Type

Journal Article

Authors

Jochen H M Prehn
Sally-Ann Cryan
Holger N Lode
Ella L Kim
Andrew W Boyd
Bryan W Day
Brett W Stringer
Jann N Sarkaria
Jenny L Pokorny
Gemma O'Connor
and 3 others

Subjects

Microbiology

Topics
cell line tumor aromatase inhibitors drug therapy letrozole cell movement antibodies monoclonal nanoparticles triazoles polyglycolic acid ganglioside gd2 brain neoplasms drug effects nitriles transfection cell proliferation glioblastoma humans antineoplastic agents lactic acid hela cells administration dosage polylactic acid polyglycolic acid copolymer immunotoxins gangliosides immunology

Anti-GD2-ch14.18/CHO coated nanoparticles mediate glioblastoma (GBM)-specific delivery of the aromatase inhibitor, Letrozole, reducing proliferation, migration and chemoresistance in patient-derived GBM tumor cells. (2016)

Abstract Aromatase is a critical enzyme in the irreversible conversion of androgens to oestrogens, with inhibition used clinically in hormone-dependent malignancies. We tested the hypothesis that targeted aromatase inhibition in an aggressive brain cancer called glioblastoma (GBM) may represent a new treatment strategy. In this study, aromatase inhibition was achieved using third generation inhibitor, Letrozole, encapsulated within the core of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs). PLGA-NPs were conjugated to human/mouse chimeric anti-GD2 antibody ch14.18/CHO, enabling specific targeting of GD2-positive GBM cells. Treatment of primary and recurrent patient-derived GBM cells with free-Letrozole (0.1 μM) led to significant decrease in cell proliferation and migration; in addition to reduced spheroid formation. Anti-GD2-ch14.18/CHO-NPs displayed specific targeting of GBM cells in colorectal-glioblastoma co-culture, with subsequent reduction in GBM cell numbers when treated with anti-GD2-ch14.18-PLGA-Let-NPs in combination with temozolomide. As miR-191 is an estrogen responsive microRNA, its expression, fluctuation and role in Letrozole treated GBM cells was evaluated, where treatment with premiR-191 was capable of rescuing the reduced proliferative phenotype induced by aromatase inhibitor. The repurposing and targeted delivery of Letrozole for the treatment of GBM, with the potential role of miR-191 identified, provides novel avenues for target assessment in this aggressive brain cancer.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Sally-Ann Cryan, Holger N Lode, Ella L Kim, Andrew W Boyd, Bryan W Day, Brett W Stringer, Jann N Sarkaria, Jenny L Pokorny, Gemma O'Connor and 3 others

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 70
 
3
A W Boyd
Royal College of Surgeons in Ireland
Total Publications: 3
 
4
B W Day
Royal College of Surgeons in Ireland
Total Publications: 3
 
5
B W Stringer
Royal College of Surgeons in Ireland
Total Publications: 3
 
6
Gemma O'Connor
Royal College of Surgeons in Ireland
Total Publications: 5