期刊
PHARMACEUTICS
卷 14, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14020253
关键词
hypoxia; micelles; bioreductive prodrug; phototherapy; antitumor
资金
- National Natural Science Foundation of China [51603101]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX21_0545]
This study developed a near-infrared light-decomposable nanomicelle for controlled delivery of a hypoxia-activated bioreductive prodrug, which showed remarkable tumor cell-killing potential in breast cancer cells and significant tumor accumulation and inhibition of lung metastasis in mice, making it a promising strategy for hypoxia-enhanced phototherapies against metastatic breast cancer.
Oxygen dependence and anabatic hypoxia are the major factors responsible for the poor outcome of photodynamic therapy (PDT) against cancer. Combining of PDT and hypoxia-activatable bioreductive therapy has achieved remarkably improved antitumor efficacy compared to single PDT modality. However, controllable release and activation of prodrug and safety profiles of nanocarrier are still challenging in the combined PDT/hypoxia-triggered bioreductive therapy. Herein, we developed a near infrared (NIR) light-decomposable nanomicelle, consisting of PEGylated cypate (pCy) and mPEG-polylactic acid (mPEG(2k)-PLA(2k)) for controllable delivery of hypoxia-activated bioreductive prodrug (tirapazamine, TPZ) (designated TPZ@pCy), for combating metastatic breast cancer via hypoxia-enhanced phototherapies. TPZ@pCy was prepared by facile nanoprecipitation method, with good colloidal stability, excellent photodynamic and photothermal potency, favorable light-decomposability and subsequent release and activation of TPZ under irradiation. In vitro experiments demonstrated that TPZ@pCy could be quickly internalized by breast cancer cells, leading to remarkable synergistic tumor cell-killing potential. Additionally, metastatic breast tumor-xenografted mice with systematic administration of TPZ@pCy showed notable tumor accumulation, promoting tumor ablation and lung metastasis inhibition with negligible toxicity upon NIR light illumination. Collectively, our study demonstrates that this versatile light-decomposable polymeric micelle with simultaneous delivery of photosensitizer and bioreductive agent could inhibit tumor growth as well as lung metastasis, representing a promising strategy for potent hypoxia-enhanced phototherapies for combating metastatic breast cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据