In this work, we developed a novel multifunctional nanoplatform based on hyaluronic acid modified Au nanocages (AuNCs-HA). The rational design of AuNCs-HA renders the nanoplatform three functionalities: (1) AuNCs-HA with excellent LSPR peak in the NIR region act as contrast agent for enhanced photoacoustic (PA) imaging and photothermal therapy (PTT); (2) the nanoplatform with high-energy rays (X-ray) absorption and auger electrons generation acts as a radiosensitizer for radiotherapy; (3) good photocatalytic property and large surface area make AuNCs-HA a photosensitive agent for photodynamic therapy (PDT). In vivo results demonstrated that AuNCs-HA presented excellent PA imaging performance after intravenous injection, which provided contour, size, and location information of the tumor. Moreover, because AuNCs-HA could combine radiotherapy and phototherapy together, the tumors treated with AuNCs-HA showed complete growth inhibition, comparing to that with each therapy alone. Taken together, our present study demonstrates that AuNCs-HA is of great potential as a multifunctional nanoplatform for PA imaging-guided radio- and photo-therapy of tumor. STATEMENT OF SIGNIFICANCE: In this study, a commendable theranostic nanoplatform based on hyaluronic acid modified AuNCs (AuNCs-HA) was developed. In our approach, the dilute solution of Gold(III) chloride is slowly dripped into Ag nanocubes solution, then the Au nanocages were obtained by redox reaction, and followed by HA modification. We explored them, simultaneously, as radiosensitizers for RT, photosensitizers for PDT, and therapeutic agents for PTT. Compared to that of each therapies alone, the combination of radio-therapy and photo-therapy results in a considerably improved tumor eliminating effect and efficiently inhibited tumor growth. In addition, AuNCs-HA exhibited remarkably strong PA signals for precise identification of the location, size, and boundary of the tumor, thereby facilitating imaging-guided therapy. In brief, our design of AuNCs-HA represents a general and versatile strategy for building up cancer-targeted nanotheranostics with desired synergistic imaging and therapy functionalities.

中文翻译：

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用于光声成像的多功能纳米热金纳米笼指导放射/光动力/光热协同治疗。

在这项工作中，我们开发了一种基于透明质酸修饰的金纳米笼（AuNCs-HA）的新型多功能纳米平台。AuNCs-HA的合理设计使纳米平台具有三种功能：（1）在NIR区域具有出色LSPR峰的AuNCs-HA用作增强光声（PA）成像和光热疗法（PTT）的造影剂；（2）具有高能射线（X射线）吸收和螺旋钻电子生成的纳米平台可作为放射治疗的放射增敏剂；（3）良好的光催化性能和较大的表面积使AuNCs-HA成为光动力疗法（PDT）的光敏剂。体内结果表明，AuNCs-HA静脉注射后具有出色的PA成像性能，可提供肿瘤的轮廓，大小和位置信息。而且，由于AuNCs-HA可以将放疗和光疗结合在一起，因此与单独使用每种疗法相比，用AuNCs-HA治疗的肿瘤具有完全的生长抑制作用。综上所述，我们目前的研究表明，AuNCs-HA作为多功能纳米平台具有巨大的潜力，可用于PA成像引导的放射线和光疗肿瘤。重大意义声明：在这项研究中，开发了一种值得称赞的基于透明质酸修饰的AuNCs（AuNCs-HA）的治疗学纳米平台。在我们的方法中，将氯化金（III）的稀溶液缓慢滴加到Ag纳米立方体溶液中，然后通过氧化还原反应获得Au纳米笼，然后进行HA修饰。我们同时探索了它们作为RT的放射增敏剂，PDT的光敏剂和PTT的治疗剂。与每种疗法相比，放疗和光疗的结合可显着提高肿瘤清除效果，并有效抑制肿瘤生长。此外，AuNCs-HA表现出非常强的PA信号，可精确识别肿瘤的位置，大小和边界，从而促进影像学指导的治疗。简而言之，我们的AuNCs-HA设计代表了一种通用且通用的策略，可建立具有所需协同成像和治疗功能的靶向癌症的纳米治疗。