Folate-conjugated nanodiamond for tumor-targeted drug delivery

Abstract

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.

Smart pH-responsive and high doxorubicin loading nanodiamond for in vivo selective targeting, imaging, and enhancement of anticancer therapy

“…42 However, the amount of DOX released increased with pH values decreased, at pH 6.5 (a simulated tumor environment), NPDC released about 25 %. When the pH was decreased to 5.0, the released DOX was markedly increased nearly 80 %, which is about twice as high as the previous work, [43][44][45] as it was expected that the NPDC nanoparticles had minimal drug release (under simulated physiological conditions, pH 7.4), but much more DOX were released in acidic endosomes of cells (pH 5.0-5.5). This pH-responsive release property can be chiefly associated with the hydrogen bonds damage between amino of DOX and carboxy of Cit 3-, which is influenced by pH.…”

“…This is due to the presence of spherical doxorubicin. To our knowledge, the nanodiamond carriers for DOX loaded as moleculars were clathrin-mediated process, 18,33,42,43,45 while the NPDC system was found to be both clathrin-and caveolae mediated process, suggesting that there is a link between uptake mechanism and shape of DOX onto the surface of ND. Our finding is in agreement with previous report that chan and their coworkers demonstrated the relation between the mechanism of cellular uptake and different sizes and shapes for nanoparticles.…”

“…43 Then ND-PEG was dispersed in sodium citrate (Na 3 Cit, 1.0 M) medium to sonicate for 1h at room temperature followed by adding DOX and mixed thoroughly. After shaking for 6 h to make the DOX adsorb onto the ND-PEG nanoparticles exhaustively, the solution was centrifuged to remove any non-adsorbed DOX.…”

A Perspective on Fluorescent Nanodiamond Bioimaging

“…Though internalization can be useful for labeling cells, different cell types have variability in uptake rates and this route lacks specificity. A number of targeting ligands have been used to increase uptake and association of FND with specific cell types, including folic acid, [50,51] transferrin, [52] ubiquitin, [53] targeting peptides (TAT and GAG targeting, RGD), [54][55][56][57] and vascular endothelial growth factor. [34] In all such cases, the nature of targeting ligand attachment is an important experimental design parameter.…”

Targeted PD-L1 PLGA/liposomes-mediated luteolin therapy for effective liver cancer cell treatment

“…Programmed death ligand-1 (PD-L1), which is highly expressed on the surface of HCC cells, also associated with poor prognosis of liver cancer. The PD-L1targeting nano-drug delivery system display 8,9 the double advantages of active targeting of the PD-1 and passive targeting of the nanometer delivery system, and it can achieve the targeted delivery of drugs to tumor tissues, thereby improving the efficacy of drugs effectively and reducing side effects.…”