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Oral spatial-to-point cascade targeting "sugar-coated bullets" for precise and safe chemotherapy by intervention
Xiudan Wang1, Wen Guo1, Jianan Han1
1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
Abstract:
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.
Insights
This study introduces an oral cancer therapy using sugar-coated nanoparticles to deliver shikonin, an inhibitor of glycolysis, directly to colon cancer cells. This targeted approach effectively halts tumor growth by disrupting cancer cell energy metabolism.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Glycolysis is crucial for tumor growth and progression.
- Targeting cancer cell metabolism, specifically the Warburg effect, is a promising therapeutic strategy.
- Developing safe and effective oral drug delivery systems for cancer treatment remains a challenge.
Purpose of the Study:
- To design and evaluate an oral nanocarrier system for targeted delivery of shikonin (SHK) to colon cancer cells.
- To exploit the Warburg effect for cancer therapy through a novel cascade targeting strategy.
- To enhance the solubility and drug-loading capacity of shikonin.
Main Methods:
- Colloidal mesoporous silica nanoparticles (CMS) were loaded with shikonin (SHK).
- CMS/SHK nanoparticles were coated with dextran to form DCMS/SHK, creating a "sugar-coated bullet".
- The system utilized a spatial-to-point cascade targeting approach, leveraging colon-specific dextranase for glucose release and subsequent tumor cell endocytosis.
Main Results:
- The CMS structure enhanced SHK solubility and drug-loading capacity.
- The dextran coating facilitated colon-specific release and glucose-mediated tumor cell uptake.
- The delivered SHK effectively inhibited cancer cell glycolysis and suppressed tumor growth.
Conclusions:
- The developed DCMS/SHK system presents an innovative oral colon-targeting strategy for cancer therapy.
- This approach successfully disrupts cancer cell energy metabolism by targeting glycolysis.
- The study highlights the potential of nanomedicine in developing effective and targeted cancer treatments.
