Dual responsive dextran-graft-poly (N-isopropylacrylamide)/doxorubicin prodrug via Schiff base reaction

• Published in: International journal of biological macromolecules 2021-08, Vol.185, p.390-402
• Main Authors: Carneiro, Maria J.M., Paula, Cláudio B.A., Ribeiro, Irisvan S., de Lima, Laís R.M., Ribeiro, Fábio O.S., Silva, Durcilene A., Araújo, Gisele S., Marinho Filho, José D.B., Araújo, Ana J., Freire, Rosemayre S., Feitosa, Judith P.A., de Paula, Regina C.M.
• Format: Article
• Language: English
• Subjects: Cancer; Graft copolymer; pH-sensitive
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2021.06.095

Stimulus-responsive nanoparticles stand out in studies for cancer treatment since these systems can promote a selective release of the drug in tumor tissues and cells, minimizing the effects caused by conventional chemotherapy. Dextran-graft-poly (N-isopropylacrylamide) copolymers were synthesized via Schiff base formation. The synthesis of copolymers was confirmed by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (NMR) and the analyses of dynamic light scattering (DLS) showed that the copolymers were thermal and pH dual-responsive. The chemotherapy drug doxorubicin (DOX) was conjugated to the copolymers via Schiff base formation, obtaining nanoparticles by self-assembling with size smaller than 130 nm. A higher percentage of doxorubicin was released at pH 5.0 (59.1 ± 2.1%) compared to physiological pH (34.9 ± 4.8%), confirming a pH-sensitive release profile. The in vitro cytotoxicity assay demonstrated that DOX-loaded nanoparticles can inhibit cancer cell proliferation and promote reduced cytotoxicity in non-tumor cells. The D45kP30k-DOX nanoparticles induced morphological changes in HCT-116 cells suggesting cell death and the cell uptake assay indicated that the nanoparticles can be internalized by endocytosis. Therefore, DOX-loaded nanoparticles exhibited potential as smart systems for cancer treatment. [Display omitted]