Tumor Microenvironment-Activated and Viral-Mimicking Nanodrugs Driven by Molecular Precise Recognition for dNTP Inhibition-Induced Synergistic Cancer Therapy,ACS Biomaterials Science & Engineering

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Tumor Microenvironment-Activated and Viral-Mimicking Nanodrugs Driven by Molecular Precise Recognition for dNTP Inhibition-Induced Synergistic Cancer Therapy
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-07-10 00:00:00 , DOI: 10.1021/acsbiomaterials.9b00840
Fanfan Wang ₁ , Zhongxiong Fan ₁ , Qixin Zhu ₂ , Haina Tian ₁ , Junyu Yao ₃ , Beili Jiang ₁ , Fukai Zhu ₁ , Guanghao Su ₄ , Zhenqing Hou ₁ , Shefang Ye ₁ , Yang Li _{5,

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Affiliation

The medical application of nanotechnology is promising for cancer chemotherapy. However, most of the small-molecule drug assemblies still have such disadvantages as serious drug leakage and nonideal synergistic mechanisms, resulting in undesired therapeutic effect. Both nucleoside analogue-based clofarabine (CA) and methotrexate (MTX) were used as the first-line anticancer medication. However, a single-agent chemotherapy still faced many challenges including low bioavailability and toxic side effects to normal tissues due to nonspecific biodistribution of drugs. Herein, we designed and fabricated novel viral-mimicking and carry-free nanodrugs (CA-MTX NPs) via molecular recognition-driven precise self-assembly between CA and MTX. After introduction of mild acid-responsive PEG-lipid on the surface of CA-MTX NPs, the synthetic nanodrugs with a diameter of ∼150 nm exhibited tumor microenvironment-activated characteristics and self-targeting property. The results suggested that our nanodrugs could achieve superior tumor accumulation and synergistically promote the tumor suppression by collaboratively inhibiting dNTP pools. We foresaw that the well-designed smart nanodrugs delivery system would open a new avenue in synergistic cancer therapeutics.

中文翻译：

dNTP抑制诱导的协同癌症治疗的分子精确识别驱动的肿瘤微环境激活和模拟病毒的纳米药物。

纳米技术的医学应用有望用于癌症化疗。然而，大多数小分子药物组装体仍具有诸如严重的药物泄漏和不理想的协同机制的缺点，导致不良的治疗效果。基于核苷类似物的氯法拉滨（CA）和甲氨蝶呤（MTX）均被用作一线抗癌药物。然而，由于药物的非特异性生物分布，单药化疗仍面临许多挑战，包括低生物利用度和对正常组织的毒副作用。本文中，我们通过分子识别驱动的CA与MTX之间的精确自组装，设计并制造了新型的模仿病毒和无携带的纳米药物（CA-MTX NP）。在CA-MTX NP的表面引入温和的酸响应性PEG-脂质后，直径约150 nm的合成纳米药物具有肿瘤微环境激活的特性和自靶向特性。结果表明我们的纳米药物可以通过协同抑制dNTP库来实现优异的肿瘤蓄积并协同促进肿瘤抑制。我们预见，精心设计的智能纳米药物输送系统将为协同癌症治疗开辟一条新途径。

更新日期：2019-07-10

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