pH and glutathione dual-triggered supramolecular assemblies as synergistic and controlled drug release carriers

A pH and glutathione (GSH) dual bio-relevant triggered supramolecular system is constructed through the non-covalent host-guest interactions between the adamantane (ADA) on camptothecin (CPT) and beta-cyclodextrin (beta-CD) on the side chain of the backbone of hyaluronic acid (HA). The obtained non-covalent supramolecular beta-CD-g-OX-HA/ADA-CPT complex could further self-assemble into a stable uniform sphere micellar structure with constant drug loading content in the extracellular environment but is cleaved in the cytosol of the cancer cells due to the acidic environment and the presence of a high concentration of GSH, resulting in a synergistic-fast pH and GSH triggered drug releasing behavior. The cytotoxicity of the supramolecular beta-CD-g-OX-HA/ADA-CPT micelles was investigated using Hep G2 cancer cells by MTT assays, which displayed that supramolecular beta-CD-g-OX-HA/ADA-CPT micelles had exhibited enhanced cellular proliferation inhibition against Hep G2 cancer cells compared to the free CPT, while the beta-CD-g-OX-HA had good cell compatibility. In vivo studies of the beta-CD-g-OX-HA/ADA-CPT micelles showed a higher in vivo efficacy without side effects and also confirmed the compatibility of the beta-CD-g-OX-HA. It is anticipated that this supramolecular complex will give the possibility to fabricate new types of bio-relevant triggered nanocarriers for cancer therapy.