1. Mitochondria and nucleus delivery of active form of 10-hydroxycamptothecin with dual shell to precisely treat colorectal cancer.
- Author
-
Li HQ, Ye WL, Huan ML, Cheng Y, Liu DZ, Cui H, Liu M, Zhang BL, Mei QB, and Zhou SY
- Subjects
- Animals, Antineoplastic Agents, Phytogenic pharmacology, Biological Transport, Camptothecin pharmacology, Caspase 3 metabolism, Cell Line, Tumor, Cell Survival drug effects, Drug Liberation, Emulsions chemistry, Folic Acid chemistry, Folic Acid metabolism, Humans, Mice, Mice, Nude, Models, Animal, Nanoparticles chemistry, Particle Size, Polyesters chemistry, Polyethylene Glycols chemistry, Surface Properties, Tissue Distribution, Camptothecin analogs & derivatives, Cell Nucleus metabolism, Colorectal Neoplasms drug therapy, Drug Carriers chemistry, Mitochondria metabolism
- Abstract
Aim: The objective of this study was to deliver a ring-closed form of 10-hydroxycamptothecin (HCPT) to the mitochondria and nucleus to treat colorectal cancer., Materials & Methods: HCPT-loaded nanoparticle HCPT@PLGA-PEG
2k -triphenylphosphonium/PLGA-hyd-PEG4k -folic acid (PT/PHF) and HCPT@PT/PLGA-SS-PEG4k -folic acid (PSF) were prepared by using emulsion-solvent evaporation method., Results: In vitro experimental results indicated HCPT@PT/PHF and HCPT@PT/PSF maintained a large amount of HCPT in active form, and delivered more HCPT to the nucleus and mitochondria of the tumor cell, which resulted in the enhancement of cytotoxicity of HCPT. In vivo experimental results indicated that HCPT@PT/PHF and HCPT@PT/PSF delivered more ring-closed form of HCPT to tumor tissue, which led to strong antitumor activity., Conclusion: HCPT@PT/PHF and HCPT@PT/PSF could enhance therapeutic efficacy of HCPT to colorectal cancer.- Published
- 2019
- Full Text
- View/download PDF