期刊
EXPERT OPINION ON DRUG DELIVERY
卷 19, 期 6, 页码 743-754出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2022.2083602
关键词
Nano coordination polymer; theranostics; doxorubicin; breast cancer; dithiodiglycolic acid; magnetic resonance imaging; AS1411 aptamer
资金
- Mashhad University of Medical Sciences [981365]
In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized for the treatment of breast cancer. The developed intelligent platform demonstrated high drug loading capacity, pH and redox-responsive drug release, and showed outstanding therapeutic and diagnostic capabilities against breast cancer.
Background Nanoscale coordination polymers (nCP) have exhibited a great potential in designing of the theranostic platforms in the latest years. However, they have low selectivity for cancerous tissues and require to be modified for becoming effective cancer therapeutics. In this study, a novel nanoscale pH and redox-responsive coordination polymer with high selectivity was synthesized. Methods The nCP was synthesized by iron(III) chloride and dithiodiglycolic acid. After loading the prepared nCP with doxorubicin (DOX), nCP was coated with an amphiphilic copolymer composed of alpha-tocopheryl succinate-polyethylene glycol (VEP). Next, AS1411 aptamer was decorated on the VEP shell of the DOX-loaded nCP (Apt-VEP-nCP@DOX) to provide a guided drug delivery platform. Results The prepared platform demonstrated high DOX loading capacity and pH and redox-responsive DOX release. Apt-VEP-nCP@DOX displayed greater DOX internalization and toxicity toward breast cancer cells of 4T1 and MCF7 compared with that of non-targeted VEP-nCP@DOX. Also, the intravenous injection of Apt-VEP-nCP@DOX (a single dose) considerably suppressed the 4T1 tumor growth in vivo. Moreover, Apt-VEP-nCP@DOX showed outstanding magnetic resonance (MR) imaging capability for 4T1 adenocarcinoma diagnosis in ectopic 4T1 tumor model in mice. Conclusions The developed innovative intelligent Apt-VEP-nCP@DOX could serve as a safe and biocompatible theranostic platform appropriate for further translational purposes against breast cancer.
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