近日，新加坡国立大学的Juwita Norasmara Bte Rahmat及其研究小组与香港城市大学的张勇等人合作并取得一项新进展。经过不懈努力，他们实现用于体内编程PDT的无线序贯双光递送。相关研究成果已于2024年5月15日在国际知名学术期刊《光：科学与应用》上发表。

本文合成了一种光敏聚合物纳米载体包封光敏剂(RB-M)。研究人员开发了一种可植入的无线双波长微LED器件，该器件可依次输出两个波长的光，以编程方式控制负载光敏剂的释放和激活。两个具有匹配谐振频率的发射线圈允许激活连接的LED独立发射不同波长。采用基于转换剂的数字模拟方法确定最佳照射时间、剂量和RB-M浓度。原位大鼠肝癌模型的体外和体内验证实验证实，纳米载体破裂和连续低剂量光照射策略在降低光敏剂和照射剂量的情况下成功实现PDT，这是提高治疗安全性的临床重要事件。

据悉，光动力疗法（PDT）在治疗深层癌症时存在局限性，这主要是因为光敏剂的低效递送和光在组织中的穿透能力不足。虽然高分子纳米载体常用于递送光敏剂，但光敏剂在封装后的自猝灭现象会影响其递送效果。另外，生成的短寿命活性氧（ROS）难以从纳米载体中扩散出来，这进一步降低了PDT的效率。因此，开发出一种在光敏剂激活后可被光降解的智能纳米载体系统，有望克服这些限制，提高PDT的效率。

附：英文原文

Title: Wireless sequential dual light delivery for programmed PDT in vivo

Author: Liu, Jiayi, Sun, Bowen, Li, Wenkai, Kim, Han-Joon, Gan, Shu Uin, Ho, John S., Rahmat, Juwita Norasmara Bte, Zhang, Yong

Issue&Volume: 2024-05-15

Abstract: Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

DOI: 10.1038/s41377-024-01437-x

Source: https://www.nature.com/articles/s41377-024-01437-x