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Hyaluronic Acid-Modified Au-Ag Alloy Nanoparticles for Radiation/Nanozyme/Ag+ Multimodal Synergistically Enhanced Cancer Therapy.
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2020-05-28 , DOI: 10.1021/acs.bioconjchem.0c00224
Yu Chong 1, 2 , Jie Huang 2 , Xiaoyu Xu 2 , Chenggong Yu 2 , Xingyu Ning 2 , Saijun Fan 3 , Zhijun Zhang 2
Affiliation  

Gold nanoparticles (AuNPs) have been widely documented as tumor radiosensitizers via enhanced energy deposition of ionizing radiation. However, the sensitization efficiency of AuNPs is still far from satisfactory owing to the irradiation on nontarget tissues and the tumor radio-resistance. To address these issues, we report herein the rational design and development of hyaluronic acid-modified Au–Ag alloy nanoparticles (Au–Ag@HA NPs) with effective tumor radiosensitization by receptor mediated tumor targeting as well as microenvironment-activated hydroxyl radicals (•OH) generation. In our work, Au–Ag@HA NPs were synthesized by the coreduction of HAuCl4 and AgNO3 in the presence of trisodium citrate, followed by surface modification of HA to the Au–Ag alloy NPs. HA modification affords the alloy NPs with specific targeting to 4T1 breast cancer cells overexpressing CD44 receptor, while the introduction of Ag atom imparts the alloy NPs with superior multienzyme-like activities to the monometallic AuNPs for efficient tumor catalytic therapy. More importantly, the ionizing radiation and peroxidase-like activity of Au–Ag@HA NPs boost the production of •OH and the release of toxic Ag+ in the tumor sites, thereby leading to effective tumor therapeutic outcome. This work provides a promising treatment paradigm for radiation/nanozyme/Ag+ combined therapy against cancer and will advance the design and development of multifunctional nanoplatforms for synergetically enhanced tumor therapy.

中文翻译:

透明质酸修饰的Au-Ag合金纳米粒子用于放射/纳米酶/ Ag +多峰协同增强的癌症治疗。

金纳米颗粒(AuNPs)通过增强电离辐射的能量沉积已被广泛证明是肿瘤放射增敏剂。然而,由于在非靶组织上的照射和肿瘤的抗辐射性,AuNPs的敏化效率仍然不能令人满意。为了解决这些问题,我们在此报告了透明质酸修饰的Au-Ag合金纳米粒子(Au-Ag @ HA NPs)的合理设计和开发,该纳米粒子通过受体介导的肿瘤靶向以及微环境激活的羟基自由基(•• OH)生成。在我们的工作中,通过HAuCl 4和AgNO 3的共诱导合成了Au–Ag @ HA NP。在柠檬酸三钠存在下,然后将HA表面修饰成Au-Ag合金NP。HA修饰使合金NPs特异性靶向过表达CD44受体的4T1乳腺癌细胞,而Ag原子的引入赋予合金NPs具有比单金属AuNPs更好的多酶样活性,可用于有效的肿瘤催化治疗。更重要的是,Au–Ag @ HA NPs的电离辐射和类似过氧化物酶的活性促进了•OH的产生以及有毒Ag +在肿瘤部位的释放,从而导致了有效的肿瘤治疗结果。这项工作为放射/纳米酶/银+提供了有希望的治疗范例 联合抗癌疗法,将促进协同增强肿瘤治疗的多功能纳米平台的设计和开发。
更新日期:2020-05-28
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