Department of Lymphoma, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, 24 Huanhu West Road, Hexi District, Tianjin, 300060, People's Republic of China.
Department of Lymphatic Comprehensive Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450001, Henan, China.
J Nanobiotechnology. 2021 Jun 13;19(1):181. doi: 10.1186/s12951-021-00932-2.
BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive malignant disease with a high rate of recurrence and metastasis, few effective treatment options and poor prognosis. Here, we designed and constructed a combined photothermal immunotherapy strategy based on cancer cell membrane-coated biomimetic black phosphorus quantum dots (BBPQDs) for tumor-targeted photothermal therapy and anti-PD-L1 mediated immunotherapy. RESULTS: BBPQDs have good photothermal conversion efficiency and can efficiently target tumor cells through homologous targeting and tumor homing. Under near infrared irradiation, we found that BBPQDs kill tumors directly through photothermal effects and induce dendritic cells maturation. In vivo studies have confirmed that the combined photothermal immunotherapy strategy displays a stronger antitumor activity than anti-PD-L1 monotherapy. In addition, BBPQDs-mediated photothermal therapy in combination with anti-PD-L1 treatment inhibit tumor recurrence and metastasis by reprograming the immunosuppressive tumor microenvironment into an immune-active microenvironment, and promoting the local and systemic antitumor immune response. We further found that the combined photothermal immunotherapy strategy can produce an immune memory effect against tumor rechallenge. CONCLUSIONS: This study provides a novel therapeutic strategy for inhibiting the recurrence and metastasis of TNBC, with broad application prospects.
背景:三阴性乳腺癌(TNBC)是一种侵袭性强、复发转移率高、治疗选择少、预后差的恶性肿瘤。本研究设计并构建了一种基于细胞膜包覆仿生黑磷量子点(BBPQDs)的联合光热免疫治疗策略,用于肿瘤靶向光热治疗和抗 PD-L1 介导的免疫治疗。
结果:BBPQDs 具有良好的光热转换效率,通过同源靶向和肿瘤归巢可高效靶向肿瘤细胞。近红外光照射下,我们发现 BBPQDs 通过光热效应直接杀伤肿瘤,并诱导树突状细胞成熟。体内研究证实,联合光热免疫治疗策略比抗 PD-L1 单药治疗具有更强的抗肿瘤活性。此外,BBPQDs 介导的光热治疗联合抗 PD-L1 治疗通过将免疫抑制性肿瘤微环境重编程为免疫活性微环境,抑制肿瘤的复发和转移,并促进局部和全身抗肿瘤免疫反应。我们进一步发现,联合光热免疫治疗策略可以对肿瘤再挑战产生免疫记忆效应。
结论:本研究为抑制 TNBC 的复发和转移提供了一种新的治疗策略,具有广阔的应用前景。
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