Synthesis of pH-sensitive nanocarriers based on polyacrylamide grafted nanocrystalline cellulose for targeted drug delivery to folate receptor in breast cancer cells

Abstract In this study, nanocrystalline cellulose (NCC) was prepared for the synthesis of new nanocarriers from microcrystalline cellulose to the targeted drug delivery of doxorubicin (DOX) and then a chlorinated derivative of the NCC was prepared as well. The chlorinated NCC was used as a macroinitiator in the atom transfer radical polymerization (ATRP) technique to graft polyacrylamide on NCC chains (PA-g-NCC). Then PA-g-NCC copolymer was further reacted to form the copolymer with amine pendant groups by the transamidation method. Finally, two pathways were followed for the synthesis of two nanocarriers. In the first pathway, carboxymethyl-β-cyclodextrin (CM-β-CD) was grafted to the aminated PA-g-NCC copolymer and then the synthesized nanocarrier was targeted by folic acid (FA) which was embedded into the cyclodextrin (CD) cavity via host-guest interaction. In the second pathway, the FA was directly grafted on the aminated PA-g-NCC copolymer without CD mediation. DOX as an anticancer drug was loaded into the nanocarriers spheres. The characterization of synthesized materials was performed by FT-IR, SEM, EDX, and TGA. Loading capacity was measured in-vitro drug release by using UV spectroscopy. To investigate the effect of drug-loaded nanocarriers on breast cancer cells, we cultured and treated MCF7 cells with drug-nanocarriers. The cell death rate was determined by the MTT assay and IC50 on culture medium.