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Mitochondria and nucleus delivery of active form of 10-hydroxycamptothecin with dual shell to precisely treat colorectal cancer.

Authors
  • Li, Huai-Qiu1
  • Ye, Wei-Liang1
  • Huan, Meng-Lei1
  • Cheng, Ying1
  • Liu, Dao-Zhou1
  • Cui, Han1
  • Liu, Miao1
  • Zhang, Bang-le1
  • Mei, Qi-Bing2
  • Zhou, Si-Yuan1, 2
  • 1 Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, PR China. , (China)
  • 2 Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Fourth Military Medical University, Xi'an 710032, PR China. , (China)
Type
Published Article
Journal
Nanomedicine
Publisher
Future Medicine
Publication Date
Apr 01, 2019
Volume
14
Issue
8
Pages
1011–1032
Identifiers
DOI: 10.2217/nnm-2018-0227
PMID: 30925116
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. HCPT-loaded nanoparticle [email protected]/PLGA-hyd-PEG4k-folic acid (PT/PHF) and [email protected]/PLGA-SS-PEG4k-folic acid (PSF) were prepared by using emulsion-solvent evaporation method. In vitro experimental results indicated [email protected]/PHF and [email protected]/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 [email protected]/PHF and [email protected]/PSF delivered more ring-closed form of HCPT to tumor tissue, which led to strong antitumor activity. [email protected]/PHF and [email protected]/PSF could enhance therapeutic efficacy of HCPT to colorectal cancer.

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