中国学者PNAS发明抗肿瘤微型“纳米航母”

　　

　近日，中国科学技术大学教授王均课题组与美国Emory大学教授聂书明课题组合作，发明了一种微型“纳米航母”药物递送体系，实现更加精准有效的抗肿瘤药物递送，研究成果发表在《美国科学院院刊》上（PNAS，doi: 10.1073/pnas.1522080113）。论文共同第一作者为王均课题组李洪军、都小姣以及聂书明课题组杜金志。

　　纳米药物递送系统将具有活性的药物分子递送到实体瘤肿瘤细胞的过程中，面临复杂的生物环境和多重生物屏障。小分子化疗药物或者小尺寸药物载体（小于10nm）在血液循环中容易被肾脏过滤快速清除；合适尺寸和表面特性的药物载体（如100nm）能延长药物血液循环，并有效地从肿瘤病理状态下不完整的血管中溢出，但却难以扩散到整个肿瘤组织，无法有效接触肿瘤细胞，导致药物递送的失败。

　　研究人员利用一个较大尺度的纳米载体（约90nm）运载多个小尺度纳米载体（约5nm），并将药物携带在小尺度载体上，形成复合的多级药物输送体系。在其进入血液后，复合结构的纳米载体能够延长药物在血液中的循环时间，并从肿瘤血管中溢出，进入到肿瘤组织。紧接着连接大-小尺度载体的化学键断裂，释放出小尺度载体进一步扩散到整个肿瘤组织，有效地将抗癌药物输送到肿瘤细胞。

　　该研究获得国家重大科学研究计划、国家自然科学基金重大项目、中国科学技术大学“青年创新基金项目”等的资助。

中国科大等发明抗肿瘤微型“纳米航母”

原文摘要：

Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.