title: Reversibly extracellular pH controlled cellular uptake and photothermal therapy by PEGylated mixed-charge gold nanostars.
abstract: Shielding nanoparticles from nonspecific interactions with normal cells/tissues before they reach and after they leave tumors is crucial for the selective delivery of NPs into tumor cells. By utilizing the reversible protonation of weak electrolytic groups to pH changes, long-chain amine/carboxyl-terminated polyethylene glycol (PEG) decorated gold nanostars (GNSs) are designed, exhibiting reversible, significant, and sensitive response in cell affinity and therapeutic efficacy to the extracellular pH (pHe) gradient between normal tissues and tumors. This smart nanosystem shows good dispersity and unimpaired photothermal efficacy in complex bioenvironment at pH 6.4 and 7.4 even when their surface charge is neutral. One PEGylated mixed-charge GNSs with certain surface composition, GNS-N/C 4, exhibits high cell affinity and therapeutic efficacy at pH 6.4, and low affinity and almost "zero" damage to cells at pH 7.4. Remarkably, this significant and sensitive response in cell affinity and therapeutic efficacy is reversible as local pH alternated. In vivo, GNS-N/C 4 shows higher accumulation in tumors and improved photothermal therapeutic efficacy than pH-insensitive GNSs. This newly developed smart nanosystem, whose cell affinity reversibly transforms in response to pHe gradient with unimpaired biostability, provides a novel effective means of tumor-selective therapy.
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, P.R. China; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, P.R. China.
authors.forename: Shouju
authors.initials: S
authors.lastname: Wang
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Teng
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Dingbin
authors.initials: D
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.forename: Huangxian
authors.initials: H
authors.lastname: Ju
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
mesh_terms: D002462:Cell Membrane / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000627:therapeutic use*; D004058:Diffusion; D045604:Extracellular Fluid / Q000737:chemistry; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; D006046:Gold
keywords: PEGylated mixed-charge nanoparticles; controllable cellular uptake; photothermal therapy; reversibly pH responsive; tumor-targeted delivery