Redox-Responsive Alginate Nanogels with Enhanced Anticancer Cytotoxicity

Abstract

Although doxorubicin (Dox) has been widely used in the treatment of different types of cancer, its insufficient cellular uptake and intracellular release is still a limitation. Herein, we report an easy process for the preparation of redox-sensitive nanogels that were shown to be highly efficient in the intracellular delivery of Dox. The nanogels (AG/Cys) were obtained through in situ cross-linking of alginate (AG) using cystamine (Cys) as a cross-linker via a miniemulsion method. Dox was loaded into the AG/Cys nanogels by simply mixing it in aqueous solution with the nanogels, that is, by the establishment of electrostatic interactions between the anionic AG and the cationic Dox. The results demonstrated that the AG/Cys nanogels are cytocompatible, have a high drug encapsulation efficiency (95.2 ± 4.7%), show an in vitro accelerated release of Dox in conditions that mimic the intracellular reductive conditions, and can quickly be taken up by CAL-72 cells (an osteosarcoma cell line), resulting in higher Dox intracellular accumulation and a remarkable cell death extension when compared with free Dox. The developed nanogels can be used as a tool to overcome the problem of Dox resistance in anticancer treatments and possibly be used for the delivery of other cationic drugs in applications beyond cancer.

Biodegradable Polymer Nanogels for Drug/Nucleic Acid Delivery

“…Cell culture studies indicate that the NGs are quickly taken up by CAL-72 cells (an osteosarcoma cell line), resulting in higher anticancer cytotoxicity when compared to free DOX. 56 3.5.3. Alginate NGs for Targeted Delivery.…”

β-Tricalcium phosphate/poly(glycerol sebacate) scaffolds with robust mechanical property for bone tissue engineering

“…β-TCP/PGS scaffolds without heating and lyophilization treatment (β-TCP/15P-Unc) presented the typical. FTIR spectra of large absorption bands at 1660 and 1390 cm − 1 (asymmetric and symmetric stretching peaks of the carboxylate salt groups) [19]. After heat treatment, the intensity of the peaks was greatly reduced, and the peaks shifted to 1740 cm − 1 , which was associated with the formation of ester linkage (C_O stretching) [15,18].…”

Intracellular Degradable Hydrogel Cubes and Spheres for Anti-Cancer Drug Delivery

“…Moreover, the accumulation of positive charge within the PMAA CS hydrogel particles at pH < 5 can facilitate their endosomal/lysosomal escape via inducing endosomal disruption because of the hydrogel swelling. 5,53,54 After DOX-loading, the (PMAA CS ) 5 multilayer hydrogel particles reversed their surface charge from the negative ζ-potential values of −20 ± 1 and −21.3 ± 0.9 mV to the slightly positive 5.2 ± 0.5 and 3.8 ± 0.4 mV for the cubes and spheres, respectively, as observed from the ζ-potential measurements of the hydrogels at pH = 7.4 (0.01 M phosphate; Figure 4c). This positive surface charge can be attributed to the presence of positively charged DOX molecules (pK a = 8.3) at the hydrogel particle surfaces.…”