Chitosan was modified with lipoic acid and nanoparticles thereof were made.By treating the nanoparticles with a catalytic amount of dithiothreitol (DTT)

chitosan nanoparticles with disulfide-crosslinkages were obtained.The incorporation of disulfide crosslinkages not only endowed the nanoparticles with reductive-responsive property

but also introduced hydrophobic moiety.Hydrophobic anticancer agent doxorubicin and fluorescent probe fluorescein

respectively

were loaded into the nanoparticles through hydrophobic interactions.The formation of disulfide crosslinkages significantly slowed the release of loaded doxorubicin in a medium without reductive agent (mimicking low reductive environment in blood).In the presence of 10 mmol/L DTT

which mimicked the intracellular high glutathione concentration

doxorubicin released rapidly from the crosslinked nanoparticles because the disulfide crosslinkages were reduced and broken.Flow cytometry assay showed that the cellular uptake of the crosslinked nanoparticles increased when the medium pH deceased from 7.4 (blood and normal tissue pH) to 7.0

6.8 and 6.5 (mimicking tumor acidic environment).This can be attributed to the neutral and hydrophilic surfaces of the nanoparticles at neutral environment

and the positively charged surfaces at acidic pHs

which was supported by zeta potential data.Cytotocicity assay indicated that doxorubicin-loaded crosslinked nanoparticles showed higher cytotocicity against HeLa cells at pH 6.5 than at pH 7.4.