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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. [ABSTRACT FROM AUTHOR]

Marine biodiversity provides a range of diverse biological resources, including seafoods that are rich in protein and a well-balanced amino acid composition. Previous studies have shown that peptides can improve bone formation and/or inhibit bone resorption, suggesting the potential for seafood bioactive peptides (SBPs) in development of food and pharmaceuticals for management of osteoporosis. In this review, we provided an up-to-date overview of the anti-osteoporosis activity of SBPs and describe their underlying molecular mechanisms. We focus on SBPs' development, broadening the scope and depth of research, as well as strengthening in vivo and clinical research. In vitro cell cultures and in vivo animal osteoporosis models have demonstrated the potential for seafood-derived SBPs, including fish, mollusks, crustaceans, seaweed and microalgae, in preventing osteoporosis. These peptides may act by activating the signaling pathways, such as BMP/Smads, MAPK, OPG/RANKL/RANK, and NF-κB, which are associated with modulation bone health. [ABSTRACT FROM AUTHOR]