Editing Glutathione (section)

==In degradation of drug delivery systems==
Among various types of [[cancer]], [[lung cancer]], [[larynx cancer]], [[mouth cancer]], and [[breast cancer]] exhibit higher concentrations (10-40 mM) of GSH compared to healthy cells.<ref>{{cite journal |vauthors=Gamcsik MP, Kasibhatla MS, Teeter SD, Colvin OM |title=Glutathione levels in human tumors |journal=Biomarkers |volume=17 |issue=8 |pages=671–91 |date=December 2012 |pmid=22900535 |pmc=3608468 |doi=10.3109/1354750X.2012.715672 }}</ref> Thus, [[drug delivery systems]] containing [[disulfide bond]]s, typically cross-linked micro-nanogels, stand out for their ability to degrade in the presence of high concentrations of glutathione (GSH).<ref>{{cite journal |vauthors=Patra JK, Das G, Fraceto LF, Campos EV, Rodriguez-Torres MD, Acosta-Torres LS, Diaz-Torres LA, Grillo R, Swamy MK, Sharma S, Habtemariam S, Shin HS |title=Nano based drug delivery systems: recent developments and future prospects |journal=J Nanobiotechnology |volume=16 |issue=1 |pages=71 |date=September 2018 |pmid=30231877 |pmc=6145203 |doi=10.1186/s12951-018-0392-8 |doi-access=free}}</ref> This degradation process releases the drug payload specifically into cancerous or tumorous tissue, leveraging the significant difference in redox potential between the oxidizing extracellular environment and the reducing intracellular cytosol.<ref>{{cite journal |vauthors=Li Y, Maciel D, Rodrigues J, Shi X, Tomás H |title=Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery |journal=Chem Rev |volume=115 |issue=16 |pages=8564–8608 |date=August 2015 |pmid=26259712 |doi=10.1021/cr500131f }}</ref><ref>{{cite journal |vauthors=Adamo G, Grimaldi N, Campora S, Sabatino MA, Dispenza C, Ghersi G |title=Glutathione-Sensitive Nanogels for Drug Release |journal=Chemical Engineering Transactions |volume=38 |pages=457–462 |date=2014 |doi= |url=https://www.cetjournal.it/index.php/cet/article/view/5682}}</ref>

When internalized by [[endocytosis]], nanogels encounter high concentrations of GSH inside the cancer cell. GSH, a potent reducing agent, donates electrons to disulfide bonds in the nanogels, initiating a thiol-disulfide exchange reaction. This reaction breaks the disulfide bonds, converting them into two thiol groups, and facilitates targeted drug release where it is needed most. This reaction is called a thiol-disulfide exchange reaction.<ref>{{cite book |first=H.F. |last=Gilbert |chapter=Molecular and Cellular Aspects of Thiol–Disulfide Exchange |title=Advances in Enzymology and Related Areas of Molecular Biology |publisher= |volume=63 |date=1990 |isbn=978-0-470-12309-6 |pages=69–172 |doi=10.1002/9780470123096.ch2 |pmid=2407068}}</ref><ref>{{cite book |first=H.F. |last=Gilbert |chapter=Thiol/disulfide exchange equilibria and disulfide bond stability |title=Biothiols, Part A: Monothiols and Dithiols, Protein Thiols, and Thiyl Radicals |series=Methods in Enzymology |publisher= |volume=251 |date=1995 |isbn=978-0-12-182152-4 |pages=8–28 |doi=10.1016/0076-6879(95)51107-5 |pmid=7651233}}</ref>
:::::::::::''R−S−S−R′''+ 2''GSH'' → ''R−SH + R′−SH'' + ''GSSG''
where ''R'' and ''R''' are parts of the micro-nanogel structure, and ''GSSG'' is oxidized glutathione (glutathione disulfide).

The breaking of disulfide bonds causes the nanogel to degrade into smaller fragments. This degradation process leads to the release of encapsulated drugs. The released drug molecules can then exert their therapeutic effects, such as inducing [[apoptosis]] in cancer cells.<ref>{{cite journal |vauthors=Elkassih SA, Kos P, Xiong H, Siegwart DJ |title=Degradable redox-responsive disulfide-based nanogel drug carriers via dithiol oxidation polymerization |journal=Biomater Sci |volume=7 |issue=2 |pages=607–617 |date=January 2019 |pmid=30462102 |pmc=7031860 |doi=10.1039/c8bm01120f }}</ref>