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A versatile strategy to create an active tumor-targeted chemo-photothermal therapy nanoplatform: A case of an IR-780 derivative co-assembled with camptothecin prodrug.
Acta Biomaterialia ( IF 9.7 ) Pub Date : 2018-11-29 , DOI: 10.1016/j.actbio.2018.11.049
Wenxiu He 1 , Yue Jiang 1 , Qian Li 1 , Di Zhang 1 , Zhonghao Li 2 , Yuxia Luan 1
Affiliation  

Self-assembled nanovehicles of chemotherapy drug with photothermal agent are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most of the drugs and photothermal agents have poor water solubility and poor interactions to drive the formation of self-assembled nanovehicles, which is a bottleneck of co-assembled drug/photothermal agent for cancer therapy. Here, we proposed a versatile strategy to create self-assembled chemo-photothermal therapy nanoplatform based on the chemical modification of photothermal agent and drug. The IR-780 and camptothecin (CPT) were chosen as the studied models since they are important photothermal agent and anticancer drug, both of which have such poor water solubility with strong itself molecular interactions that they cannot co-assemble together. IR-780 was modified with an active targeting ligand lactobionic acid (LA) to result in amphiphilic IR780-LA while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through a disulfide linkage to realize its assembly. Well-defined nanoparticles (NPs) could be created through the co-assembling of IR780-LA and CPT-ss-CPT. The IR780-LA/CPT-ss-CPT nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive and enhanced synergistic chemo-photothermal therapy nanoplatform against tumors. Specifically, our chemical modification strategy offers a universal way to create self-assembled chemo-photothermal therapy nanoplatform, which solves the bottleneck of co-assembled drug/photothermal agent for cancer therapy. STATEMENT OF SIGNIFICANCE: Self-assembled nanoparticles of chemotherapeutics with photothermic drugs are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most drugs have too poor solubility and interactions to form into self-assembled nanoparticles. We proposed a versatile strategy to create co-assembled chemo-photothermal therapy nanoparticles based on the chemical modification of common drugs. The IR-780 was modified with an active targeting ligand LA to result in amphiphilic IR780-LA molecules, while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through disulfide linkage. Well-defined IR780-LA/CPT-ss-CPT nanoparticles were created through the co-assembling of IR780-LA and CPT-ss-CPT. The nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive, active targeting chemo-photothermal therapy nanoplatform against tumors. Our strategy offers a versatile way to construct smart chemo-photothermal therapy nanoplatform from common drugs.

中文翻译:

创建活性靶向肿瘤的化学光热疗法纳米平台的通用策略:IR-780衍生物与喜树碱前药共同组装的情况。

具有光热剂的自组装化疗药物纳米载体被认为是有趣的化学光热疗法纳米平台。然而,大多数药物和光热剂具有差的水溶性和不良的相互作用以驱动自组装的纳米载体的形成,这是用于癌症治疗的共组装的药物/光热剂的瓶颈。在这里,我们提出了一种基于光热剂和药物的化学修饰来创建自组装化学光热疗法纳米平台的通用策略。选择IR-780和喜树碱(CPT)作为研究模型,因为它们是重要的光热剂和抗癌药,它们都具有如此差的水溶性,并且本身具有很强的分子相互作用,因此无法共同组装。用活性靶向配体乳糖酸(IR)修饰IR-780,生成两亲性IR780-LA,而CPT通过二硫键修饰成对氧化还原敏感的前药CPT-ss-CPT,以实现其组装。可以通过将IR780-LA和CPT-ss-CPT组装在一起来创建定义明确的纳米粒子(NP)。IR780-LA / CPT-ss-CPT纳米颗粒被证明是一种出色的荧光成像引导,氧化还原响应性和增强的协同化学光热疗法纳米平台,可用于治疗肿瘤。具体而言,我们的化学修饰策略为创建自组装化学光热疗法纳米平台提供了一种通用方法,从而解决了癌症疗法中药物/光热剂共组装的瓶颈。重要性声明:具有光热药物的化学疗法自组装纳米粒子被认为是有趣的化学光热疗法纳米平台。但是,大多数药物的溶解度和相互作用太差,无法形成自组装的纳米颗粒。我们提出了一种通用策略,可以基于普通药物的化学修饰来创建共组装的化学光热疗法纳米颗粒。用活性靶向配体LA修饰IR-780,以产生两亲性IR780-LA分子,而将CPT通过二硫键修饰为氧化还原敏感的前药CPT-ss-CPT。通过IR780-LA和CPT-ss-CPT的共同组装,创建了定义明确的IR780-LA / CPT-ss-CPT纳米粒子。纳米粒子被证明是出色的荧光成像引导,氧化还原响应,积极针对肿瘤的化学光热疗法纳米平台。我们的策略提供了一种从普通药物构建智能化学光热疗法纳米平台的通用方法。
更新日期:2018-11-29
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