Citation: He-ze Guo, Sheng Song, Ting-ting Dai, Sheng-li Li, Hong-jing Dou. Trypsin-responsive Near-infrared Fluorescent/Magnetic Resonance Dual-imaging Composite Nanospheres Based on Self-assembly[J]. Acta Polymerica Sinica, ;2018, 0(8): 1127-1140. doi: 10.11777/j.issn1000-3304.2018.18079 shu

Trypsin-responsive Near-infrared Fluorescent/Magnetic Resonance Dual-imaging Composite Nanospheres Based on Self-assembly

  • Corresponding author: Hong-jing Dou, hjdou@sjtu.edu.cn
  • Received Date: 12 March 2018
    Revised Date: 16 April 2018
    Available Online: 15 June 2018

  • The trypsin-responsive near-infrared fluorescent/magnetic resonance dual-imaging composite nanospheres, which consist of PAA-decorated Fe3O4 magnetic nanoparticles (MNPs) that serve as the magnetic resonance imaging (MRI) agents and Cy5.5-modified poly-L-lysine (Cy5.5-PLL) as the trypsin-responsive substrate and fluorescent carrier, were successfully fabricated via self-assembly method. The MNPs present negatively charge due to the carboxyl groups from PAA on their surface and the Cy5.5-PLL present positively charge due to the amino groups in PLL chains. The construction of the composite nanospheres was initially performed via the self-assembly driven by the electrostatic interactions between the above mentioned oppositely charged precursors. Subsequently, glutaraldehyde (GA) was introduced to partially crosslink the amino groups in PLL and stabilize the nanospheres. The fluorescent and magnetic characterization of the two precursors of the composite nanospheres, Cy5.5-PLL and MNPs, indicated that Cy5.5-PLL chains showed obvious fluorescent signal and the MNPs displayed the superparamagnetism property. However, the notable fluorescent signal from Cy5.5-PLL in native soluble state was self-quenched thanks to the short distance among the Cy5.5 fluorescent molecules after the construction of the nanospheres. Additionally, the structure of the as-prepared self-assembled nanospheres was stable, resulting from the almost unchanged results of the hydrodynamic size and fluorescence intensity of nanospheres in different buffer solutions. Nevertheless, because of the sensitivity of PLL chains to trypsin, the nanospheres were selectively disintegrated into fragmented segments under the hydrolysis by trypsin, leading to 18-fold amplification of fluorescent intensity in comparison with the self-assembled nanospheres in quenched state. Moreover, the magnetic resonance imaging enhancement was also related to the disintegration of the nanospheres. As expected, the trypsin-positive cells incubated with nanospheres exhibited remarkable fluorescent imaging due to the disintegration of the nanospheres into debris, whereas this disintegration did not take place for the trypsin-negative cells. In vivo fluorescent images of the composite nanospheres in normal nude mice further verified the trypsin-triggered fluorescent imaging. Cytotoxicity study demonstrated that the composite nanospheres presented low toxicity to several cell lines, and exhibited remarkable near-infrared fluorescent/magnetic resonance imaging capabilities, which were sensitive to the presence of trypsin and thus provided excellent opportunity to serve as dual-imaging agents.
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