Interleukin-15 (IL-15) stimulates the proliferation of CD8+ T lymphocytes and activates cytotoxic T lymphocytes, memory CD8+ T cells, and natural killer cells, demonstrating broad application prospects in cancer immunotherapy. The activation of effector cells by IL-15 relies on a unique trans-presentation signaling mechanism. This process involves the initial binding of IL-15 to IL-15 receptor alpha (IL-15Rα) to form the IL-15/IL-15Rα complex, followed by binding of this complex to the IL-15 receptor beta/gamma (IL-15Rβ/γ) on target cells, thus exerting its pharmacological effects. The clinical application of recombinant interleukin-15 (rIL-15) faces challenges including its short half-life time and limited availability of endogenous IL-15 receptor alpha (IL-15Rα). Additionally, the immunosuppressive tumor microenvironment impairs its anti-tumor efficacy. In this study, a recombinant IL-15Rα-sushi-HSA fusion protein (rILR-HSA) is designed and expressed, which comprises the IL-15Rα sushi domain fused to human serum albumin (HSA). The co-hitchhiking drug delivery system, rILR-HSA/BPBBT/rIL-15 nanoparticles, prepared by the hydrophobic binding between the HSA component and the photothermal agent molecule BPBBT, followed by the high-affinity binding between IL-15Rα-sushi and rIL-15. Compared with free rIL-15, rILR-HSA/BPBBT/rIL-15 nanoparticles extend the serum half-life time of rIL-15 by 2.6-fold. Simultaneously, the tumor accumulation of rILR-HSA/BPBBT/rIL-15 nanoparticles in the orthotopic CT26-Luc colon cancer-bearing mice facilitates intraoperative near-infrared window-Ⅱ fluorescence image-guided photothermal immunotherapy. The co-hitchhiking drug delivery strategy employs a fusion protein carrier to co-deliver rIL-15 and photothermal agent, providing an approach for safe and effective IL-15-based photothermal immunotherapy of tumor. Animal experiments were conducted with the approval of the Institutional Animal Care and Use Committee of the School of Pharmacy, Fudan University (ethics number: 2018-09-YJ-LW-01).
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |