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

Abstract

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 1H NMR, UV, TGA, AFM, DLS and MTT assays. The physical adsorption of Ce6 onto HA–GO nanocarriers was mainly due to the π–π 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 ∼10 times more than that of free Ce6, as well demonstrated in both MTT and LIVE/DEAD assays.