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Abstract：
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.
摘要：
具有光热剂的化疗药物的自组装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的水溶性差和相互作用差，以驱动自组装纳米载体的形成，这是共同组装的药物/光热剂用于癌症治疗的瓶颈。这里,我们提出了一种基于光热剂和药物化学修饰的自组装化学-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物，它们都具有如此差的水溶性和强烈的自身分子相互作用,以至于它们不能共组装在一起。IR-780用活性靶向配体乳糖酸（LA）修饰以产生两亲性IR780-LA，而CPT通过二硫键修饰成氧化还原敏感的前药CPT-ss-CPT以实现其组装。可以通过IR780-LA和CPT-ss-CPT的共组装来产生明确定义的纳米颗粒(NP)。IR780-LA/CPT-ss-CPT纳米粒子被证明是一种出色的荧光成像引导，氧化还原响应和增强协同化学光热疗法纳米平台抗肿瘤。具体来说,我们的化学修饰策略提供了一种通用的方法来创建自组装的化学光热疗法纳米平台，解决了共组装药物/光热剂用于癌症治疗的瓶颈。重要性声明:具有光热药物的化学治疗剂的自组装纳米颗粒被认为是有趣的化学-光热疗法纳米平台。然而,大多数药物的溶解性和相互作用都很差，无法形成自组装的纳米颗粒。我们提出了一种通用策略，基于常见药物的化学修饰来创建共组装的化学-光热治疗纳米颗粒。IR-780用活性靶向配体LA修饰，产生两亲性IR780-LA分子，而CPT通过二硫键修饰为氧化还原敏感的前药CPT-ss-CPT。明确定义的IR780-LA/CPT-ss-CPT纳米颗粒通过IR780-LA和CPT-ss-CPT的共组装而产生。纳米粒子被证明是一种优异的荧光成像引导，氧化还原响应，主动靶向化学光热治疗纳米平台抗肿瘤。我们的策略提供了一种从常见药物构建智能化学光热治疗纳米平台的通用方法。
