Cyclodextrin based unimolecular micelles with targeting and biocleavable abilities as chemotherapeutic carrier to overcome drug resistance

Publication date: December 2019Source: Materials Science and Engineering: C, Volume 105Author(s): Wenqiang Li, Chenfang Xu, Shuxian Li, Xiuying Chen, Xiaoshan Fan, Zhiguo Hu, Yun-Long Wu, Zibiao LiAbstractAn amphiphilic star-shaped copolymer β-CD-g-PCL-SS-PEG-FA, consisting of a β-cyclodextrin (β-CD) core as well as grafted with bioreducible disulfide linkage in PCL-SS-PEG multiarms and targeting folic acid (FA) as end moiety, is designed with unimolecular micelles formation ability for targeted transport of chemotherapeutics to drug resistant tumor cells. Firstly, β-CD was utilized as core to growth PCL arms by ring-opening polymerization (ROP) of ε-CL, before disulfide terminal group transformation to render β-CD-g-PCL-SS-COOH. Secondly, α-hydroxy-ω-amine protected PEG (HO-PEG-NHBoc) was connected to β-CD-g-PCL-SS-COOH to obtain amphiphilic β-CD-g-PCL-SS-PEG, where PCL and PEG were connected via bioreducible disulfide bond. After deprotection of -Boc group, FA was introduced onto the distal end of block arms to obtain the desired β-CD-g-PCL-SS-PEG-FA copolymer. Because of highly branched core-shell amphiphilic structures, β-CD-g-PCL-SS-PEG-FA could act as unimolecular micelles. Interestingly, this unimolecular micelle could release the encapsulated drug in a glutathione (GSH) dependent manner due to disulfide linkage. More importantly, this unimolecular micelle could load doxorubicin (DOX) to promote its cellular uptake in multidrug resistance (MDR) protein over...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research