Abstract
BackgroundCombination therapy using more than one drug can result in a synergetic effect in clinical treatment of cancer. For this, it is important to develop an efficient drug delivery system that can contain multiple drugs and provide high accumulation in tumor tissue. In particular, simultaneous and stable loading of drugs with different chemical properties into a single nanoparticle carrier is a difficult problem.ResultsWe developed rhamnolipid-coated double emulsion nanoparticles containing doxorubicin and erlotinib (RL-NP-DOX-ERL) for efficient drug delivery to tumor tissue and combination chemotherapy. The double emulsion method enabled simultaneous loading of hydrophilic DOX and hydrophobic ERL in the NPs, and biosurfactant RL provided stable surface coating. The resulting NPs showed fast cellular uptake and synergetic tumor cell killing in SCC7 cells. In real-time imaging, they showed high accumulation in SCC7 tumor tissue in mice after intravenous injection. Furthermore, enhanced tumor suppression was observed by RL-NP-DOX-ERL in the same mouse model compared to control groups using free drugs and NPs containing a single drug.ConclusionsThe developed RL-NP-DOX-ERL provided efficient delivery of DOX and ERL to tumor tissue and successful tumor therapy with a synergetic effect. Importantly, this study demonstrated the promising potential of double-emulsion NPs and RL coating for combination therapy.Graphical
Highlights
Despite the extensive amount of time and effort devoted to the fight against cancer over many years, cancer remains a leading cause of death worldwide, with nearly 10 million deaths reported in 2020 [1]
It has been reported that ERL inhibits epidermal growth factor receptor (EGFR) and makes tumor cells more sensitive to nucleotide damage induced by DOX [13]
We reported that rhamnolipid (RL), a biosurfactant originated from Pseudomonas aeruginosa, can a Scheme 1 Schematic illustration of rhamnolipid-coated double-emulsion nanoparticles containing doxorubicin and erlotinib (RL-NP-DOX-ERL) for efficient drug delivery to tumor tissue and combination chemotherapy. a Structure of RL-NP-DOX-ERL formed by W/Oil in water (O/W) double emulsion. b Drug delivery and combinational therapy using RL-NP-DOX-ERL
Summary
Despite the extensive amount of time and effort devoted to the fight against cancer over many years, cancer remains a leading cause of death worldwide, with nearly 10 million deaths reported in 2020 [1]. Some of them were synergetic and resulted in better clinical outcomes, but there were many cases that were less effective [7]. This highlights the importance of finding a synergetic combination of drugs [8]. Doxorubicin (DOX) and erlotinib (ERL) have shown their pronounced synergy in many cases including glioblastoma, hepatocellular carcinoma, non-small cell lung cancer, and triple-negative breast cancer [9,10,11,12]. It has been reported that ERL inhibits epidermal growth factor receptor (EGFR) and makes tumor cells more sensitive to nucleotide damage induced by DOX [13]. Combination therapy using more than one drug can result in a synergetic effect in clinical treatment of cancer. Simultaneous and stable loading of drugs with different chemi‐ cal properties into a single nanoparticle carrier is a difficult problem
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