Plasmonic gold nanostars for synergistic photoimmunotherapy to treat cancer

Abstract

Cancer is the second leading cause of death and there is an urgent need to improve cancer management. We have developed an innovative cancer therapy named Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by combining gold nanostars (GNS)-mediated photothermal ablation with checkpoint inhibitor immunotherapy. Our previous studies have demonstrated that SYMPHONY photoimmunotherapy not only treats the primary tumor but also dramatically amplifies anticancer immune responses in synergy with checkpoint blockade immunotherapy to treat remote and unresectable cancer metastasis. The SYMPHONY treatment also induces a 'cancer vaccine' effect leading to immunologic memory and prevents cancer recurrence in murine animal models. This manuscript provides an overview of our research activities on the SYMPHONY therapy with plasmonic GNS for cancer treatment.

Keywords: cancer; gold nanostars; photoimmunotherapy.

Figure 1:

(A) Transmission electron microscopy (TEM) image of the synthesized GNS nanoprobe. (B) Electromagnetic field simulation shows significantly enhanced electromagnetic field at GNS tips. (Adapted from Ref [18, 38]).

Figure 2:

(A) Heating comparison of a phantom with and without GNS under 808 and 1064 nm laser irradiation. The laser power density was set to be 0.6 W/cm² and a thermocouple probe was used to measure the temperature at 1-s intervals. (B) Heating comparison of GNS with gold nanoshells under 808 nm laser irradiation. (Adapted from Ref [19]).

Figure 3:

(A) Maximum intensity projection of dual-energy CT images for the tumor in the hind leg 0.5 and 72 h after intravenous injection of GNS. The green color shows GNS concentration in the range of 2–10 mg/ml and the gray color shows tissues windowed from −100 to 5000 HU. (B) Dual-energy CT image for tumor 72 h after GNS intravenous injection. The green color shows GNS in the concentration range from 2.5 to 8 mg/ml and the gray color shows tissues windowed from −500 to 1200 HU. (Adapted from Ref [19]).

Figure 4:

(A) In vivo SERS spectrum measured in the tumor and healthy muscle 72 h after intravenous injection of GNS SERS nanoprobe. Unique SERS peaks can be detected in the tumor but not healthy muscle. The tumor shows black color due to a high uptake of GNS which absorbs light strongly. (B) SERS spectrum of GNS nanoprobe in the solution at pH 5 (black) and pH 9 (red). (Adapted from Ref [19, 39]).

Figure 5:

(A) Thermal imaging with a near-infrared camera to monitor tumor temperature change under laser irradiation with and without GNS. The temperate scale bar is from 23 to 60 °C. T shows tumor location and H represents the mouse head. (B) Tumor temperature change profile for the mouse with IV injection of GNS or phosphate-buffered saline (control). (C) Photographs of mice before and after laser treatment with and without GNS injection. The tumor size for the mouse with both GNS injection and laser irradiation had a clear tumor size decrease while the tumor for the mouse with only laser irradiation grew quickly. (Adapted from Ref [19]).

Figure 6:

Primary tumor size changes profile for the mice with SYMPHONY treatment (A) and blank control (B). Distant tumor size changes profile for the mice with SYMPHONY treatment (C) and blank control (D). The laser irradiation of photothermal therapy was performed only on the primary tumor. The line stopped (× sign in black color) if the mouse was sacrificed due to a large tumor or ulceration. (Adapted from Ref [37]).

Figure 7:

(A) Kaplan–Meier (K-M) overall survival curve. At the end of 49 days, only the SYMPHONY (GNS + Laser + Anti PDL1) group had two surviving mice (40%) and only this group had one mouse that survived after 100 days; all other control groups have no survival mice. (B) For the tumor-free mouse from SYMPHONY therapy, no tumor developed after rechallenge indicating the existence of memorized anticancer immune responses. (Adapted from Ref [37]).