Dual‐targeting multifunctional hyaluronic acid ligand‐capped gold nanorods with enhanced endo‐lysosomal escape ability for synergetic photodynamic–photothermal therapy of cancer

Abstract Au nanorods (AuNRs) have attracted considerable interest as drug delivery systems because of their enhanced cell internalization and stronger drug‐loading ability. In addition, the incorporation of photodynamic therapy (PDT) and photothermal therapy (PTT) into one nanosystem presents great promise to defect multiple drawbacks in cancer therapy. Herein, we fabricated a multifunctional and dual‐targeting nanoplatform based on hyaluronic acid‐grafted‐(mPEG/triethylenetetramine‐conjugated‐lipoic acid/tetra(4‐carboxyphenyl)porphyrin/folic acid) polymer ligand capped AuNRs (AuNRs@HA‐g‐(mPEG/Teta‐co‐(LA/TCPP/FA)) for combined photodynamic–photothermal therapy of cancer. The prepared nanoparticles displayed high TCPP loading capacity and excellent stability in different biological media. Furthermore, AuNRs@HA‐g‐(mPEG/Teta‐co‐(LA/TCPP/FA)) not only could produce a localized hyperthermia to conduct PTT, but also generate cytotoxic singlet oxygen ( 1 O 2 ) to perform PDT under laser irradiation. Confocal imaging results disclosed that this nanoparticle endowing the specific function of polymeric ligand could enhance cellular uptake, accelerate endo/lysosomal escape, as well as produce higher reactive oxygen species. Importantly, this combination therapy strategy could also induce higher anticancer potential than PDT or PTT only against MCF‐7 tumor cells in vitro. Therefore, this work presented an AuNRs‐based therapeutic nanoplatform with great potential in dual‐targeting and photo‐induced combination therapy of cancer.