Oral spatial-to-point cascade targeting “sugar-coated bullets” for precise and safe chemotherapy by intervention Warburg effect

• DOI: 10.1016/j.colsurfb.2022.113108
• Publication Date: 2022-12-17T15:57:27Z
• Authors: Xiudan Wang; Wen Guo; Jianan Han; Jia Li; Qinfu Zhao; Yuling Mao; Siling Wang
• Keywords: 0303 health sciences; 03 medical and health sciences; Drug Delivery Systems; Glucose; Cell Line, Tumor; Colonic Neoplasms; Humans; Nanoparticles; Dextrans; Sugars; 3. Good health

Glycolysis plays a vital role in the development and progression of tumors. Inhibiting glycolysis via smart and safe methods serves as a promising target for cancer therapy. Here, an oral "sugar-coated bullet" aiming at intervening Warburg effect is designed by coating colloidal mesoporous silica nanoparticles (CMS) encapsulating glycolysis inhibitor shikonin (SHK) with dextran, namely DCMS/SHK. The solubility and drug-loading capacity of SHK were enhanced by the special structure of CMS. Besides, the tempting bullets possess the spatial-to-point cascade targeting ability in delivering SHK from the colonic lumen to colon cancer cells and finally to PKM2. After DCMS/SHK reaches the colon, the dextran is hydrolyzed by dextranase especially existing in the colon site to glucose and the carriers become glucose-coated nanoparticles. The glucose-cloak nanoparticles would be largely endocytosed by tumor cells and complete the efficient delivery of SHK. The encapsulated SHK can prevent the glycolysis of cancer cells and thus inhibit tumor growth effectively. This work presents an ingenious cascade colon-targeting strategy to treat colon cancer by destroying cell energy metabolism.