A new type of glutathione-responsive anti-osteosarcoma prodrug nanoparticles

ABSTRACT

In this study, we grafted hydrophilic γ-polyglutamic acid (γ-PGA) with the hydrophobic drug methotrexate (MTX) to develop an amphiphilic and stimuli-responsive nanoparticles (MTX-SS-PGA NPs). The average size and zeta potential for MTX-SS-PGA NPs were 100.5 nm and −20.4 mV. In vitro drug release, the MTX cumulative release of nanoparticles within 72 h, which was more robust at 10 mM GSH (90.1%) than normal physiological environment pH 7.4 (9.8%). The disulphide bond was easily cleaved by glutathione, which subsequently led to the disintegration of the nanoparticle structure and the release of MTX. In cell studies, 10 μM MTX-SS-PGA NPs was efficient taken up into the cancer cell, released MTX in a redox-responsive manner, and exhibited cytotoxicity as potent as MTX.Moreover, 10 μM MTX-SS-PGA NPs have little side effects on normal cells. Overall, this new type of glutathione-responsive anti-osteosarcoma prodrug nanoparticles is promising for efficient drug delivery.

KEYWORDS:

• Self-assembly
• nanostructures
• amphiphilic
• γ-polyglutamic acid
• stimuli-responsive nanoparticles
• osteosarcoma

Disclosure statement

The authors declared that we have no conflicts of interest to this work.

Additional information

Funding

This work was supported by the Natural Science Foundation of Hunan Province, China [2018JJ2267] to Chunlian He; Hunan province college students research learning and innovative experiment project [S202010542052] to Lewei Li; the Natural Science Foundation of Hubei Province of China [2018CFB522] to Qiufang Zhang; the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research [WDCM2019001] to Xiaojun Tao.