MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, China; College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Department of Chemistry and Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration & Reconstruction, Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Kowloon, Hong Kong, China.
Biomaterials. 2018 Sep;176:1-12. doi: 10.1016/j.biomaterials.2018.05.033. Epub 2018 May 21.
Stimuli-responsive nanoparticles are focused to promote the pathological specificity and controlled therapeutic activation in biomedicine, but the multifunctional modulation remains challenging. Herein, size and morphology switchable phototheranostic nanoparticles are developed for photoacoustic (PA) imaging-guided photothermal-chemotherapy. Multifunctional polypyrrole (PPy) nanoparticles with the template of upper critical solution temperature (UCST) polymers are designed to achieve light-controlled pulsatile drug release and concurrent activation of photothermal therapy (PTT). Wherein the UCST-featured inner core is loaded with camptothecin (CPT), the outer corona is tethered with thermo-cleavable doxorubicin (DOX) prodrug and further in-situ coated with PPy, affording the resultant CPT@DOX-UCST/PPy nanoparticles. Upon 808 nm continuous laser illumination, significant heating generated from light-absorbable PPy results in DOX prodrug cleavage and considerable size swelling (∼125-fold), which in turn promotes simultaneous dual drug release, and thus triggering the combined therapeutic activation of PTT and chemotherapy. When laser is switched off, the discontinued photothermal generation makes the nanoparticle shrink back, thereby avoiding the leakage of CPT and DOX. In vivo experiments demonstrate the favorable tumor accumulation and prolonged tumor retention (>24 h) for long-term PA imaging-guided combination therapy. Current multifunctional nanoparticles integrated with light-controlled swelling/shrinking and synergistic therapeutic activation/silence represent a promising platform for precision cancer theranostics.
刺激响应型纳米粒子专注于促进生物医学中的病理学特异性和控制治疗激活，但多功能调节仍然具有挑战性。本文中，开发了尺寸和形态可切换的光热治疗纳米粒子，用于光声（PA）成像引导的光热-化学治疗。设计了具有上临界溶液温度（UCST）聚合物模板的多功能聚吡咯（PPy）纳米粒子，以实现光控脉冲药物释放和光热治疗（PTT）的同时激活。其中，UCST 特征的内核负载喜树碱（CPT），外壳接枝热敏性阿霉素（DOX）前药，并进一步原位包覆 PPy，得到 CPT@DOX-UCST/PPy 纳米粒子。在 808nm 连续激光照射下，可吸收 PPy 产生的显著加热导致 DOX 前药裂解和相当大的尺寸肿胀（约 125 倍），这反过来又促进了双重药物的同时释放，从而触发 PTT 和化学治疗的联合治疗激活。当激光关闭时，停止的光热产生会使纳米粒子收缩，从而避免 CPT 和 DOX 的泄漏。体内实验证明了长时 PA 成像引导联合治疗的良好肿瘤积累和延长的肿瘤保留（>24 小时）。当前的多功能纳米粒子集成了光控膨胀/收缩以及协同治疗激活/沉默，代表了精准癌症治疗学的有前途的平台。
