title: Mixed-charge nanoparticles for long circulation, low reticuloendothelial system clearance, and high tumor accumulation.
abstract: Mixed-charge zwitterionic surface modification shows great potential as a simple strategy to fabricate nanoparticle (NP) surfaces that are nonfouling. Here, the in vivo fate of 16 nm mixed-charge gold nanoparticles (AuNPs) is investigated, coated with mixed quaternary ammonium and sulfonic groups. The results show that mixed-charge AuNPs have a much longer blood half-life (≈30.6 h) than do poly(ethylene glycol) (PEG, M¯w = 2000) -coated AuNPs (≈6.65 h) and they accumulate in the liver and spleen far less than do the PEGylated AuNPs. Using transmission electron microscopy, it is further confirmed that the mixed-charge AuNPs have much lower uptake and different existing states in liver Kupffer cells and spleen macrophages one month after injection compared with the PEGylated AuNPs. Moreover, these mixed-charge AuNPs do not cause appreciable toxicity at this tested dose to mice in a period of 1 month as evidenced by histological examinations. Importantly, the mixed-charge AuNPs have higher accumulation and slower clearance in tumors than do PEGylated AuNPs for times of 24-72 h. Results from this work show promise for effectively designing tumor-targeting NPs that can minimize reticuloendothelial system clearance and circulate for long periods by using a simple mixed-charge strategy.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Liu
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Chen
authors.forename: Qiao
authors.initials: Q
authors.lastname: Jin
authors.forename: Kefeng
authors.initials: K
authors.lastname: Ren
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007624:KB Cells; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D012157:Mononuclear Phagocyte System / Q000378:metabolism*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006046:Gold
keywords: biodistribution; blood circulation; gold nanoparticles; mixed-charge zwitterionic; tumor accumulation