title: Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery systems.
abstract: Considering the specific pH gradients of tumour microenvironments, a dual acid-responsive drug delivery system, which can respond to the tumor extracellular and intercellular pH stimuli, has been fabricated via simple host-guest recognition. Firstly, we synthesise 2,4,6-trimethoxybenzaldehyde modified dextran (Dex-TMBA) and mPEG-imine-β-cyclodextrin (PIC), respectively. And then, through the host-guest recognition between the cyclodextrin (CD) of PIC and the benzene ring of Dex-TMBA, a kind of dual acid-responsive supramolecular drug delivery system can be fabricated. Under neutral pH conditions, anticancer drugs can be loaded by forming supramolecular nanoparticles via the host-guest recognition. While, at tumor extracellular pH (∼6.8), the acid-labile benzoic-imine of PIC cleaves and the nanoparticles are amino positively charged to facilitate cell internalization. Subsequently, due to the hydrolysis of acetal bonds in Dex-TMBA under significantly increased acidity in subcellular compartments such as the endosomes (∼5.3), the loaded doxorubicin releases from the endocytosed drug delivery. This dual acid-responsive nanoparticles can efficiently load and release drugs, acting as drug delivery systems for enhancing anticancer efficiency.
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China. chenl686@nenu.edu.cn.
authors.forename: Chunran
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China. chenl686@nenu.edu.cn.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China. chenl686@nenu.edu.cn.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. China. chenl686@nenu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China. clhe@ciac.jl.cn.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D002470:Cell Survival; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C000613705:2,4,6-trimethoxybenzaldehyd; D000970:Antineoplastic Agents; D001547:Benzaldehydes; D047392:beta-Cyclodextrins; D011092:Polyethylene Glycols; D004317:Doxorubicin