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.

由于光敏剂输送效率低和光的组织穿透性低，使用光动力疗法（PDT）治疗深部癌症受到限制。聚合物纳米载体广泛用于光敏剂递送，而封装光敏剂的自猝灭会损害PDT功效。此外，产生的短寿命活性氧碎片（ROS）很难从纳米载体中扩散出来，导致PDT疗效较低。因此，可以通过光降解并随后激活光敏剂的智能纳米载体系统可以潜在地克服这些限制并增强PDT功效。合成了一种光敏聚合物纳米载体封装光敏剂（RB-M）。开发了一种可顺序传输两种光波长的植入式无线双波长 microLED 设备，以编程方式控制所加载光敏剂的释放和激活。两个具有匹配谐振频率的发射器线圈允许激活连接的 LED 以独立地发射不同的波长。使用基于试剂的数字模拟方法确定最佳照射时间、剂量和 RB-M 浓度。原位大鼠肝癌疾病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可在减少光敏剂和照射剂量的情况下成功实现PDT，这是一个具有临床意义的事件，可提高治疗安全性。