Hyaluronic acid-conjugated graphene oxide/photosensitizer nanohybrids for cancer targeted photodynamic therapy

Hyaluronic acid (HA)-graphene oxide (GO) conjugates, with a high loading of photosensitizers (PS; Ce6), were developed as a cancer cell targeted and photoactivity switchable nanoplatform for photodynamic therapy (PDT). HA-GO conjugates with size below 100 nm were first prepared by the chemical conjugation between ADH-modified HA and fractionated GO sheets with size relevant for drug delivery. Before evaluating the drug delivery efficacies, their chemical structure, morphology, and biocompatibility were characterized by H-1 NMR, UV, TGA, AFM, DLS and MTT assays. The physical adsorption of Ce6 onto HA-GO nanocarriers was mainly due to the pi-pi stacking as well as hydrophobic interactions. It was demonstrated by CLSM and FACS that the cellular internalization of the HA-GO/Ce6 nanohybrids was much more effective when compared with free Ce6, which was also found to be significantly influenced by the co-treatment with an excess amount of HA polymers, illustrating their active targeting to HA receptors overexpressed on cancer cells. The photoactivity of Ce6 adsorbed on HA-GO nanocarriers was mostly quenched in aqueous solution to ensure biocompatibility, but was quickly recovered after the release of Ce6 from HA-GO nanocarriers upon cellular uptake. As a result, the PDT efficiency of the HA-GO/Ce6 nanohybrids was remarkably improved similar to 10 times more than that of free Ce6, as well demonstrated in both MTT and LIVE/DEAD assays.