Original ArticleTargeted delivery of anticancer drugs by aptamer AS1411 mediated Pluronic F127/cyclodextrin-linked polymer composite micelles
Graphical Abstract
A novel composite micelle (CM) with surface modification of aptamer AS1411 (Ap) was successfully developed for targeted delivery of doxorubicin (DOX) to human breast tumors. Mixing of two different kinds of polymers afforded the composite micelle-Ap (CM-Ap) various desirable physicochemical properties. In addition, the in vitro and in vivo studies demonstrated that the DOX-loaded CM-Ap could prolong blood circulation time, enhance cellular uptake and cytotoxicity, and consequently, improve tumor growth inhibition and minimize adverse effect.
Section snippets
Materials and reagents
Pluronic F127 (MW 12,500) was kindly supplied by BASF China Ltd. (Shanghai, China). Monomethoxy poly (ethylene glycol) (MPEG, Mn 5000) and tin (II) 2-ethylhexanoate (Sn(Oct)2) were purchased from Sigma Aldrich. d,l-lactide was obtained from Shandong Institute of Medical Instruments (Shandong, China). Beta cyclodextrin (β-CD) was purchased from Shanghai Chemical Reagents Co. Ltd. (Shanghai, China) and recrystallized before use. Rhodamine B (RhB) was purchased from Aladin Ltd. (Shanghai, China).
Synthesis and characterization of polymers
The aptamer-conjugated Pluronic F127 (Pluronic F127-Ap) was obtained by the reaction of 5’-NH2-AS1411 with dicarboxylated Pluronic F127. From the urea PAGE images (Figure 2, B), we could observe that the free aptamer had a clear migration on the gel and the Pluronic F127 had no band on the PAGE gel. The Pluronic F127-Ap (MR = 2.84) showed a clear band at the origin site, and no band at the free aptamer site. The Pluronic F127-Ap (MR = 5.69) showed a clearer and brighter band at the origin site, and
Discussion
Nowadays, ligand-modified nanoparticles have been considered to effectively improve the anti-tumor efficacy based on enhanced accumulation at tumor tissues via EPR effect and subsequent endocytosis of tumor cells via ligand–receptor interaction. As one of the most excellent targeting ligands, aptamers can selectively bind to a variety of targets ranging from small molecules to whole cells due to their three-dimensional structures. In the present study, we constructed a binary composite micelles
Acknowledgment
The authors thank Yangmin Jin for animal experiments.
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Conflict of interest statement: No conflict of interest is reported by the authors of this paper.
Funding sources: This work was supported by National Natural Science Funds for Excellent Young Scholar (81222047), National Natural Science Funds (81473173), the Ph.D. Program Foundation of Ministry of Education of China (J20110026), and the Ministry of Education Program for New Century Excellent Talents (NCET-11-0454).