Peihong Ni*a(倪沛红)
a College of Chemistry, Chemical Engineering and Materials Science, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Soochow University, Suzhou 215123, P. R. China
Polym. Chem. 2015, 6, 3205-3216
To prevent the disassembly of drug-loaded micelles under the high dilution conditions of the bloodstream, one of the efficient methods is to achieve the cross-linkage inside the micellar core. In this study, we have developed a kind of novel folate-conjugated core cross-linked polyphosphoester micelle with acid-cleavable acetal groups (ACCL-FA). These polyphosphoester-based cross-linked micelles possessed a much smaller size and enhanced stability compared to the uncross-linked (UCL) counterpart, and also showed good biodegradability and low cytotoxicity. The in vitro release studies revealed that the doxorubicin (DOX)-loaded ACCL micelles showed excellent stability with minimal drug release under neutral conditions, and displayed fast micellar dissociation and drug release in the presence of acid or phosphodiesterase I (PDE I). Moreover, with the comparison of the in vitro antitumor activity for free DOX, the DOX-loaded ACCL micelles, the DOX-loaded ACCL-FA micelles and the DOX-loaded folate-conjugated acid-insensitive cross-linked (CCL-FA) micelles, it could be found that the DOX-loaded ACCL-FA micelles exhibited higher inhibition of the proliferation of KB cells. In addition, these FA-decorated ACCL micelles showed higher cellular uptake than those micelles without the FA moiety, indicating their unique targetability. These folate-conjugated core cross-linked biodegradable micelles are highly promising for targeted cancer chemotherapy.
链接：
//pubs.rsc.org/en/content/articlelanding/2015/py/c5py00023h#!divAbstract
