Fabricating innovative nanomaterials for cancer treatment is essential for reducing its morbidity. The present study focuses on synthesizing, evaluating, and utilizing a bismuth nanosheet-reduced graphene oxide (BiNS-rGO) heterostructure for cancer combination therapy. The successful fabrication of the heterostructure with regulated thickness and morphology was confirmed by structural characterization using Fourier transform infrared spectroscopy, scanning transmission electron microscopy, and X-ray diffraction. Atomic force microscopy indicated the heterostructure height of 1.3 ± 0.95 nm. Moreover, high-resolution TEM confirmed the heterostructure configuration of the nanoparticles with a bismuth nanosheet (BiNS) plane distance of 0.33 nm. Following the evaluation of the photothermal characteristics of the BiNS-rGO heterostructure, it was found that a light-to-heat conversion of η = 67.6% was efficient under laser irradiation (3 W cm^-2, 5 min, 50 μg mL^-1, 1064 nm) to increase the temperature from 25 °C to 42.5 °C. The heterostructure demonstrated excellent photothermal stability and recyclability, making it highly promising for photothermal treatment (PTT) applications. At pH 7.4, 30% and 70.5% drug release were observed in 24 h and 240 h, respectively. Both pH and photothermal effect considerably impact the drug release profile. Drug release was increased in an acidic environment (pH 5.0) as opposed to physiological pH (pH 7.4), suggesting pH-sensitive behavior. In particular, over 24 hours, 42% of the medication was released at pH 5.0, while only 30% was released at pH 7.4 during the same time frame. Due to photothermal heating, the release rate increased even more after exposure to one-time NIR laser radiation (3 W cm^-2, 1064 nm). Under the same irradiation settings, drug release reached 52% in 24 hours, much higher than the 42% release at pH 7.4 under light. This implies that quicker drug diffusion was made possible by structural alterations in BiNS-rGO brought about by heat. A BiNS-rGO band gap and flat band potential of 1.86 eV and -0.68 V (vs. Ag/AgCl), respectively, confirm the radiocatalytic ROS generation. Following 96 h of incubation, the IC₅₀ value of BiNS-rGO was determined to be 121.30 μg mL^-1via MTT assay. Combination therapy showed much lower values, with BiNS-rGO + RT showing 53.41 μg mL^-1 and BiNS-rGO + MitoC + PTT + RT showing 19.43 μg mL^-1. Regarding the flow cytometry data, PTT, RT, and MitoC + PTT + RT treatment has shown an apoptosis ratio (early and late) of 36, 71.4, and 97.5%, respectively. Furthermore, the elevation of the caspase-3 apoptotic gene up to 23-fold in combination therapy confirmed the apoptotic cancer cell death pathway. Overall, this research demonstrates the potential of the BiNS-rGO heterostructure as a versatile nano-platform for combination cancer therapy that combines radiation, controlled drug delivery, and photothermal therapy with maximum efficacy and minimal side effects. This research study creates new opportunities for the development of sophisticated nanomaterials for targeted cancer therapy.

制备用于癌症治疗的创新纳米材料对于降低其发病率至关重要。本研究重点在于合成、评估和利用铋纳米片还原氧化石墨烯（BiNS-rGO）异质结构进行癌症联合疗法。通过傅里叶变换红外光谱、扫描透射电子显微镜和X射线衍射等结构表征方法确认了成功制备具有调节厚度和形态的异质结构。原子力显微镜显示该异质结构的高度为1.3±0.95纳米。此外，高分辨率TEM证实了纳米颗粒的异质结构配置，其铋纳米片（BiNS）晶格间距为0.33纳米。在评估BiNS-rGO异质结构的光热特性后发现，在激光照射下（3 W cm⁻², 5分钟，50 μg mL⁻¹, 1064 nm），光到热转换效率η=67.6%，能使温度从25°C升高至42.5°C。该异质结构表现出优异的光热稳定性和可回收性，对于光热治疗（PTT）应用具有高度潜力。在pH值为7.4时，在24小时和240小时内分别观察到30%和70.5%的药物释放量。pH值和光热效应显著影响了药物释放曲线。在酸性环境（pH 5.0）下，药物释放量高于生理pH值（pH 7.4），表明其具有pH敏感行为。特别是在24小时内，在pH 5.0时释放的药物超过42%，而在同一时间段内pH 7.4时仅释放了30%。由于光热加热，经一次近红外激光辐射后（3 W cm⁻², 1064 nm），药物释放量进一步增加。在相同的照射条件下，24小时内药物释放量达到了52%，远高于pH 7.4光照下的42%释放量。这表明BiNS-rGO的结构变化导致了热引起的快速药物扩散。BiNS-rGO的带隙和平带电位分别为1.86 eV 和 -0.68 V（相对于Ag/AgCl），证实其具有放射催化ROS生成的能力。通过MTT法，在96小时孵育后确定了BiNS-rGO的IC₅₀值为121.30 μg mL⁻¹。联合治疗表现出更低的有效浓度，其中BiNS-rGO + RT为53.41 μg mL⁻¹，而BiNS-rGO + MitoC + PTT + RT仅为19.43 μg mL⁻¹。根据流式细胞仪数据，在PTT、RT和MitoC+PTT+RT治疗下，早期和晚期凋亡比例分别为36%、71.4%和97.5%。此外，联合治疗中上调的caspase-3凋亡基因高达23倍，证实了细胞凋亡的癌症死亡途径。总体而言，该研究展示了BiNS-rGO异质结构作为具有多功能性的纳米平台用于联合癌症疗法的巨大潜力，集成了放射、控制释放药物和光热治疗，并最大限度地提高了疗效并减少了副作用。这项研究为开发用于靶向癌症治疗的复杂纳米材料提供了新的机会。