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

简便合成近红外响应按需释放氧气纳米平台,用于精确的 MRI 引导治疗诊断缺氧诱导的三阴性乳腺癌肿瘤化学耐药性和转移

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作者:Dong Zhang #, Yuanyuan You #, Yuan Xu, Qingqing Cheng, Zeyu Xiao, Tianfeng Chen, Changzheng Shi, Liangping Luo

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.

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.

Methods

A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-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 O2-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 O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 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 O2-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.

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