Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab of Biomaterials, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, Key Laboratory for Nanomedicine, Guangdong Medical University, Dongguan, 523808, PR China.
Biomaterials. 2021 Feb;269:120639. doi: 10.1016/j.biomaterials.2020.120639. Epub 2021 Jan 4.
Sonodynamic therapy (SDT) is a promising approach for tumor treatment because of the noninvasion, and future would be perfect while it activates systemic immune responses through deep penetration to effectively avoid tumor recurrence. Here, a multifunctional nanosonosensitizer system (FA-MnPs) is designed by encapsulating manganese-protoporphyrin (MnP) into folate-liposomes. The nanoparticles of FA-MnPs not only exhibit excellent depth-responsive SDT but also simultaneously activate SDT-mediated immune response. Under US irradiation, FA-MnPs show the high acoustic intensity in mimic tissue up to 8 cm depth and generate amount of singlet oxygen (O). Density functional theory (DFT) calculations reveal that metal coordination in MnP has enhanced the US response ability. The good depth-responsed SDT of FA-MnPs efficiently suppresses the growth of not only the superficial tumors but also the deep lesion in the triple-negative breast cancer (TNBC) mice model. Importantly, FA-MnPs-induced SDT further re-polarizes immunosuppressive M2 macrophages to antitumor M1 macrophages, and elicits immunogenic cell death (ICD) to activate dendritic cells, T lymphocytes, and natural killercells (NK), which consequently trigger the antitumor immune, contributing to the tumor growth inhibition. This study put forward an idea for curing deep-seated and metastatic tumors through noninvasively depth-irradiated immunogenic SDT by reasonably designing multifunctional sonosensitizers.
声动力学疗法（SDT）是一种很有前途的肿瘤治疗方法，因为它是非侵入性的，而且未来通过深度渗透激活全身免疫反应将是完美的，从而有效地避免肿瘤复发。在这里，设计了一种多功能纳米声敏剂系统（FA-MnPs），通过将锰原卟啉（MnP）封装到叶酸脂质体中。FA-MnPs 纳米颗粒不仅表现出优异的深度响应 SDT，而且同时激活 SDT 介导的免疫反应。在超声照射下，FA-MnPs 在模拟组织中表现出高达 8cm 深度的高声强，并产生大量单线态氧（O）。密度泛函理论（DFT）计算表明，MnP 中的金属配位增强了 US 响应能力。FA-MnPs 的良好深度响应 SDT 不仅有效地抑制了三阴性乳腺癌（TNBC）小鼠模型中浅层肿瘤的生长，而且还抑制了深层病变的生长。重要的是，FA-MnPs 诱导的 SDT 进一步将免疫抑制性 M2 巨噬细胞重新极化为抗肿瘤 M1 巨噬细胞，并引发免疫原性细胞死亡（ICD）以激活树突状细胞、T 淋巴细胞和自然杀伤细胞（NK），从而引发抗肿瘤免疫，有助于抑制肿瘤生长。这项研究提出了一个通过合理设计多功能声敏剂，通过非侵入性深度辐照免疫原性 SDT 来治疗深部和转移性肿瘤的想法。
