The solvent stability of bromovirus allows for delivery of hydrophobic chemotherapeutic drugs

Abstract

Breast cancer is one of the main causes of mortality in women, and chemotherapy remains a fundamental pillar in its treatment. Although chemotherapy remains a mainstay in the treatment of breast cancer, the hydrophobicity and instability of drugs such as camptothecin (CPT) hinder their administration and bioavailability in aqueous media. To improve their solubility and stability, it is necessary to use suitable solvents that allow their encapsulation in nanovehicles without compromising their functionality. In this study, the use of viral nanoparticles (VNPs) derived from brome mosaic virus (BMV) and cowpea chlorotic mottle virus (CCMV) as platforms for the controlled delivery of CPT was investigated, evaluating the stability of the bromovirus in different polar solvents (methanol, ethanol, isopropanol, and DMSO). It was found that the viruses remain stable up to a concentration of 50% in all solvents, for at least one week except in ethanol and isopropanol, where stability is maintained up to 30%. DMSO proved to be the optimal solvent, as it preserved their size and, in addition, favored trapping CPT in VNPs. Drug entrapment was more efficient in BMV, with a 30% higher uptake compared to CCMV when DMSO-PBS was used. In silico analysis using Autodock Vina revealed that drug retention occurs through hydrophobic interactions and hydrogen bonds between viral CP and camptothecin. The computationally predicted amount of drug entrapped in virions agrees with experimental results. In vitro studies in MDA-MB-231 cells confirmed the internalization of this bromovirus VNPs in the cell nucleus and a 50% higher cytotoxicity compared to free CPT. These findings highlight the potential of plant VNPs as an innovative platform for the enhanced delivery of hydrophobic drugs in the treatment of tiple negative breast cancer.