Chemical tumor-targeting of nanoparticles based on metabolic glycoengineering and click chemistry
- Chemical tumor-targeting of nanoparticles based on metabolic glycoengineering and click chemistry
- 이상민; 구희범; 나진희; 한승진; 민현수; 이소진; 김선화; 윤석현; 정서영; 권익찬; 최귀원; 김광명
- nanoparticle; click chemistry; metabolic glycoengineering; tumor targeting; drug delivery
- Issue Date
- ACS Nano
- VOL 8, NO 3, 2048-2063
- Tumor-targeting strategies for nanoparticles have been predominantly based on optimization of physical properties or conjugation with biological ligands. However, their tumor-targeting abilities remain limited and insufficient. Furthermore, traditional biological binding molecules have intrinsic limitations originating from the limited amount of cellular receptors and the heterogeneity of tumor cells. Our two-step in vivo tumor-targeting strategy for nanoparticles is based on metabolic glycoengineering and click chemistry. First, an intravenous injection of precursor-loaded glycol chitosan nanoparticles generates azide groups on tumor tissue specifically by the enhanced permeation and retention (EPR) effect followed by metabolic glycoengineering. These ‘receptor-like’ chemical groups then enhance the tumor-targeting ability of drug-containing nanoparticles by copper-free click chemistry in vivo during a second intravenous injection. The advantage of this protocol over traditional binding molecules is that there are significantly more binding molecules on the surface of most tumor cells regardless of cell type. The subsequent enhanced tumor-targeting ability can significantly enhance the cancer therapeutic efficacy in animal studies.
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