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Multifunctional Nanosystem Based on Graphene Oxide for Synergistic Multistage Tumor-Targeting and Combined Chemo-Photothermal Therapy.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-04-03 , DOI: 10.1021/acs.molpharmaceut.8b01335 Huabing Zhang , Yang Li 1, 2 , Zhou Pan , Yilin Chen , Zhongxiong Fan , Haina Tian , Song Zhou 3 , Yubin Zhang , Jiajia Shang , Beili Jiang , Fanfan Wang , Fanghong Luo , Zhenqing Hou
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2019-04-03 , DOI: 10.1021/acs.molpharmaceut.8b01335 Huabing Zhang , Yang Li 1, 2 , Zhou Pan , Yilin Chen , Zhongxiong Fan , Haina Tian , Song Zhou 3 , Yubin Zhang , Jiajia Shang , Beili Jiang , Fanfan Wang , Fanghong Luo , Zhenqing Hou
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Locating nanomedicines at the active sites plays a pivotal role in the nanoparticle-based cancer therapy field. Herein, a multifunctional nanotherapeutic is designed by using graphene oxide (GO) nanosheets with rich carboxyl groups as the supporter for hyaluronic acid (HA)-methotrexate (MTX) prodrug modification via an adipicdihydrazide cross-linker, achieving synergistic multistage tumor-targeting and combined chemo-photothermal therapy. As a tumor-targeting biomaterial, HA can increase affinity of the nanocarrier toward CD44 receptor for enhanced cellular uptake. MTX, a chemotherapeutic agent, can also serve as a tumor-targeting enhancer toward folate receptor based on its similar structure with folic acid. The prepared nanosystems possess a sheet shape with a dynamic size of approximately 200 nm and pH-responsive drug release. Unexpectedly, the physiological stability of HA-MTX prodrug-decorated GO nanosystems in PBS, serum, and even plasma is more excellent than that of HA-decorated GO nanosystems, while both of them exhibit an enhanced photothermal effect than GO nanosheets. More importantly, because of good blood compatibility as well as reduced undesired interactions with blood components, HA-MTX prodrug-decorated GO nanosystems exhibited remarkably superior accumulation at the tumor sites by passive and active targeting mechanisms, achieving highly effective synergistic chemo-photothermal therapeutic effect upon near-infrared laser irradiation, efficient ablation of tumors, and negligible systemic toxicity. Hence, the HA-MTX prodrug-decorated hybrid nanosystems have a promising potential for synergistic multistage tumor-targeting therapy.
中文翻译：
基于氧化石墨烯的多功能纳米系统，用于协同多阶段肿瘤靶向和化学光热疗法的联合。
将纳米药物定位在活性部位在基于纳米颗粒的癌症治疗领域中起着关键作用。在此，通过使用具有丰富羧基的氧化石墨烯（GO）纳米片作为通过己二酰二肼交联剂修饰透明质酸（HA）-甲氨蝶呤（MTX）前药的载体，设计了一种多功能纳米治疗剂，实现了多阶段靶向肿瘤的联合治疗化学光热疗法。作为一种靶向肿瘤的生物材料，HA可以增加纳米载体对CD44受体的亲和力，从而增强细胞摄取。MTX，一种化学治疗剂，由于其与叶酸的相似结构，也可以作为针对叶酸受体的肿瘤靶向增强剂。制备的纳米系统具有片状形状，其动态尺寸约为200 nm，并且具有pH响应型药物释放功能。不料，HA-MTX前体修饰的GO纳米系统在PBS，血清甚至血浆中的生理稳定性要比HA修饰的GO纳米系统的生理稳定性更好，而两者均显示出比GO纳米片增强的光热效应。更重要的是，由于良好的血液相容性以及减少了与血液成分的不良相互作用，HA-MTX前药修饰的GO纳米系统通过被动和主动靶向机制在肿瘤部位表现出显着优越的积累，从而实现了高效的协同化学光热治疗作用。在近红外激光照射下，肿瘤的有效消融和全身毒性可忽略不计。因此，HA-MTX前药修饰的杂交纳米系统具有协同多阶段肿瘤靶向治疗的潜力。
更新日期：2019-03-20
中文翻译：
基于氧化石墨烯的多功能纳米系统，用于协同多阶段肿瘤靶向和化学光热疗法的联合。
将纳米药物定位在活性部位在基于纳米颗粒的癌症治疗领域中起着关键作用。在此，通过使用具有丰富羧基的氧化石墨烯（GO）纳米片作为通过己二酰二肼交联剂修饰透明质酸（HA）-甲氨蝶呤（MTX）前药的载体，设计了一种多功能纳米治疗剂，实现了多阶段靶向肿瘤的联合治疗化学光热疗法。作为一种靶向肿瘤的生物材料，HA可以增加纳米载体对CD44受体的亲和力，从而增强细胞摄取。MTX，一种化学治疗剂，由于其与叶酸的相似结构，也可以作为针对叶酸受体的肿瘤靶向增强剂。制备的纳米系统具有片状形状，其动态尺寸约为200 nm，并且具有pH响应型药物释放功能。不料，HA-MTX前体修饰的GO纳米系统在PBS，血清甚至血浆中的生理稳定性要比HA修饰的GO纳米系统的生理稳定性更好，而两者均显示出比GO纳米片增强的光热效应。更重要的是，由于良好的血液相容性以及减少了与血液成分的不良相互作用，HA-MTX前药修饰的GO纳米系统通过被动和主动靶向机制在肿瘤部位表现出显着优越的积累，从而实现了高效的协同化学光热治疗作用。在近红外激光照射下，肿瘤的有效消融和全身毒性可忽略不计。因此，HA-MTX前药修饰的杂交纳米系统具有协同多阶段肿瘤靶向治疗的潜力。
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