Targeted Lipid Nanoparticles Encapsulating Dihydroartemisinin and Chloroquine Phosphate for Suppressing the Proliferation and Liver Metastasis of Colorectal Cancer.
Jianqing Peng, Qin Wang, Jia Zhou, Shuli Zhao, Pan Di, Yan Chen, Ling Tao, Qianming Du, Xiangchun Shen, Yi Chen
Author Information
Jianqing Peng: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Qin Wang: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Jia Zhou: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Shuli Zhao: General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Pan Di: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Yan Chen: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Ling Tao: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Qianming Du: General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Xiangchun Shen: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Yi Chen: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
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 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 , 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 . Thus, an optimized nanoplatform for DHA and CQ combination therapy was developed in this study that offered potential antitumor efficacy against colorectal cancer.
