Synthesis, Characterization, Cellular Uptake, and In Vitro Anticancer Activity of Fullerenol-Doxorubicin Conjugates

Abstract

Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents for treating human cancer. However, its clinical use has been limited by DOX-induced cardiotoxicity as well as other side effects. In the present study, we designed and synthesized the fullerenol (FU)-DOX conjugates and folic acid (FA)-grafted FU-DOX conjugates for improving the selectivity and activity of DOX in cancer cells. We further characterized the physicochemical properties and examined the release kinetics, cellular uptake, and in vitro anticancer activities of FU-DOX and FA-FU-DOX. The results showed that FU-DOX and FA-FU-DOX had a mean diameter of <200 nm and a low polydispersity. Both FU-DOX and FA-FU-DOX exhibited pH sensitivity and their DOX release rates were higher at pH 5.9 vs. pH 7.4. The cellular uptake studies indicated that FU conjugation enhanced the intracellular accumulation of DOX in human hepatocellular carcinoma (HCC) cell lines (BEL-7402 and HepG2) and the immortalized normal human hepatocytes (L02). The conjugation of FA to FU-DOX further promoted the drug internalization in an FR-dependent manner and enhanced the cytotoxicity against HCC cells. In conclusion, the newly prepared FA-FU-DOX conjugates can optimize the safety and efficacy profile of DOX.

Long Noncoding RNA AC007639.1 Promotes the Pathogenesis and Progression of Hepatocellular Carcinoma Through Inhibiting Apoptosis and Stimulating Chemotherapeutic Resistance

“…Therefore, to avoid controversies, SMMC-7721 cells were just used to test the efficacy of siRNA knock down ( 19 ), but not selected for further mechanistic experiments. Doxorubicin is among the most used chemotherapeutics against human cancers ( 20 ), the resistance of which is related with lncRNA AC007639.1 as shown in this study.…”

Synthesis and Characterization of Supermagnetic Nanocomposites Coated with Pluronic F127 as a Contrast Agent for Biomedical Applications

“…The cellular uptake of PBS (control), MNP-F127-3, MNP-F127-3-DOX, and free DOX was observed using fluorescence microscopy, as previously reported [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Briefly, a piece of coverslip was placed into each well of 6-well plates, and HepG2 cancerous cells were seeded on top at a cell density of 5 × 10 3 cells/well.…”

Self-Assembled Fullerene Nanostructures for Mimicking and Understanding of Natural Enzymes

“…The attachment of amino acids onto fullerene surfaces was proven by 1 H NMR and elemental analysis techniques (Figures S2–S6 and Table S1). For quantification of the amino acid number on fullerenes, the HPLC-based amino acid quantification method was used (Figures S7–S11) since there is no denotative mass spectrum analysis of fullerenol and its derivatives in the literature. , In this HPLC method, the acid treatment caused the breakage of C–N bonds between amino acids and fullerenols, similar to acid hydrolysis of proteins. Released amino acids were then fluorescently derivatized and quantified (Tables S2 and S3).…”