Abstract
Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). LV@MSN–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the LV@MSN–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.
Highlights
Colorectal cancer (CRC) is the fourth most frequent cause of cancer-related mortality in China [1].Classical clinical treatments for this condition include surgery, radiotherapy, and most commonly, chemotherapy
A series of characterizations confirmed that the constructed had a mesoporous and that structure and that the successfully covered the surface of mesoporous silica nanoparticles (MSNs)–COOH/galactosylated chitosan (GC)
Release studies showed that the release of LVthat in LV@MSN–COOH/GC
Summary
Colorectal cancer (CRC) is the fourth most frequent cause of cancer-related mortality in China [1]. Due to its unstable oral bioavailability and rapid metabolism by dihydropyrimidine dehydrogenase after oral administration, calcium leucovorin (LV) is usually administered intravenously or via bolus injection, and the combination of 5-FU and LV has become the first-line treatment for colon cancer chemotherapy worldwide [2,3]. It can significantly improve overall survival compared with 5-FU treatment alone [8,9]. On galactosylated chitosan (LV@MSN–COOH/GC) and its mechanism of drug release in SW620 cells
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