Journal
FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.720777
Keywords
chloroquine phosphate; lipid nanoparticles; colorectal cancer; liver metastasis; ROS; dihydroartemisinin
Categories
Funding
- National Natural Science Foundation of China [81960647, 81702833]
- Guizhou Provincial Natural Science Foundation [(2019)1255]
- Excellent Young Talents Plan of Guizhou Medical University [2020-102, 2021-103]
- High-level Overseas Talent Fund for Home Work from the Ministry of Human Resources and Social Security [RSBLXHGZ202001]
- Foundation for Training Programs of Innovation and Entrepreneurship for Undergraduates of Guizhou Medical University [S202010660037]
- Jiangsu Provincial Special Program of Medical Science [BE2019617]
- Distinguished Young Scholars of Nanjing [JQX20008]
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An optimized nanoplatform for DHA and CQ combination therapy against colorectal cancer was developed in this study, showing potential efficacy in inhibiting proliferation and metastasis of tumor cells.
Antimalarial drugs Dihydroartemisinin (DHA) and chloroquine phosphate (CQ) exhibit evident anti-cancer activity, particularly as combination therapy. DHA and CQ combination therapy has been proved to exhibit higher cytotoxic effect in tumor cells and lower toxicity to normal cells than combination of artemisinin derivatives (ARTs) and anticancer chemotherapy drugs. However, different physiochemical properties of DHA and CQ, leading to distinctive in vivo outcomes, considerably limited their synergistic effect in cancer treatment. Herein, we developed a lipid nanoparticle (LNP) for co-delivery of DHA and CQ to inhibit proliferation and metastasis of colorectal cancer. Considering the beneficial effects of acid/reactive oxide species (ROS)-sensitive phospholipids and targeting ligands for colorectal cancer cells, an RGD peptide-modified pH/ROS dual-sensitive LNP loaded with DHA and CQ (RLNP/DC) was prepared. It exhibited optimal cytotoxicity and suppression of invasion and metastasis in HCT116 cells in vitro, attributable to irreversible upregulation of intracellular ROS levels, downregulation of VEGF expression, and upregulation of paxillin expression. A mouse model of orthotopic metastasis of colorectal cancer was established to evaluate anti-proliferation and anti-metastasis effects of RLNP/DC in vivo. Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.
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