近红外响应型按需释氧纳米平台的简便合成用于精准 MRI 引导下治疗三阴性乳腺癌缺氧诱导的肿瘤化疗耐药和转移
Facile synthesis of near-infrared responsive on-demand oxygen releasing nanoplatform for precise MRI-guided theranostics of hypoxia-induced tumor chemoresistance and metastasis in triple negative breast cancer.
机构信息
Department of Medical Imaging Center, The First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
The Shunde Affiliated Hospital, Jinan University, Foshan, 528300, China.
出版信息
J Nanobiotechnology. 2022 Mar 4;20(1):104. doi: 10.1186/s12951-022-01294-z.
BACKGROUND
Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion.
METHODS
A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation.
RESULTS
The near-infrared responsive on-demand oxygen releasing nanoplatform O-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O-PPSiI could alleviate tumor hypoxia by releasing O within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O-PPSiI.
CONCLUSIONS
Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC.
背景
缺氧是导致三阴性乳腺癌（TNBC）化疗耐药和转移的重要因素，缓解缺氧微环境可以增强抗肿瘤疗效，抑制肿瘤侵袭。
方法
通过两阶段自组装过程成功合成了近红外（NIR）响应按需供氧纳米平台（O-PPSiI），以克服缺氧诱导的肿瘤化疗耐药性和转移。我们将载药的聚（乳酸-共-乙醇酸）核嵌入到超薄的二氧化硅壳中，该壳附着有顺磁 Gd-DTPA，以开发一种磁共振成像（MRI）引导的 NIR 响应按需药物释放纳米系统，其中吲哚菁绿被用作光热转换器，在 NIR 照射下触发氧气和药物释放。
结果
本研究通过两阶段自组装过程化学合成了近红外响应按需供氧纳米平台 O-PPSiI，它可以在 NIR 照射下输送和释放氧气，缓解缺氧，提高化疗疗效，并抑制肿瘤转移。这种智能设计具有以下优点：（i）该纳米系统中的 O 可以通过 NIR 响应的二氧化硅壳破裂精确释放；（ii）通过肿瘤的敏感 MRI 实时监测和定量分析，动态生物分布过程；（iii）O-PPSiI 可以通过 NIR 激光激发时在肿瘤内释放 O 来缓解肿瘤缺氧；（iv）协同治疗 NIR 触发的 O-PPSiI 可抑制 EMT 过程，从而减弱 TNBC 肿瘤的迁移和侵袭能力。
结论
我们的工作提出了一种基于 MRI 指导的智能策略，并为合理设计 NIR 响应按需药物释放纳米医学系统提供了一种有效的方法，用于 TNBC 的精确治疗。
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