Abstract
In this paper, the self-assembled folate-biotin-quaternized starch nanoparticles (FBqS NPs) were used as carrier system of doxorubicin (DOX) and siRNAIGF1R for the codelivery of both into human lung adenocarcinoma cell lines (A549 cells) in vitro. The cytotoxicity, targeted ligand competition, cell proliferation inhibition, cellular uptake, endocytosis mechanism and target protein suppression of drug-loaded FBqS NPs were evaluated in detail. Compared with several other drug formulations under same condition, siRNAIGF1R/DOX/FBqS NPs exhibited the greatest cytotoxicity to A549 cells and the cytotoxicity was competitively inhibited by free folate in dose-dependent manner. The A549 cells treated by siRNAIGF1R/DOX/FBqS NPs showed the lowest cell proliferation capacity. The energy-dependent clathrin- and caveolae-mediated endocytosis might be the primary cellular uptake mechanism of drug-loaded FBqS NPs. The expression of IGF1R protein in A549 cells treated by siRNAIGF1R/FBqS NPs declined dramatically. So the FBqS NPs were expected as the co-carrier system of chemotherapeutants and siRNAs for future clinical application.
Highlights
IntroductionThe main tumor treatments, such as surgery, chemotherapy, and radiotherapy, still have some limitations which cripple the therapeutic effect
The double-stranded siRNAIGF1R and FAM-labeled siRNAIGF1R (FAM: carboxyfluorescein) were designed and chemically synthesized by GenePharm Co., Ltd (Shanghai, China). 3-(4,5-Dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation and cytotoxicity assay kit, Annexin V-FITC apoptosis detection kit, Hoechst 33342, 4% paraformaldehyde, folate, biotin, RPMI1640 medium, phosphate-buffered saline (PBS), fetal bovine serum (FBS), bicinchoninic acid (BCA) protein assay kit and polyvinylidene difluoride (PVDF) membrane were provided by Sangon Biotech Co., Ltd (Shanghai, China)
Except for the group of siRNAIGF1R/FBqS NPs, the cytotoxicity of other administration groups enhanced as DOX concentration increased, showing the cytotoxicity was a function of DOX dose
Summary
The main tumor treatments, such as surgery, chemotherapy, and radiotherapy, still have some limitations which cripple the therapeutic effect. Chemotherapy, the most common cancer treatment, is mainly performed through intravenous injection of small molecule anticancer drugs to suppress tumor cells. As the first leading causes of cancer death in China, lung cancer has drawn great concern in recent years (Bica-Pop et al, 2018; Collett et al, 2018; Zhou et al, 2018). The above-untargeted drug distribution and MDR are found in lung cancer chemotherapy, which may lead to low survival rate, high recurrence rate and even therapeutic failure in lung cancer treatment. It is very important and urgent to find out novel approaches to improve the therapeutic effect in lung cancer chemotherapy (Collett et al, 2018; Li, Zhang, et al, 2018; Zhou et al, 2018)
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