Understanding and implementing the ordered supramolecular assembly in organic photothermal materials is challenging, yet significant, for photothermal performance enhancement. Herein, an amphipathic squaraine dye (PSQ) with a poly (ethylene glycol) chain attached as a hydrophilic anchor is synthesized. In aqueous solution, PSQ spontaneously self‐assembles into uniform nanospheres (PSQ‐NSs) with well‐defined H‐dimeric substructures. Molecular dynamics simulations are conducted to illustrate the self‐assembly process. Reorganization energy calculations show that nonradiative decay is accelerated by H‐dimeric PSQ low‐frequency out‐of‐plane vibrational modes, which enables a rapid dissipation of excited‐state energy to heat. As such, the resultant H‐dimeric PSQ‐NSs exhibit ultrahigh photothermal conversion efficiency (81.2%) under laser irradiation (0.3 W cm−2, 808 nm) in water. In vitro and in vivo evaluations confirm their high stability, biocompatibility, tumor accumulation, and efficient tumor inhibition in photothermal therapy. It is expected that the self‐assembling H‐dimers will become a unique platform for the precise designing of small‐molecule PTAs for future clinical PTT applications.

While dendritic cell (DC)-based immunotherapy has achieved satisfactory results in animal models, its effects were not satisfactory as initially expected in clinical applications, despite the safety and varying degrees of effectiveness in various types of cancer. Improving the efficacy of the DC-based vaccine is essential for cancer immunotherapy. The present study aimed to investigate methods with which to amplify and enhance the antitumor immune response of a DC-based tumor vaccine by silencing the expression of indoleamine 2,3-dioxygenase 2 (IDO2), a tryptophan rate-limiting metabolic enzyme in DCs. In vitro experiments revealed that the silencing of IDO2 in DCs did not affect the differentiation of DCs, whereas it increased their expression of costimulatory molecules following stimulation with tumor necrosis factor (TNF)-α and tumor lysate from Lewis lung cancer (LLC) cells. In a mixed co-culture system, the IDO2-silenced DCs promoted the proliferation of T-cells and reduced the induction of regulatory T-cells (Tregs). Further in vivo experiments revealed that the silencing of IDO2 in DCs markedly suppressed the growth of tumor cells. Moreover, treatment with the IDO2-silenced DC-based cancer vaccine enhanced cytotoxic T lymphocyte activity, whereas it decreased T-cell apoptosis and the percentage of CD4 + CD25 + Foxp3 + Tregs. On the whole, the present study provides evidence that the silencing of the tryptophan rate-limiting metabolic enzyme, IDO2, has the potential to enhance the efficacy of DC-based cancer immunotherapy.

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Tumor-specific targeted delivery is a major obstacle to clinical treatment of hepatocellular carcinoma (HCC). Here we have developed a novel multi-functional nanostructure GAL-GNR-siGPC-3, which consists of Galactose (GAL) as the HCC-targeting moiety, golden nanorods (GNR) as a framework to destroy tumor cells under laser irradiation, and siRNA of Glypican-3 (siGPC-3) which induce specifically gene silence of GPC-3 in HCC. Glypican-3 (GPC-3) gene is highly associated with HCC and is a new potential target for HCC therapy. On the other hand, Gal can specifically bind to the asialoglycoprotein receptor which is highly expressed on membrane of hepatoma cells. GAL and siGPC-3 can induce targeted silencing of GPC-3 gene in hepatoma cells. In vivo and in vitro results showed that GAL-GNR-siGPC-3 could significantly induce downregulation of GPC-3 gene and inhibit the progression of HCC. More notably, GAL-GNR-siGPC-3 could induce both GPC-3 gene silencing and photothermal effects, and the synergistic treatment of tumors was more effective than individual treatments. In summary, GAL-GNR-siGPC-3 achieved a synergistic outcome to the treatment of cancer, which opens up a new approach for the development of clinical therapies for HCC.