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Mixed‐Charge Nanoparticles for Long Circulation, Low Reticuloendothelial System Clearance, and High Tumor Accumulation
Author(s) -
Liu Xiangsheng,
Li Huan,
Chen Yangjun,
Jin Qiao,
Ren Kefeng,
Ji Jian
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300617
Subject(s) - mononuclear phagocyte system , ethylene glycol , nanoparticle , colloidal gold , materials science , peg ratio , spleen , biophysics , nanotechnology , chemistry , medicine , immunology , organic chemistry , finance , economics , biology
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.