期刊
MOLECULAR PHARMACEUTICS
卷 15, 期 1, 页码 238-246出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00830
关键词
GRP78; bifunctional peptide; nucleus targeting; novel doxorubicin prodrug; antitumor efficacy
资金
- National Natural Science Foundation of China [31500771]
- Scientific and Technologial Innovation Programs of Higher Education Institutions in Shanxi Province (STIP) [2015116]
- Shanxi Scholarship Council of China [2015-2]
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.
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