Combined nanosuspensions from two natural active ingredients for cancer therapy with reduced side effects

Tumor drug resistance and systemic side effects of chemotherapeutic drugs are the main reasons for the failure of cancer treatment. In recent years, it was found that some natural active ingredients can reverse MDR and regulate body immunity to enhance the efficacy and reduce toxicity of chemotherapeutic drugs. In this paper, a new nanosuspensions, HCPT and QUR hybrid nanosuspensions (HQ-NPs), was prepared by the microprecipitation-high pressure homogenization method to reverse tumor drug resistance, reduce toxicity, and increase therapeutic efficacy. The in vitro investigation results showed that HQ-NPs had a unique shape (particle size was about 216.3 +/- 5.9 nm), changed crystalline, and different dissolution rates compared with HCPT-NPs and QUR-NPs, which is attributed to the strong intermolecular forces between HCPT and QUR as indicated by the results of the molecule dock. It was verified that the HQ-NPs could double the retention of HCPT in cells and enhance the cytotoxicity to A549/PTX cells in vitro tests compared with HCPT-NPs. We also found that HQ-NPs can significantly enhance the accumulation of HCPT in tumor sites, improve the antitumor activity of HCPT, and protect the immune organs and other normal tissues (P < 0.01), compared with HCPT-NPs. Therefore, hybrid nanosuspensions can offer promising potential as the drug delivery system for HCPT and QUR to increase the therapeutic efficacy and reduce the toxicity of HCPT. (C) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

The hybrid nanosuspensions of HCPT and QUR have shown promising potential in reversing tumor drug resistance, enhancing therapeutic efficacy, reducing toxicity, and significantly increasing HCPT accumulation at tumor sites. Additionally, these nanosuspensions can enhance cytotoxicity to cancer cells and protect immune organs and normal tissues, making them a potential drug delivery system for improving cancer treatment.