pH responsive doxorubucin loaded zein nanoparticle crosslinked pectin hydrogel as effective site-specific anticancer substrates.

Herein, we report pH-responsive hydrogels of hierarchically self-assembled protein (zein, in the form of its nanoparticles of size 80-120 nm) and polysaccharide (pectin), where gelation occurred below pH 3 in the absence of crosslinkers, which we used for encapsulation and release of anticancer drug, Doxorubicin (DOX) in the cell nucleus. These nanoparticles, spherical in shape, in addition to helping in the formation of gel network also encapsulate the drug and pectin layer adsorbed on the surface of these nanoparticle allows for the drying, redispersion and enhanced swelling. A monovalent salt-dependent study performed in the concentration range of 1-100 mM clearly showed the associative interaction between the zein nanoparticles and pectin chains were hydrophobic in nature. FTIR results confirmed the loading of the drug inside the nanoparticles. Melting profile studies of these gels revealed that encapsulation of drug did not change the thermo-physical properties. Doxorubicin drug loaded hydrogels exhibited superior cytotoxicity towards cervical cancer cell lines by inducing intracellular-antioxidative stress-based apoptosis. Confocal microscopy revealed that the hydrogels required quite less time of 4 h to completely penetrate the cells assisted by the charge specific electrostatic interaction between the negatively charged HeLa cells and positively charged crosslinks. The data, further revealed that these pH specific hydrogels were suitable for release of the drug in cell nucleus is assisted by the acidic environment of cellular organelles, and hence have a potential in cancer therapy with minimal collateral damage to healthy cells.