Lys05 induces lysosomal membrane permeabilization and increases radiosensitivity in glioblastoma

Zhou, Wei; Guo, Yulian; Zhang, Xin; Jiang, Zheng

doi:10.1002/jcb.29437

Cited by 34 publications

(29 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lysosome is the intracellular target of some nanomaterials and its permeabilization is involved in material-mediated cell death [35]. Inhibiting lysosome function enhances the antitumor activity of chemotherapeutic drugs and increases the sensitivity of tumors to radiotherapy [36,37]. We employed the acridine orange (AO) dye to stain 4T1 cells.…”

Section: Antitumor Evaluation In Vitromentioning

confidence: 99%

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane-camouflaged antitumor nanoparticles

et al. 2020

View full text Add to dashboard Cite

Background: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated. Results: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation increased the proportions of G2/M phase and Caveolin-1 content in 4T1 breast cancer cells, contributing to an endocytic enhancement of PINPs@PM. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

show abstract

Section: Antitumor Evaluation In Vitromentioning

confidence: 99%

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane-camouflaged antitumor nanoparticles

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The PI3K inhibitors 3MA ( 96 ), wortmannin, and LY294002 have also been used as autophagy inhibitors based on their inhibitory effect on PIK3C3 activity, which is essential for induction of autophagy ( 37 ). Lys05 is a newly synthetic lysosomotropic agent that has anti-glioma activity by inducing lysosomal membrane permeabilization and inhibition of autophagy, resulting in decreased cell viability and cell growth, as well as radiosensitivity of glioma U251 and LN229 cells ( 97 ).…”

Section: Prospect-targeting Autophagy In Glioblastoma Therapymentioning

confidence: 99%

Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors

Qin

Zhang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Glioblastoma (GB) is the most malignant and aggressive form of brain tumor, characterized by frequent hyperactivation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. PI3K/AKT/mTOR inhibitors have a promising clinical efficacy theoretically. However, strong drug resistance is developed in GB against the PI3K/AKT/mTOR inhibitors due to the cytoprotective effect and the adaptive response of autophagy during the treatment of GB. Activation of autophagy by the PI3K/AKT/mTOR inhibitors not only enhances treatment sensitivity but also leads to cell survival when drug resistance develops in cancer cells. In this review, we analyze how to increase the antitumor effect of the PI3K/AKT/mTOR inhibitors in GB treatment, which is achieved by various mechanisms, among which targeting autophagy is an important mechanism. We review the dual role of autophagy in both GB therapy and resistance against inhibitors of the PI3K/AKT/mTOR signaling pathway, and further discuss the possibility of using combinations of autophagy and PI3K/AKT/mTOR inhibitors to improve the treatment efficacy for GB. Finally, we provide new perspectives for targeting autophagy in GB therapy.

show abstract

“…Lysosomes are considered therapeutic targets to treat many diseases including lupus, rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, and cancers [30,31]. Inhibiting lysosome function enhances the antitumor activity of chemotherapeutic drugs and increases the sensitivity of tumors to radiotherapy [32,33]. We employed the acridine orange (AO) dye to stain 4T1 cells.…”

Section: Antitumor Evaluation In Vitromentioning

confidence: 99%

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane- camouflaged antitumor nanoparticles

Chen

Shen

Han

et al. 2019

Preprint

View full text Add to dashboard Cite

Backgroud: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated.Results: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation enabled the endocytic enhancement of PINPs@PM by 4T1 breast cancer cells. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

show abstract

Lys05 induces lysosomal membrane permeabilization and increases radiosensitivity in glioblastoma

Cited by 34 publications

References 40 publications

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane-camouflaged antitumor nanoparticles

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane-camouflaged antitumor nanoparticles

Therapeutic Potential of Autophagy in Glioblastoma Treatment With Phosphoinositide 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin Signaling Pathway Inhibitors

Irradiation pretreatment enhances the therapeutic efficacy of platelet-membrane- camouflaged antitumor nanoparticles

Contact Info

Product

Resources

About