Multifunctionized Gold Nanostars for Combinatorial NIR-II Photothermal and Immuno Cancer Therapy
Among different types of gold nanoparticles, anisotropic gold nanostars (AuNS) are superior to others due to their biocompatibility, ease of synthesis, tunable localized surface plasmon resonance in the near-infrared (NIR) region and higher drug-loading capacity compared to the spherical AuNPs with the same sizes. Here we will first present the construction of multifunctional AuNS for efficient delivery of therapeutic oligonucleotides, which are attracting drug candidates in modulating disease-associated molecular signaling, to target cells. Subsequently, we will focus on the multifunctional NIR-II AuNS decorated with CpG, an oligodeoxynucleotide that could activate the innate immune system via binding to the toll-like receptor 9. Multifunctional AuNS could accumulate to the tumor tissue through passive infiltration. In situ treatment of tumors with NIR-II light brought up a sequential events: on the one hand, photothermal ablation induced immunogenic cell death, increased the expression of damage-associated molecular patterns and boosted the anticancer immune responses; on the other hand, CpG activated antigen presentation cells and enhanced the activation of effector T cells to eliminate tumor cells. Finally, the multifunctional AuNS in combination with NIR-II light showed greater inhibition of tumor growth and complete tumor eradication was achieved via the reversal of the immunosuppressive tumor microenvironment by anti-PD-1 antibody.