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Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
A Novel Doxorubicin Prodrug with GRP78 Recognition and Nucleus-Targeting Ability for Safe and Effective Cancer
Guo-Bin Ding1,2, Junqing Sun1,2, Peng Yang1,2
1Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University , Taiyuan 030006, China.
Abstract:
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.
Insights
A novel doxorubicin prodrug targets GRP78 and cancer cell nuclei for improved colorectal cancer therapy. This GRP78-targeting drug shows enhanced efficacy and safety in preclinical models.
Area of Science:
- Oncology
- Drug Delivery
- Molecular Biology
Background:
- Glucose-regulated protein of 78 kDa (GRP78) is a novel target for cancer therapy.
- Efficiently delivering chemotherapy drugs like doxorubicin (DOX) to tumor cell nuclei is crucial for effective treatment and reduced side effects.
Purpose of the Study:
- To synthesize a novel doxorubicin prodrug (NDP) with GRP78 recognition and nucleus-targeting capabilities.
- To evaluate the antiproliferative activity, cellular uptake, and in vivo efficacy of the NDP against colorectal cancer.
Main Methods:
- Facile chemical synthesis of a novel doxorubicin prodrug (NDP).
- Assessment of NDP's antiproliferative activity against colorectal cancer cells in vitro.
- Evaluation of NDP's nucleus-targeting ability and cellular uptake.
- Testing the efficacy and safety of NDP against colorectal cancer xenografts in nude mice.
Main Results:
- The synthesized NDP demonstrated enhanced antiproliferative activity against colorectal cancer cells.
- NDP efficiently entered the cell nucleus.
- NDP showed significantly stronger inhibition of colorectal cancer xenograft growth compared to free DOX.
- NDP exhibited superior in vivo safety profiles.
Conclusions:
- The study presents a novel GRP78 and nucleus-targeting strategy for drug delivery.
- The developed NDP holds promise as a potent and safe chemotherapeutic agent for colorectal cancer treatment.
