A Novel Doxorubicin Prodrug with GRP78 Recognition and Nucleus-Targeting Ability for Safe and Effective Cancer Therapy.
Guo-Bin DingJunqing SunPeng YangBin-Chun LiYing GaoZhuoyu LiPublished in: Molecular pharmaceutics (2017)
Glucose-regulated protein of 78 kDa (GRP78) has become an attractive and novel target for tumor therapy. Design and construction of powerful delivery systems that could efficiently transport doxorubicin (DOX) to a tumor-cell nucleus remains a formidable challenge for improving the tumor therapeutic index and mitigating side effects to normal tissues. Herein, a novel doxorubicin prodrug (NDP) with GRP78 recognition and nucleus-targeting ability was synthesized by a facile chemical route. NDP exhibited an enhanced antiproliferative activity against colorectal cancer cells and could efficiently enter the cell nucleus. Furthermore, it is inspiring to note that NDP displayed a much stronger inhibitory efficacy against the growth of colorectal cancer xenografts in nude mice than free DOX and showed superior in vivo safety. Together, the work provides a novel GRP78 and nucleus-targeting strategy, and the NDP holds great promise to be used as a potent and safe chemotherapeutic agent.
Keyphrases
- cancer therapy
- drug delivery
- endoplasmic reticulum stress
- single cell
- cell surface
- cell therapy
- gene expression
- type diabetes
- stem cells
- blood pressure
- mesenchymal stem cells
- insulin resistance
- bone marrow
- adipose tissue
- quantum dots
- amino acid
- high fat diet induced
- anti inflammatory
- reduced graphene oxide
- weight loss
- binding protein
- smoking cessation