Abstract
The complex and heterogeneous nature of cancer necessitates the development of innovative multifunctional nanomedicines (MN). Hyaluronic acid (HA) is a functional carbohydrate polysaccharide that is widely used in various biomedical fields. In this study, we employed HA as a stabilizer and regulator for the synthesis of a size-tunable nanomedicine comprising ferric ions, doxorubicin, and epigallocatechin gallate (EGCG), referred to as HDE-MN, for cancer therapy. A change in the HA ratio can yield HDE-MNs with sizes varying from ~20nm to over 100nm. Modified HA can respond to hyaluronidase (HAase) to provide controllable pH/HAase dual-responsive drug release for improved cancer therapy. Moreover, HA can mediate the targeted delivery of HDE-MNs both in vitro and in vivo to cancer cells. In addition, HDE-MNs reversed multidrug resistance owing to the incorporation of EGCG, inducing ferroptosis due to the involvement of ferric ions. More importantly, HDE-MNs have a photothermal conversion effect, enabling photothermal therapy, photothermally enhanced drug release, and ferroptosis, which collectively contribute to significantly improved cancer therapy. Therefore, the HDE-MNs with laser irradiation achieved full ablation of the in vivo tumors. Together with its good biocompatibility, HDE-MNs may be promising for effective cancer therapy.
Published Version
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