Abstract
The therapeutic potential of plumbagin, a naphthoquinone extracted from the officinal leadwort with anticancer properties, is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use in clinic is further limited by its poor aqueous solubility, its spontaneous sublimation, and its rapid elimination in vivo. We hypothesize that the entrapment of plumbagin within liposomes grafted with transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumours after intravenous administration. The objectives of this study were therefore to prepare and characterize transferrin‐targeted liposomes entrapping plumbagin and to evaluate their therapeutic efficacy in vitro and in vivo. The entrapment of plumbagin in transferrin‐bearing liposomes led to an increase in plumbagin uptake by cancer cells and improved antiproliferative efficacy and apoptosis activity in B16‐F10, A431, and T98G cell lines compared with that observed with the drug solution. In vivo, the intravenous injection of transferrin‐bearing liposomes entrapping plumbagin led to tumour suppression for 10% of B16‐F10 tumours and tumour regression for a further 10% of the tumours. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any signs of toxicity. Transferrin‐bearing liposomes entrapping plumbagin are therefore highly promising therapeutic systems that should be further optimized as a therapeutic tool for cancer treatment.
Highlights
Cancer, the second leading cause of death in the world, accounted for 9.6 million deaths in 2018 and continues rising worldwide, with an estimation of 16.4 million deaths in 2040 (Bray et al, 2018)
All the tumours treated with plumbagin solution, blank liposomes, or left untreated were progressive
We hypothesized that loading plumbagin into a tumour-targeted delivery system would enhance the specific delivery of plumbagin to cancer cells and increase the therapeutic efficacy both in vitro and in vivo, while at the same time reducing the secondary effects to healthy tissues
Summary
The second leading cause of death in the world, accounted for 9.6 million deaths in 2018 and continues rising worldwide, with an estimation of 16.4 million deaths in 2040 (Bray et al, 2018). Several therapeutic strategies, such as surgery, radiotherapy, and immunotherapy, can be efficacious against cancers, chemotherapy remains an important treatment for patients diagnosed with cancer (Palumbo et al, 2013). Among the current anticancer drugs approved from the late 1930s to 2014, approximately 55% were derived from natural sources (Newman & Cragg, 2016). Example, paclitaxel (from the Pacific yew tree), doxorubicin (from Streptomyces peucetius bacterium), vincristine (from the periwinkle plant), topotecan (from the Camptotheca acuminate tree), and etoposide (from the mayapple plant Podophyllum peltatum) are wellestablished drugs available in the market for cancer treatment. Several natural-derived compounds, such as isoflavones (from soy bean), curcumin oils (from turmeric), and resveratrol (from grape seed) are currently being investigated in clinical trials (Cragg & Pezzuto, 2016). Natural products are an important channel for the discovery of new anticancer agents
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
