Department of Applied Physics, University of Eastern Finland, Kuopio 70211, Finland.
Department of Pharmaceutical Chemistry and Analysis, Airforce Medical University, 169th Changle West Road, Xi'an, Shaanxi 710032, China; Department of Oncology, The Air Force Hospital from Eastern Theater of PLA, Nanjing 210001, China.
Acta Biomater. 2022 Oct 15;152:473-483. doi: 10.1016/j.actbio.2022.08.073. Epub 2022 Sep 8.
Photothermal therapy (PTT) in combination with other treatment modalities has shown great potential to activate immunotherapy against tumor metastasis. However, the nanoparticles (NPs) that generate PTT have served as the photothermal agent only. Moreover, researchers have widely utilized highly immunogenic tumor models to evaluate the immune response of these NPs thus giving over-optimistic results. In the present study black porous silicon (BPSi) NPs were developed to serve as both the photothermal agent and the adjuvant for PTT-based antitumor immunotherapy. We found that the poorly immunogenic tumor models such as B16 are more valid to evaluate NP-based immunotherapy than the widely used immunogenic models such as CT26. Based on the B16 cancer model, a cocktail regimen was developed that combined BPSi-based PTT with doxorubicin (DOX) and cytosine-phosphate-guanosine (CpG). BPSi-based PTT was an important trigger to activate the specific immunotherapy to inhibit tumor growth by featuring the selective upregulation of TNF-α. Either by adding a low dose DOX or by prolonging the laser heating time, a similar efficacy of immunotherapy was evoked to inhibit tumor growth. Moreover, BPSi acted as a co-adjuvant for CpG to significantly boost the immunotherapy. The present study demonstrates that the BPSi-based regimen is a potent and safe antitumor immunotherapy modality. Moreover, our study highlighted that tuning the laser heating parameters of PTT is an alternative to the toxic cytostatic to evoke immunotherapy, paving the way to optimize the PTT-based combination therapy for enhanced efficacy and decreased side effects. STATEMENT OF SIGNIFICANCE: Tumor metastasis causes directly or indirectly more than 90% of cancer deaths. Combination of photothermal therapy (PTT), chemotherapy and immunotherapy based on nanoparticles (NPs) has shown great potential to inhibit distant and metastatic tumors. However, these NPs typically act only as photothermal agents and many of them have been evaluated with immunogenic tumor models. The present study developed black porous silicon working as both the photothermal conversion agent and the immunoadjuvant to inhibit distant tumor. It was recognized that the poorly immunogenic tumor model B16 is more appropriate to evaluate immunotherapy than the widely used immunogenic model CT26. The coordination mechanism of the PTT-based combination therapy regimen was discovered in detail, paving the way to optimize cancer immunotherapy for enhanced efficacy and decreased side effects.
光热疗法（PTT）与其他治疗方式相结合，已显示出在激活抗肿瘤转移免疫疗法方面的巨大潜力。然而，用于产生 PTT 的纳米颗粒（NPs）仅作为光热剂发挥作用。此外，研究人员广泛利用高免疫原性肿瘤模型来评估这些 NPs 的免疫反应，从而得出过于乐观的结果。在本研究中，开发了黑色多孔硅（BPSi） NPs 作为光热剂和基于 PTT 的抗肿瘤免疫治疗的佐剂。我们发现，像 B16 这样的低免疫原性肿瘤模型比广泛使用的免疫原性模型（如 CT26）更适合评估基于 NPs 的免疫疗法。基于 B16 癌症模型，开发了一种鸡尾酒方案，将基于 BPSi 的 PTT 与多柔比星（DOX）和胞嘧啶-磷酸-鸟嘌呤（CpG）联合使用。基于 BPSi 的 PTT 通过选择性地上调 TNF-α 成为激活特异性免疫治疗以抑制肿瘤生长的重要触发因素。通过添加低剂量 DOX 或延长激光加热时间，都能诱发类似的免疫治疗效果来抑制肿瘤生长。此外，BPSi 作为 CpG 的佐剂，显著增强了免疫治疗效果。本研究表明，基于 BPSi 的方案是一种有效且安全的抗肿瘤免疫治疗方式。此外，我们的研究强调，调整 PTT 的激光加热参数是一种替代有毒细胞抑制剂的方法，可以引发免疫治疗，为优化基于 PTT 的联合治疗以提高疗效和降低副作用铺平道路。
肿瘤转移直接或间接导致 90%以上的癌症死亡。基于纳米颗粒（NPs）的光热疗法（PTT）、化疗和免疫疗法的组合已显示出抑制远处和转移性肿瘤的巨大潜力。然而，这些 NPs 通常仅作为光热剂发挥作用，并且许多 NPs 已在免疫原性肿瘤模型中进行了评估。本研究开发了黑色多孔硅，将其用作光热转换剂和免疫佐剂来抑制远处肿瘤。研究发现，低免疫原性肿瘤模型 B16 比广泛使用的免疫原性模型 CT26 更适合评估免疫疗法。详细揭示了基于 PTT 的联合治疗方案的协调机制，为优化癌症免疫治疗以提高疗效和降低副作用铺平了道路。
