Injectable and self-healing nanocomposite hydrogel loading needle-like nano-hydroxyapatite and graphene oxide for synergistic tumour proliferation inhibition and photothermal therapy.

Abstract

Non-chemotherapeutic tumour treatment has received extensive attention due to its having fewer side effects as compared to chemotherapy. However, nanomaterials-based non-chemotherapy still faces limitations such as poor targeting and low retention. Therefore, a Schiff base cross-linked hydrogel was designed and prepared using aldehyde-modified polyethylene glycol (PEG) and carboxymethyl chitosan (CMC). This hydrogel has good injectable and self-healing properties and can carry graphene oxide (GO) as a photothermal agent and needle-like nano-hydroxyapatite (HAP) as a tumour inhibitor. Combined with tumour proliferation inhibition therapy and photothermal therapy, the nanocomposite hydrogel system can avoid the side effects of chemotherapy and improve the accuracy of tumour treatment. The PEG-CMC/HAP/GO nanocomposite hydrogel system has a porous structure, good injectability and self-healing properties to meet the mechanical requirements. In vitro cell characterization showed that GO is phototoxic to tumour cells, HAP can inhibit the proliferation of tumour cells, the nanocomposite hydrogel remained in the tumour site, and the encapsulated GO and HAP did not transfer to the normal site and cause cell damage. In the in vivo investigation, the breast cancer tumour-bearing mice, the model animals for tumour treatment, were treated with an intratumoral injection of the PEG-CMC/HAP/GO nanocomposite hydrogel. This functional self-healing hydrogel loaded with GO and HAP effectively inhibited tumour cell proliferation and realized the synergistic effect of photothermal therapy, which is expected to become a new effective treatment approach for tumours.