光动力疗法（PDT）已成为一种有效的非侵入性癌症治疗方法。然而，有机小分子光敏剂往往存在疏水性缺陷、光稳定性差以及聚集导致的猝灭等缺陷，限制了其应用。通常，载体辅助药物递送系统是解决上述障碍的常用策略，但额外的载体材料可能会增加潜在生物毒性的风险。随后提出了易于制备和高载药量的无载体药物递送系统作为开发疏水性药物临床应用的潜在策略。在此，我们合理设计了三种基于IR780的无载体纳米系统，由碳/二硫键/二硒化物键共轭的基于IR780的同二聚体形成。基于IR780的同型二聚体可以自组装形成纳米颗粒（DC-NP、DS-NP、DSe-NP），并表现出比游离IR780更高的活性氧生成能力和光稳定性，其中DSe-NP在808 nm激光照射下表现出更高的活性氧生成能力和光稳定性。最好并对 4T1 细胞产生最强的细胞毒性。同时，DSe-NP的谷胱甘肽消耗能力增强了其PDT效应，然后诱导4T1细胞过度氧化应激，通过进一步增强免疫原性细胞死亡来增强抗肿瘤功效。在荷瘤小鼠中，DSe-NP表现出明显的肿瘤部位聚集，明显抑制肿瘤生长和转移，并通过有效诱导树突状细胞成熟、激活T淋巴细胞和自然杀伤细胞来增强免疫效果。总之，我们的研究提出了一种基于IR780的无载体纳米递送系统，用于PDT和免疫治疗的结合，并通过无载体药物递送系统的方法扩大了有机小分子光敏剂的应用。

Photodynamic therapy (PDT) has emerged as an efficient approach for non-invasive cancer treatment. However, organic small-molecule photosensitizers are often associated with defects in hydrophobicity, poor photostability, and aggregation-caused quenching, which limit their application. Usually, the carrier-assisted drug delivery system is a common strategy to solve the above obstacles, but additional carrier material could increase the risk of potential biological toxicity. The carrier-free drug delivery system with easy preparation and high drug-loading capability is proposed subsequently as a potential strategy to develop the clinical use of hydrophobic drugs. Herein, we rationally designed three IR780-based carrier-free nanosystems formed by carbon/disulfide/diselenide bond conjugated IR780-based homodimers. The IR780-based homodimers could self-assemble to form nanoparticles (DC-NP, DS-NP, DSe-NP) and exhibited higher reactive oxygen species generation capability and photostability than free IR780, in which DSe-NP with 808 nm laser irradiation performed best and resulted in the strongest cytotoxicity to 4T1 cells. Meanwhile, the glutathione consumption ability of DSe-NP boosted its PDT effect and then induced excessive oxidative stress of 4T1 cells, increasing antitumor efficacy by enhancing immunogenic cell death further. In tumor-bearing mice, DSe-NP displayed obvious tumor site accumulation, which obviously inhibited tumor growth and metastasis, and enhanced the immunological effect by effectively inducing dendritic cells to mature and activating T lymphocytes and natural killer cells. In summary, our study presented an IR780-based carrier-free nanodelivery system for a combination of PDT and immunity therapy and established expanding the application of organic small-molecule photosensitizers by an approach of carrier-free drug delivery system.