Background
This study investigated the use of nanodiamond particles (NDs) as a promising material for drug delivery in vivo and in vitro.
Methods
HepG2 cells (a human hepatic carcinoma cell line) were used to determine the characteristics of a nanodiamond-doxorubicin complex (ND-DOX) when taken up by cells in vitro using laser scanning confocal microscopy and dialysis experiments. We also compared the survival rate and histopathology of tumor-bearing mice after treatment with NDs or ND-DOX in vivo.
Results
In vitro investigation showed that ND-DOX has slow and sustained drug release characteristics compared with free doxorubicin. In vivo, the survival rate of tumor-bearing mice treated with ND-DOX was four times greater than that of mice treated with free doxorubicin. Interestingly, the survival rate in mice treated with NDs alone was close to that of mice treated with free doxorubicin. This indicates that treatment with ND-DOX can prolong the lifespan of tumor-bearing mice significantly compared with conventional doxorubicin and that NDs can have this effect as well. Histopathological analysis showed that neither the NDs nor ND-DOX were toxic to the kidney, liver, or spleen in contrast with the well-known toxic effects of free doxorubicin on the kidney and liver. Further, both the bare NDs and ND-DOX could suppress tumor growth effectively.
Conclusion
NDs can potentially prolong survival, and ND-DOX may act as a nanodrug with promising chemotherapeutic efficacy and safety.
An effective drug delivery system based on functionalized nanodiamond (ND) is constructed by layer-bylayer synthesis. Initially, ND is modified with PEG-diamine and conjugated with folate (FA) to obtain a ND-PEG-FA (NPF) nanocarrier. Then, doxorubicin (DOX) is physically attached to the NPF nanocarriers to prepare the drug system (ND-PEG-FA/DOX, NPFD), which exhibits excellent stability under neutral pH conditions, and releases large amounts of DOX in acidic extracellular fluids (pH 6.5 or pH 5.5). Relying on the role of folate and folate receptors, NPFD nanoparticles tend to discriminate between tumor cells and normal cells and enter the cells by clathrin-dependent and receptor-mediated endocytosis. Interestingly, an MTT assay found that the NPFD nanoparticles not only demonstrated a slow and sustained drug release profile, but also had tumor-targeted toxicity. This implies that the NPFD system is capable of targeted drug delivery and can act as a nanodrug with promising chemotherapeutic efficacy and safety.
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