title: Smart pH-responsive nanocarriers based on nano-graphene oxide for combined chemo- and photothermal therapy overcoming drug resistance.
abstract: A pH-responsive nanocarrier is developed by coating nanoscale graphene oxide (NGO) with dual types of polymers, polyethylene glycol (PEG) and poly(allylamine hydrochloride) (PAH), the latter of which is then modified with 2,3-dimethylmaleic anhydride (DA) to acquire pH-dependent charge reversibility. After loading with doxorubicin (DOX), a chemotherapy drug, the obtained NGO-PEG-DA/DOX complex exhibits a dual pH-responsiveness, showing markedly enhanced cellular uptake under the tumor microenvironmental pH, and accelerated DOX release under a further lowered pH inside cell lysosomes. Combining such a unique behavior with subsequently slow efflux of DOX, NGO-PEG-DA/DOX offers remarkably improved cell killing for drug-resistant cancer cells under the tumor microenvironmental pH in comparison with free DOX. Exploiting its excellent photothermal conversion ability, combined chemo- and photothermal therapy is further demonstrated using NGO-PEG-DA/DOX, realizing a synergistic therapeutic effect. This work presents a novel design of surface chemistry on NGO for the development of smart drug delivery systems responding to the tumor microenvironment and external physical stimulus, with the potential to overcome drug resistance.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.forename: Kunyang
authors.initials: K
authors.lastname: Li
authors.forename: Xiaoze
authors.initials: X
authors.lastname: Shi
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007834:Lasers; D061986:MCF-7 Cells; D008299:Maleic Anhydrides / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008299:Maleic Anhydrides; D010087:Oxides; D011092:Polyethylene Glycols; C007474:2,3-dimethylmaleic anhydride; D006108:Graphite; D004317:Doxorubicin
keywords: charge reverse; drug resistance; nanoscale graphene oxides; pH sensitive; photothermal therapy