Abstract
Nanomaterials-based drug delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention effect and diversified chemical modification. In this study, we have tailored and synthesized different sized mesoporous silica nanoparticles (MSNs) through reactant control to investigate the relevancy of nanoparticle size toward anticancer efficacy and suppressing cancer multidrug resistance. The different sized MSNs loaded with anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs) can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs exhibit higher anticancer activity against HepG2 cells, while the larger sized (80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS overproduction in cancer cells, leading to DNA damage and p53 phosphorylation, consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious toxicity in major organs of tumor-bearing nude mice. Taken together, these results verify the size effects of MSNs nanosystem for precise cancer therapy.
Highlights
Nanotechnology-based delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention (EPR) effect of nanoparticles (Talelli et al, 2015; Yu & Zheng, 2015)
Nanoparticles with EPR effect permeate into tumor sites from its leaky epithelium and discontinuous microvasculatures, which formed by the rapid growth of tumors (Peer et al, 2007)
For example under the same condition with 0.3 vt% TEA as base catalyst and 0.75 vt% tetraethyl orthosilicate (TEOS) as silica source, mesoporous silica nanoparticles (MSNs) at 60 or 80 nm was obtained with 10 wt% cetyltrimethylammonium bromide (CTAB) or cetyltrimethylammonium chloride (CTAC) as templates, respectively
Summary
Nanotechnology-based delivery systems display potent applications in cancer therapy, owing to the enhanced permeability and retention (EPR) effect of nanoparticles (Talelli et al, 2015; Yu & Zheng, 2015). Many different nanomaterials have been reported as drug carriers for cancer therapy, such as selenium nanoparticles, liposomal, oxides, proteins, and polymers (Shen et al, 2014; Huang et al, 2016; Song et al, 2016; Shi et al, 2017). Among these nanomaterials, mesoporous silica nanoparticle (MSN) provide superior drug delivery system options because of high drug loading capability, high biocompatibility, low toxicity, especially the controllable particle size and pore size (He et al, 2014a; Jiang et al, 2014; Hu et al, 2015; Chen & Shi, 2016). Polypeptide and folate acid (FA) that can preferentially recognize tumor cell surface biomarkers and enhance selectivity
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