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

In this paper, a new nanosuspensions, hydroxycamptothecin (HCPT) and quercetin (QUR) hybrid nanosuspensions (HQ-NPs), was constructed by intermolecular force in the process of microprecipitation. HQ-NPs showed a unique shape, changed crystalline and different dissolution rates compared with HCPT-NPs and QUR-NPs in vitro. We found that HQ-NPs can significantly enhance the accumulation of HCPT in tumor sites (reversing tumor drug resistance), improve the antitumor activity of HCPT, and protect the immune organs and other normal tissues (reducing toxicity), compared with HCPT-NPs. Therefore, hybrid nanosuspensions offer promising potential as the drug delivery system for HCPT and QUR to increase the therapeutic efficacy and reduce the toxicity of HCPT. [Display omitted] 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