Redox-responsive star-shaped magnetic micelles with active-targeted and magnetic-guided functions for cancer therapy

Publication date: Available online 30 June 2016
Source:Acta Biomaterialia
Author(s): Zhaomin Tang, Lei Zhang, Yi Wang, Dan Li, Zhendong Zhong, Shaobing Zhou
Highly efficient delivery of therapeutic agents to target sites is of great importance for achieving excellent therapeutic efficacy in cancer treatment. Here, we report a redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions. The magnetic star-shaped micelles are formed by self-assembly of four-arm poly(ethylene glycol) (PEG)-poly(ε-caprolactone) (PCL) copolymers with disulfide bonds as intermediate linkers. Anticancer drug doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) are simultaneously encapsulated into the hydrophobic cores. PBA ligands are chemically conjugated to the end of the hydrophilic PEG segments, endowing the active targeting of nanocarriers. Both qualitative and quantitative analyses of the intracellular uptake of these micelles with active-targeting and dual-targeting are performed in vitro by cultured with salic acid (SA)-positive tumor cells (human liver carcinoma cell line HepG2, human cervical cancer cell line HeLa) and SA-negative tumor cells (human breast adenocarcinoma cell line MCF-7, human non-small cell lung cancer cell line A549) in the presence or absence of a permanent magnetic field. In vivo biodistribution studies with active-targeting and dual-targeting and in vivo anti-tumor effect are carried out in detail after being applied to the BALB/c mice bearing mouse H22 hepatocarcinoma cells tumor model. These in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulate around the tumor tissues by the magnetic-guiding and in turn are taken up by the tumor cells through SA-mediated endocytosis, leading to a high therapeutic efficacy to the artificial solid tumor.Statement of SignificanceA redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions was developed. Both qualitative and quantitative analysis of the intracellular uptake with dual-targeting of these micelles were performed in vitro by salic acid (SA)-positive tumor cells. The in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulated around the tumor tissues, leading to a high therapeutic efficacy to artificial solid tumor.

Graphical abstract

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