An Investigation of In Vitro Anti-Cancer Efficacy of Dihydroartemisinin-Loaded Bovine Milk Exosomes Against Triple-Negative Breast Cancer

• Published in: The AAPS journal Vol. 26; no. 5; p. 91
• Main Authors: Kumar, Dulla Naveen, Chaudhuri, Aiswarya, Shiromani, Udita, Kumar, Dinesh, Agrawal, Ashish Kumar
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 06.08.2024; Springer
• Subjects: Analysis; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Artemisinins - administration & dosage; Artemisinins - chemistry; Artemisinins - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Breast cancer; Cancer; Care and treatment; Cattle; Cell Line, Tumor; Cell Survival - drug effects; Drug approval; Exosomes; Female; Humans; Malaria; Membrane Potential, Mitochondrial - drug effects; Milk - chemistry; Pharmacology/Toxicology; Pharmacy; Reactive Oxygen Species - metabolism; Research Article; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; bovine milk exosomes; cancer; drug delivery; Triple Negative Breast Cancer (TNBC); dihydroartemisinin
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-024-00958-y

Repurposing drugs offers several advantages, including reduced time and cost compared to developing new drugs from scratch. It leverages existing knowledge about drug safety, dosage, and pharmacokinetics, expediting the process of clinical trials and regulatory approval. Dihydroartemisinin (DHA) is a semi-synthetic and active metabolite of all artemisinin molecules and is FDA-approved for the treatment of malaria. Apart from having anti-malarial properties, DHA also possesses anticancer properties. However, its pharmacological actions are limited by toxicity and solubility problems. To overcome these challenges and enhance its anticancer effectiveness, we designed an exosomal formulation of DHA. We isolated exosomes from bovine milk using differential ultracentrifugation and loaded DHA using sonication. Scanning and transition electron microscopy revealed a size of roughly 100 nm, with a spherical shape. Furthermore, in pH 7.4 and 5.5, the exosomes exhibited burst release followed by sustained release. Multiple in vitro cell culture tests demonstrated that Exo-DHA exhibited enhanced anticancer activity, including cytotoxicity, cellular uptake, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, and inhibition of colony formation. Additional evidence supporting Exo-DHA's anti-migration ability came from transwell migration and scratch assays. Based on these results, it was concluded that the anticancer efficacy of DHA was improved when loaded into bovine milk-derived exosomes. While the in vitro results are encouraging, more in vivo testing in suitable animal models and biochemical marker analysis are warranted. Graphical Abstract