用于体内肿瘤低温光热疗法敏化的一体化工程多功能纳米平台,ACS Nano

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用于体内肿瘤低温光热疗法敏化的一体化工程多功能纳米平台
ACS Nano ( IF 15.8 ) Pub Date : 2023-10-15 , DOI: 10.1021/acsnano.3c05991
Ke Li _{1,

2} , Kun Xu ₁ , Shaopeng Liu ₁ , Ye He ₂ , Meijun Tan ₁ , Yulan Mao ₁ , Yulu Yang ₁ , Jing Wu ₁ , Qian Feng ₁ , Zhong Luo ₃ , Kaiyong Cai ₁

Affiliation

低温光热疗法（PTT）是一种无创方法，利用低温下的光热效应选择性地消灭肿瘤细胞，同时保护正常组织，最大限度地减少热损伤，提高治疗安全性。首先，我们在低温处理后在基因水平上评估了肿瘤细胞的转录组，并观察到参与细胞周期和热响应相关信号通路的基因显着富集。为了应对这一挑战，我们开发了一种工程多功能纳米平台，为低温 PTT 的高效敏化提供了一体化策略。具体来说，我们利用MoS ₂纳米粒子作为光热核心来产生低温（40-48°C）。该纳米平台涂有DPA以负载CPT-11和Fe ²⁺，并用PEG和iRGD进一步修饰以增强肿瘤特异性（MoS ₂ /Fe@CPT-11-PEG-iRGD）。激光和酸触发释放CPT-11可显着增加细胞内H ₂ O ₂含量，并与Fe ²⁺离子配合增加细胞内脂质ROS含量，激活铁死亡。此外，CPT-11 诱导细胞周期停滞在温度敏感的 S 期，脂质 ROS 水平的增加导致 HSP 蛋白表达的降解。这种协同方法可以通过致敏低温PTT以及铁死亡和化疗的联合有效诱导肿瘤细胞死亡。我们的纳米平台还可以最大限度地消灭肿瘤细胞并延长荷瘤小鼠体内的生存时间。这种多功能方法将为低温PTT的临床应用提供更多可能性，并为多种肿瘤治疗的发展提供潜在途径。

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All-in-One Engineering Multifunctional Nanoplatforms for Sensitizing Tumor Low-Temperature Photothermal Therapy In Vivo

Low-temperature photothermal therapy (PTT) is a noninvasive method that harnesses the photothermal effect at low temperatures to selectively eliminate tumor cells, while safeguarding normal tissues, minimizing thermal damage, and enhancing treatment safety. First we evaluated the transcriptome of tumor cells at the gene level following low-temperature treatment and observed significant enrichment of genes involved in cell cycle and heat response-related signaling pathways. To address this challenge, we have developed an engineering multifunctional nanoplatform that offered an all-in-one strategy for efficient sensitization of low-temperature PTT. Specifically, we utilized MoS₂ nanoparticles as the photothermal core to generate low temperature (40–48 °C). The nanoplatform was coated with DPA to load CPT-11 and Fe²⁺ and was further modified with PEG and iRGD to enhance tumor specificity (MoS₂/Fe@CPT-11-PEG-iRGD). Laser- and acid-triggered release of CPT-11 can significantly increase intracellular H₂O₂ content, cooperate with Fe²⁺ ions to increase intracellular lipid ROS content, and activate ferroptosis. Furthermore, CPT-11 induced cell cycle arrest in the temperature-sensitive S-phase, and increased lipid ROS levels contributed to the degradation of HSPs protein expression. This synergistic approach could effectively induce tumor cell death by the sensitized low-temperature PTT and the combination of ferroptosis and chemotherapy. Our nanoplatform can also maximize tumor cell eradication and prolong the survival time of tumor-bearing mice in vivo. The multifunctional approach will provide more possibilities for clinical applications of low-temperature PTT and potential avenues for the development of multiple tumor treatments.

更新日期：2023-10-15

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