Daunting challenges in investigating the controlled release of drugs in complicated intracellular microenvironments demand the development of stimuli-responsive drug delivery systems. Here, a nanoparticle system, CaF2:Tm,Yb@mSiO2, made of a mesoporous silica (mSiO2) nanosphere with CaF2:Tm,Yb upconversion nanoparticles (UCNPs) is developed, filling its mesopores and with its surface-modified with polyacrylic acid for binding the anticancer drug molecules (doxorubicin, DOX). The unique design of CaF2:Tm,Yb@mSiO2 enables us to trigger the drug release by two mechanisms. One is the pH-triggered mechanism, where drug molecules are preferentially released from the nanoparticles at acidic conditions unique for the intracellular environment of cancer cells compared to normal cells. Another is the 808 nm near infrared (NIR)-triggered mechanism, where 808 nm NIR induces the heating of the nanoparticles to weaken the electrostatic interaction between drug molecules and nanoparticles. In addition, luminescence resonance energy transfer occurs from the UCNPs (the energy donor) to the DOX drug (the energy acceptor) in the presence of 980 nm NIR irradiation, allowing us to monitor the drug release by detecting the vanishing blue emission from the UCNPs. This study demonstrates a new multifunctional nanosystem for dual-triggered and optically monitored drug delivery, which will facilitate the rational design of personalized cancer therapy.

中文翻译：

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用于双触发和光学监测多柔比星递送的多功能纳米晶 CaF2:Tm,Yb@mSiO2 系统

在复杂的细胞内微环境中研究药物控制释放的艰巨挑战需要开发刺激响应性药物递送系统。在这里，开发了一种纳米粒子系统 CaF2:Tm,Yb@mSiO2，由介孔二氧化硅 (mSiO2) 纳米球和 CaF2:Tm,Yb 上转换纳米粒子 (UCNPs) 制成，填充其介孔并用聚丙烯酸进行表面改性结合抗癌药物分子（阿霉素，DOX）。CaF2:Tm,Yb@mSiO2 的独特设计使我们能够通过两种机制触发药物释放。一种是 pH 触发机制，与正常细胞相比，在癌细胞的细胞内环境所特有的酸性条件下，药物分子优先从纳米颗粒中释放出来。另一个是 808 nm 近红外 (NIR) 触发机制，其中 808 nm NIR 会引起纳米颗粒的加热，从而削弱药物分子和纳米颗粒之间的静电相互作用。此外，在 980 nm NIR 照射下，发光共振能量从 UCNPs（能量供体）转移到 DOX 药物（能量受体），使我们能够通过检测 UCNPs 消失的蓝色发射来监测药物释放. 这项研究展示了一种用于双触发和光学监测药物递送的新型多功能纳米系统，这将有助于个性化癌症治疗的合理设计。在 980 nm NIR 照射下，发光共振能量从 UCNPs（能量供体）转移到 DOX 药物（能量受体），使我们能够通过检测 UCNPs 消失的蓝色发射来监测药物释放。这项研究展示了一种用于双触发和光学监测药物递送的新型多功能纳米系统，这将有助于个性化癌症治疗的合理设计。在 980 nm NIR 照射下，发光共振能量从 UCNPs（能量供体）转移到 DOX 药物（能量受体），使我们能够通过检测 UCNPs 消失的蓝色发射来监测药物释放。这项研究展示了一种用于双触发和光学监测药物递送的新型多功能纳米系统，这将有助于个性化癌症治疗的合理设计。