Assembly of folate-carbon dots in GdDy-doped layered double hydroxides for targeted delivery of doxorubicin

Abstract Layered double hydroxides (LDH) have been extensively studied as drug delivery systems. In this work we doped LDH with dysprosium and gadolinium (GdDy-LDH). The resulting nanoparticles showed a higher contrast effect in magnetic resonance imagining (MRI) than a commercial reference from the inclusion of Gd3+ and Dy3+ cations into the LDH structure, presenting r1 = 3.49 1/mM s and r2 = 18.17 1/mM s. Additionally, GdDy-LDH was assembled to doxorubicin (DOX) and folate‑carbon dots (folate-CDs) as an approach to design cancer-targeted therapeutic agents. Carbon dots were produced strategically by reacting folic acid and lysine, resulting in a surface of carbon functionalized with amino groups from lysine and folate residues. CDs emitted a maximal fluorescence at 515 nm when excited with blue light at 420 nm. The cytotoxicity was evaluated with HeLa cancer cells, which overexpress the folate receptor. The low cytotoxicity of GdDy-LDH and folate-CDs on HeLa cells indicated their promising use as a potential carrier. Folate-CDs/DOX/GdDy-LDH exhibited a half-maximal inhibitory concentration of 0.16 μg/mL, which is lower than that of DOX itself (1.16 μg/mL) or DOX/GdDy-LDH (0.9 μg/mL). The loading of DOX in the folate-CDs/DOX/GdDy-LDH nanocomposites lead to strong inhibition of cell proliferation, possibly, due to a more efficient internalization promoted by electrostatic interaction with the amino groups from lysine and endocytosis mediated by the folate receptor.