in cancer therapy DOI
Xiaofang Luo, Ye Wu, Xiao-kun Zhang

и другие.

Chinese Chemical Letters, Год журнала: 2024, Номер 36(1), С. 109724 - 109724

Опубликована: Март 7, 2024

Язык: Английский

Процитировано

5
Multifunctional Near-Infrared Dye IR-817 Encapsulated in Albumin Nanoparticles for Enhanced Imaging and Photothermal Therapy in Melanoma DOI Creative Commons

Jianv Wang,

Hongye Liao,

Jieming Ban

и другие.

International Journal of Nanomedicine, Год журнала: 2023, Номер Volume 18, С. 4949 - 4967

Опубликована: Сен. 1, 2023

Background: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, toxic side effects. As an effective biologic drug carrier, albumin combines with to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues are widely used in tumor photothermal therapy. Methods: Herein, a newly synthesized near-infrared dye IR-817 was combined bovine serum (BSA) create BSA@IR-817 Through detection of emission absorption, optimal concentration ratio BSA were determined. Subsequently, dynamic light scattering (DLS) measurements scanning electron microscopy (SEM) for physical characterization Finally, vitro vivo experiments conducted assess therapeutic potential Results: adsorbed onto carrier by covalent conjugation supramolecular encapsulation, resulting formation dispersed, homogeneous, stable particle size range 120– 220 nm. not only improved poor effects enhanced absorption peaks region, well visible spectrum. In addition, laser 808 irradiation able convert energy into heat temperatures exceeding 50 °C. By creating mouse model subcutaneous melanoma, it discovered that inhibition rate greater than 99% after achieved nearly complete ablation without causing significant toxicity. Conclusion: Our research, therefore, proposes use safe imaging, diagnosis, treatment offers promising strategy future biomedical applications. Keywords: albumin, dyes, therapy, melanoma

Язык: Английский

Процитировано

7
Emerging roles of lysosome homeostasis (repair, lysophagy and biogenesis) in cancer progression and therapy DOI
Nitish Chauhan, Birija Sankar Patro

Cancer Letters, Год журнала: 2023, Номер 584, С. 216599 - 216599

Опубликована: Дек. 20, 2023

Язык: Английский

Процитировано

7
Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma DOI Creative Commons
Ida Eriksson, Linda Vainikka, Petra Wäster

и другие.

Journal of Investigative Dermatology, Год журнала: 2023, Номер 143(9), С. 1769 - 1778.e12

Опубликована: Март 4, 2023

Lysosomes are central in cell homeostasis and participate macromolecular degradation, plasma membrane repair, exosome release, adhesion/migration, apoptosis. In cancer, alterations lysosomal function spatial distribution may facilitate disease progression. this study, we show enhanced activity malignant melanoma cells compared with that normal human melanocytes. Most lysosomes perinuclear location melanocytes, while they more dispersed melanoma, retained proteolytic low pH also the peripheral population. Rab7a expression is lower than by increasing Rab7a, relocated to region melanoma. Exposure lysosome-destabilizing drug L-leucyl-L-leucine methyl ester causes higher damage subset of melanomas, whereas differences subpopulation susceptibility cannot be found Interestingly, recruit endosomal sorting complex required for transport-III core protein CHMP4B, involved rather initiate lysophagy. However, when position promoted overexpression or kinesore treatment, lysophagy increased. addition, accompanied reduced migration capacity. Taken together, study emphasizes properties phenotype declares targeting as a future therapeutic approach.

Язык: Английский

Процитировано

6
Spatiotemporal profiling defines persistence and resistance dynamics during targeted treatment of melanoma DOI Open Access
Jill C. Rubinstein, Sergii Domanskyi, Todd Sheridan

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 5, 2024

Abstract Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability cells enter a persister state, evade treatment with relative dormancy, and repopulate tumor when reactivated. Using spatial transcriptomics in patient derived xenograft models, we capture clonal lineage evolution during treatment, finding state show increased oxidative phosphorylation, decreased proliferation, invasive capacity, central-to-peripheral gradients. Phylogenetic tracing identifies intrinsic- acquired-resistance mechanisms (e.g. dual specific phosphatases, Reticulon-4, CDK2) suggests temporal windows potential therapeutic efficacy. deep learning analyze histopathological slides, find morphological features cell states, demonstrating that juxtaposition histology data enables identification phenotypically-distinct populations using imaging alone. In summary, define change selection melanoma spatiotemporal resolution, elucidating how choice timing agents will impact eradicate resistant clones. Statement Significance Tumor is accelerated by application anti-cancer therapy, resulting expansions leading dormancy subsequently resistance, but dynamics this process are incompletely understood. Tracking progression identify conserved, global transcriptional changes local clone-clone patterns underlying emergence resistance.

Язык: Английский

Процитировано

1
Mitochondrion-Targeted NIR Therapeutic Agent Suppresses Melanoma by Inducing Apoptosis and Cell Cycle Arrest via E2F/Cyclin/CDK Pathway DOI Creative Commons
Changzhen Sun,

Jianv Wang,

Tong Xia

и другие.

Pharmaceuticals, Год журнала: 2022, Номер 15(12), С. 1589 - 1589

Опубликована: Дек. 19, 2022

Malignant melanoma is the most fatal form of skin cancer worldwide, and earlier diagnosis more effective therapies are required to improve prognosis. As a possible solution, near-infrared fluorescent heptamethine cyanine dyes have been shown be useful for tumor treatment. Here, we synthesized novel theranostic agent, IR-817, multifunctional bioactive small-molecule that has emission, targets mitochondria in cells, selective anti-cancer effects. In vitro experiments, IR-817 preferentially accumulated cells through organic anion transporting polypeptide transporters but also selectively inhibited growth by inducing mitochondrial-dependent intrinsic apoptosis. Mechanistically, caused G0/G1 cell cycle arrest targeting E2F/Cyclin/CDK pathway. Finally, significantly suppressed xenograft tumors zebrafish mice. Immunohistochemical staining hematoxylin eosin revealed induced apoptosis proliferation without notable side Therefore, mitochondrial-targeting agent may promising accurate diagnosis, real-time monitoring, safe treatments.

Язык: Английский

Процитировано

7