Reduction‐Triggered Doxorubicin Delivery by Self‐Assembled Nanospheres of Lipoylated Caffeine

Abstract

This study reports a new amphiphilic bioconjugate (CAFF‐LA) derived from the lipoylation of a hydroxyethyl derivative of caffeine. In water, CAFF‐LA self‐assembles into nanospheres with an average size of 155 nm, as evidenced from dynamic light scattering and electron microscopy studies. The nanospheres are stable in serum and could be disintegrated upon exposure to the reducing environment of dithiothreitol (DTT; 10 mM) and glutathione (GSH; 10 mM). These nanospheres easily encapsulate the chemotherapy medication, doxorubicin (DOX), and demonstrate an efficacious transport into doxorubicin‐resistant cervical cancer (HeLa) cells, wherein a marked induction in apoptosis and significantly lower IC50 have been observed when compared to that of free drug. The in vitro assessment of cell viability and hemocompatibility present these nanospheres as potentially safe and efficient intracellular reduction stimulus‐responsive drug‐delivery vehicles.

Caffeine and Cationic Copolymers with Antimicrobial Properties

“…To investigate the antibacterial properties of caffeine copolymers with hydrophilic charged groups, we prepared libraries of random copolymers through free-radical polymerization. Caffeine polymer derivatives are known to be accessible by free radical polymerization through methacrylate functionalization at the 8-position or 7-position of the caffeine heterocycle or by polymerization of lipoylated caffeine . In the current study, we used etofylline, a derivative of caffeine bearing an ethyl alcohol side chain at the 7-position and functionalized with a methacrylate (Caf-MA) by nucleophilic substitution of methacryloyl chloride in a 56% yield (Figures S1 and S2).…”

“…Caffeine polymer derivatives are known to be accessible by free radical polymerization through methacrylate functionalization at the 8-position 42 or 7-position 43 of the caffeine heterocycle or by polymerization of lipoylated caffeine. 44 In the current study, we used etofylline, a derivative of caffeine bearing an ethyl alcohol side chain at the 7-position and functionalized with a methacrylate (Caf-MA) by nucleophilic substitution of methacryloyl chloride in a 56% yield (Figures S1 and S2). Free-radical homopolymerization of Caf-MA (30 equiv) was performed using azobis(isobutyronitrile) (AIBN, 1 equiv) in dimethyl sulfoxide (DMSO) under argon at 75 °C.…”

Construction of Glycogen-Based Nanoparticles Loaded with Resveratrol for the Alleviation of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease

“…Figure G,I shows that the fluorescence intensity of the GSH-treated group was higher than that of the non-GSH-treated group, especially the Res NPs + GSH group (70.74 ± 0.78). This indicated that after the endocytosis of the NPs, the disulfide bond was destroyed under the redox stimulation, and the drug was released in the cell, which led to a higher accumulation of the drug in the cell . Therefore, these targeted NPs showed promising therapeutic effects, especially those drugs lacking therapeutic targets.…”

“…This indicated that after the endocytosis of the NPs, the disulfide bond was destroyed under the redox stimulation, and the drug was released in the cell, which led to a higher accumulation of the drug in the cell. 52 Therefore, these targeted NPs showed promising therapeutic effects, especially those drugs lacking therapeutic targets. 3.7.…”