SYL3C aptamer-anchored microemulsion co-loading β-elemene and PTX enhances the treatment of colorectal cancer

Drug Delivery

Nan Li¹  Xiaorong Zhou¹  Shaofei Yuan²  Chuanpei Cao³ 

[1] Department of Medicine, Jiangsu Cancer Hospital, Nanjing, People’s Republic of China;Department of Medicine, Jiangsu Cancer Hospital, Nanjing, People’s Republic of China;Department of Medical Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of Chin;Gastrointestinal Surgery, Affiliated Hospital of Jiujiang University, Jiujiang, People’s Republic of China;

关键词: PTX;    β-elemene;    colorectal cancer;    AS1411 aptamer;    EpCAM;   

DOI  :  10.1080/10717544.2019.1660733

来源: publisher

【 摘 要 】

The aim of this study is to construct a SYL3C aptamer-anchored microemulsion based on β-elemene and PTX (SYL3C/EP-MEs) for enhancement on colorectal cancer therapy. Such microemulsion is consist of encapsulated drugs (β-elemene and PTX), tumor targeting ligand (3’-end thiolated SYL3C aptamer), thiol conjugated site (maleimide-modified PEGylated 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, mal-DOPE-PEG), pH-sensitive component (DOPE) and other necessary excipients. SYL3C/EP-MEs showed a spherical particle with an average particle size around 30 nm and a high encapsulation efficiency (>80%) for both drugs. β-elemene and PTX could be released controllably from SYL3C/EP-MEs as pH values changed. SYL3C/EP-MEs displayed a selective affinity to HT-29 cells, leading to an obvious increase in cellular uptake, cell apoptosis and cytotoxicity. In the HT-29 tumor xenograft-bearing nude mice model studies, SYL3C/EP-MEs showed an overwhelming tumor growth inhibition, the longest survival time and the lowest systemic toxicity among all the treatments. The potential mechanism of enhanced anti-cancer ability was probably associated with the induction of M1 macrophage polarization, the downregulation of mutant p53 protein and the reduction of bcl-2 protein expression. Collectively, the microemulsion codelivery of β-elemene and PTX using functionalization with SYL3C aptamer provides a novel approach for combinational colorectal cancer-targeted treatment.

【 授权许可】

CC BY