학술논문
Assessment of the effects of amphiphilic poly (N-vinylpyrrolidone) nanoparticles loaded with bortezomib on glioblastoma cell lines and zebrafish embryos
Document Type
Academic Journal
Author
Yagolovich, Anne V.; Kuskov, Andrey N.; Kulikov, Pavel P.; Bagrov, Dmitry V.; Petrova, Polina A.; Kukovyakina, Ekaterina V.; Isakova, Alina A.; Khan, Irina I.; Pokrovsky, Vadim S.; Nosyrev, Alexander E.; Stamati, Polyxeni C.; Markvicheva, Elena A.; Gasparian, Marine E.; Spandidos, Demetrios A.; Tsatsakis, Aristidis M.
Source
Biomedical Reports. March 2024, Vol. 20 Issue 3, p1b, 12 p.
Subject
Language
English
ISSN
2049-9434
Abstract
Introduction The prominent antitumor potential of proteasome inhibitors was discovered in 1999 and immediately attracted attention of scientists and medical oncologists (1). The first-in-class proteasome inhibitor bortezomib (Velcade[R]) became one [...]
Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in vitro in monolayer tumor cell cultures (I[C.sub.50] ~6.5 [micro] g/ml) and in 3D multicellular tumor spheroids (I[C.sub.50] ~8.5 g/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects in vivo were studied in zebrafish Danio rerio embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases.
Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types of cancer, primarily in solid tumors, is limited due to poor pharmacokinetics, inefficient tissue penetration, low stability and frequent adverse effects. In the present study, a novel micellar nano-scaled delivery system was manufactured, composed of amphiphilic poly(N-vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar nanoparticles loaded with prothionamide, a drug without anticancer effect, were used as control. The size and zeta potential of the obtained polymeric micelles were measured by dynamic light scattering. Bortezomib-loaded micelles exhibited significant cytotoxic activity in vitro in monolayer tumor cell cultures (I[C.sub.50] ~6.5 [micro] g/ml) and in 3D multicellular tumor spheroids (I[C.sub.50] ~8.5 g/ml) of human glioblastoma cell lines U87 and T98G. Additionally, the toxic effects in vivo were studied in zebrafish Danio rerio embryos, with an estimated 50% lethal concentration of 0.1 mg/ml. Considering that bortezomib and other molecules from the class of proteasome inhibitors are potent antitumor agents, nanodelivery approach can help reduce adverse effects and expand the range of its applications for treatment of various oncological diseases.